Glycolysis modulation: New therapeutic strategies to improve pulmonary hypertension (Review)
- Authors:
- Meihong Chen
- Hui Li
- Yun Li
- Yangui Luo
- Yuan He
- Xiaorong Shui
- Wei Lei
-
Affiliations: Guangdong Provincial Engineering Technology Research Center for Molecular Diagnosis and Innovative Drugs Translation of Cardiopulmonary Vascular Diseases, University Joint Laboratory of Guangdong and Macao Region on Molecular Targets and Intervention of Cardiovascular Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China - Published online on: October 16, 2024 https://doi.org/10.3892/ijmm.2024.5439
- Article Number: 115
-
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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Abstract
Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P, et al: 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 61:22008792023. View Article : Google Scholar | |
Jia Z, Wang S, Yan H, Cao Y, Zhang X, Wang L, Zhang Z, Lin S, Wang X and Mao J: Pulmonary vascular remodeling in pulmonary hypertension. J Pers Med. 13:3662023. View Article : Google Scholar : PubMed/NCBI | |
Kang M, Hart CM, Kempker JA, Veeraraghavan S and Trammell AW: Pulmonary hypertension mortality trends in United States 1999-2019. Ann Epidemiol. 75:47–52. 2022. View Article : Google Scholar : PubMed/NCBI | |
Hoeper MM, Humbert M, Souza R, Idrees M, Kawut SM, Sliwa-Hahnle K, Jing ZC and Gibbs JSR: A global view of pulmonary hypertension. Lancet Respir Med. 4:306–322. 2016. View Article : Google Scholar : PubMed/NCBI | |
George MP, Gladwin MT and Graham BB: Exploring new therapeutic pathways in pulmonary hypertension. metabolism, proliferation, and personalized medicine. Am J Respir Cell Mol Biol. 63:279–292. 2020. View Article : Google Scholar : PubMed/NCBI | |
Culley MK and Chan SY: Mitochondrial metabolism in pulmonary hypertension: Beyond mountains there are mountains. J Clin Invest. 128:3704–3715. 2018. View Article : Google Scholar : PubMed/NCBI | |
Smolders VFED, Rodríguez C, Morén C, Blanco I, Osorio J, Piccari L, Bonjoch C, Quax PHA, Peinado VI, Castellà M, et al: Decreased glycolysis as metabolic fingerprint of endothelial cells in chronic thromboembolic pulmonary hypertension. Am J Respir Cell Mol Biol. 63:710–713. 2020. View Article : Google Scholar : PubMed/NCBI | |
Goncharov DA, Kudryashova TV, Ziai H, Ihida-Stansbury K, DeLisser H, Krymskaya VP, Tuder RM, Kawut SM and Goncharova EA: Mammalian target of rapamycin complex 2 (mTORC2) coordinates pulmonary artery smooth muscle cell metabolism, proliferation, and survival in pulmonary arterial hypertension. Circulation. 129:864–874. 2014. View Article : Google Scholar | |
Singh N, Manhas A, Kaur G, Jagavelu K and Hanif K: Inhibition of fatty acid synthase is protective in pulmonary hypertension. Br J Pharmacol. 173:2030–2045. 2016. View Article : Google Scholar : PubMed/NCBI | |
Bertero T, Perk D and Chan SY: The molecular rationale for therapeutic targeting of glutamine metabolism in pulmonary hypertension. Expert Opin Ther Targets. 23:511–524. 2019. View Article : Google Scholar : PubMed/NCBI | |
Hantzidiamantis PJ and Lappin SL: StatPearls; Treasure Island (FL): 2023 | |
Warburg O, Wind F and Negelein E: The metabolism of tumors in the body. J Gen Physiol. 8:519–530. 1927. View Article : Google Scholar : PubMed/NCBI | |
Vaupel P and Multhoff G: Revisiting the Warburg effect: Historical dogma versus current understanding. J Physiol. 599:1745–1757. 2021. View Article : Google Scholar | |
Archer SL: Pyruvate kinase and warburg metabolism in pulmonary arterial hypertension: Uncoupled Glycolysis and the cancer-like phenotype of pulmonary arterial hypertension. Circulation. 136:2486–2490. 2017. View Article : Google Scholar : PubMed/NCBI | |
Archer SL: Acquired mitochondrial abnormalities, including epigenetic inhibition of superoxide dismutase 2, in pulmonary hypertension and cancer: Therapeutic implications. Adv Exp Med Biol. 903:29–53. 2016. View Article : Google Scholar : PubMed/NCBI | |
Vaupel P, Schmidberger H and Mayer A: The Warburg effect: Essential part of metabolic reprogramming and central contributor to cancer progression. Int J Radiat Biol. 95:912–919. 2019. View Article : Google Scholar : PubMed/NCBI | |
Condon D, Agarwal S, Chakraborty A and de Jesus Perez VA: The cancer hypothesis of pulmonary arterial hypertension: The next ten years. Am J Physiol Lung Cell Mol Physiol. 318:L1138–L1139. 2020. View Article : Google Scholar : PubMed/NCBI | |
Christou H and Khalil RA: Mechanisms of pulmonary vascular dysfunction in pulmonary hypertension and implications for novel therapies. Am J Physiol Heart Circ Physiol. 322:H702–H724. 2022. View Article : Google Scholar : PubMed/NCBI | |
Ryanto GRT, Suraya R and Nagano T: Mitochondrial dysfunction in pulmonary hypertension. Antioxidants (Basel). 12:3722023. View Article : Google Scholar : PubMed/NCBI | |
Arai MA, Sakuraba K, Makita Y, Hara Y and Ishibashi M: Evaluation of naturally occurring HIF-1 inhibitors for pulmonary arterial hypertension. Chembiochem. 22:2799–2804. 2021. View Article : Google Scholar : PubMed/NCBI | |
Ahmadi A, Ohira H and Mielniczuk LM: FDG PET imaging for identifying pulmonary hypertension and right heart failure. Curr Cardiol Rep. 17:5552015. View Article : Google Scholar | |
Abikhzer Y, Probst S and Rush C: Pulmonary hypertension findings detected by F-18 FDG PET scan. Clin Nucl Med. 33:405–406. 2008. View Article : Google Scholar : PubMed/NCBI | |
Marsboom G, Wietholt C, Haney CR, Toth PT, Ryan JJ, Morrow E, Thenappan T, Bache-Wiig P, Piao L, Paul J, et al: Lung 18F-fluorodeoxyglucose positron emission tomography for diagnosis and monitoring of pulmonary arterial hypertension. Am J Respir Crit Care Med. 185:670–679. 2012. View Article : Google Scholar : PubMed/NCBI | |
Zhao L, Ashek A, Wang L, Fang W, Dabral S, Dubois O, Cupitt J, Pullamsetti SS, Cotroneo E, Jones H, et al: Heterogeneity in lung (18)FDG uptake in pulmonary arterial hypertension: Potential of dynamic (18)FDG positron emission tomography with kinetic analysis as a bridging biomarker for pulmonary vascular remodeling targeted treatments. Circulation. 128:1214–1224. 2013. View Article : Google Scholar : PubMed/NCBI | |
Caruso P, Dunmore BJ, Schlosser K, Schoors S, Dos Santos C, Perez-Iratxeta C, Lavoie JR, Zhang H, Long L, Flockton AR, et al: Identification of MicroRNA-124 as a major regulator of enhanced endothelial cell glycolysis in pulmonary arterial hypertension via PTBP1 (polypyrimidine tract binding protein) and pyruvate kinase M2. Circulation. 136:2451–2467. 2017. View Article : Google Scholar : PubMed/NCBI | |
Akagi S, Nakamura K, Kondo M, Hirohata S, Udono H, Nishida M, Saito Y, Yoshida M, Miyoshi T and Ito H: Evidence for hypoxia-induced shift in ATP production from glycolysis to mitochondrial respiration in pulmonary artery smooth muscle cells in pulmonary arterial hypertension. J Clin Med. 12:50282023. View Article : Google Scholar : PubMed/NCBI | |
Fijalkowska I, Xu W, Comhair SAA, Janocha AJ, Mavrakis LA, Krishnamachary B, Zhen L, Mao T, Richter A, Erzurum SC and Tuder RM: Hypoxia inducible-factor1alpha regulates the metabolic shift of pulmonary hypertensive endothelial cells. Am J Pathol. 176:1130–1138. 2010. View Article : Google Scholar : PubMed/NCBI | |
Cao Y, Zhang X, Wang L, Yang Q, Ma Q, Xu J, Wang J, Kovacs L, Ayon RJ, Liu Z, et al: PFKFB3-mediated endothelial glycolysis promotes pulmonary hypertension. Proc Natl Acad Sci USA. 116:13394–13403. 2019. View Article : Google Scholar : PubMed/NCBI | |
Boehme J, Sun X, Tormos KV, Gong W, Kellner M, Datar SA, Kameny RJ, Yuan JXJ, Raff GW, Fineman JR, et al: Pulmonary artery smooth muscle cell hyperproliferation and metabolic shift triggered by pulmonary overcirculation. Am J Physiol Heart Circ Physiol. 311:H944–H957. 2016. View Article : Google Scholar : PubMed/NCBI | |
Wujak M, Veith C, Wu CY, Wilke T, Kanbagli ZI, Novoyatleva T, Guenther A, Seeger W, Grimminger F, Sommer N, et al: Adenylate kinase 4-A Key regulator of proliferation and metabolic shift in human pulmonary arterial smooth muscle cells via Akt and HIF-1α signaling pathways. Int J Mol Sci. 22:103712021. View Article : Google Scholar | |
Xu W and Erzurum SC: Endothelial cell energy metabolism, proliferation, and apoptosis in pulmonary hypertension. Compr Physiol. 1:357–372. 2011.PubMed/NCBI | |
Pullamsetti SS, Mamazhakypov A, Weissmann N, Seeger W and Savai R: Hypoxia-inducible factor signaling in pulmonary hypertension. J Clin Invest. 130:5638–5651. 2020. View Article : Google Scholar : PubMed/NCBI | |
Semenza GL: Hypoxia-inducible factors in physiology and medicine. Cell. 148:399–408. 2012. View Article : Google Scholar : PubMed/NCBI | |
Paredes F, Williams HC and San Martin A: Metabolic adaptation in hypoxia and cancer. Cancer Lett. 502:133–142. 2021. View Article : Google Scholar : PubMed/NCBI | |
Yu B, Wang X, Song Y, Xie G, Jiao S, Shi L, Cao X, Han X and Qu A: The role of hypoxia-inducible factors in cardiovascular diseases. Pharmacol Ther. 238:1081862022. View Article : Google Scholar : PubMed/NCBI | |
Mobasheri A, Richardson S, Mobasheri R, Shakibaei M and Hoyland JA: Hypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3: Putative molecular components of the oxygen and glucose sensing apparatus in articular chondrocytes. Histol Histopathol. 20:1327–1338. 2005.PubMed/NCBI | |
Mamun AA, Hayashi H, Yamamura A, Nayeem MJ and Sato M: Hypoxia induces the translocation of glucose transporter 1 to the plasma membrane in vascular endothelial cells. J Physiol Sci. 70:442020. View Article : Google Scholar : PubMed/NCBI | |
Kim JW, Tchernyshyov I, Semenza GL and Dang CV: HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 3:177–185. 2006. View Article : Google Scholar : PubMed/NCBI | |
Menendez MT, Teygong C, Wade K, Florimond C and Blader IJ: siRNA screening identifies the host hexokinase 2 (HK2) gene as an important hypoxia-inducible transcription factor 1 (HIF-1) target gene in toxoplasma gondii-infected cells. mBio. 6:e004622015. View Article : Google Scholar : PubMed/NCBI | |
Cui XG, Han ZT, He SH, Wu XD, Chen TR, Shao CH, Chen DL, Su N, Chen YM, Wang T, et al: HIF1/2α mediates hypoxia-induced LDHA expression in human pancreatic cancer cells. Oncotarget. 8:24840–24852. 2017. View Article : Google Scholar : PubMed/NCBI | |
Samec M, Liskova A, Koklesova L, Mersakova S, Strnadel J, Kajo K, Pec M, Zhai K, Smejkal K, Mirzaei S, et al: Flavonoids targeting HIF-1: Implications on cancer metabolism. Cancers (Basel). 13:1302021. View Article : Google Scholar : PubMed/NCBI | |
Michelakis ED, Gurtu V, Webster L, Barnes G, Watson G, Howard L, Cupitt J, Paterson I, Thompson RB, Chow K, et al: Inhibition of pyruvate dehydrogenase kinase improves pulmonary arterial hypertension in genetically susceptible patients. Sci Transl Med. 9:eaao45832017. View Article : Google Scholar : PubMed/NCBI | |
Chen J, Zhang M, Liu Y, Zhao S, Wang Y, Wang M, Niu W, Jin F and Li Z: Histone lactylation driven by mROS-mediated glycolytic shift promotes hypoxic pulmonary hypertension. J Mol Cell Biol. 14:mjac0732023. View Article : Google Scholar : | |
Cotroneo E, Ashek A, Wang L, Wharton J, Dubois O, Bozorgi S, Busbridge M, Alavian KN, Wilkins MR and Zhao L: Iron homeostasis and pulmonary hypertension: Iron deficiency leads to pulmonary vascular remodeling in the rat. Circ Res. 116:1680–1690. 2015. View Article : Google Scholar : PubMed/NCBI | |
Wedgwood S, Lakshminrusimha S, Schumacker PT and Steinhorn RH: Hypoxia inducible factor signaling and experimental persistent pulmonary hypertension of the newborn. Front Pharmacol. 6:472015. View Article : Google Scholar : PubMed/NCBI | |
Bonnet S, Michelakis ED, Porter CJ, Andrade-Navarro MA, Thébaud B, Bonnet S, Haromy A, Harry G, Moudgil R, McMurtry MS, et al: An abnormal mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: Similarities to human pulmonary arterial hypertension. Circulation. 113:2630–2641. 2006. View Article : Google Scholar : PubMed/NCBI | |
Archer SL, Gomberg-Maitland M, Maitland ML, Rich S, Garcia JGN and Weir EK: Mitochondrial metabolism, redox signaling, and fusion: A mitochondria-ROS-HIF-1alpha-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer. Am J Physiol Heart Circ Physiol. 294:H570–H578. 2008. View Article : Google Scholar | |
Boucherat O, Vitry G, Trinh I, Paulin R, Provencher S and Bonnet S: The cancer theory of pulmonary arterial hypertension. Pulm Circ. 7:285–299. 2017. View Article : Google Scholar : PubMed/NCBI | |
Rhodes CJ, Howard LS, Busbridge M, Ashby D, Kondili E, Gibbs JS, Wharton J and Wilkins MR: Iron deficiency and raised hepcidin in idiopathic pulmonary arterial hypertension: Clinical prevalence, outcomes, and mechanistic insights. J Am Coll Cardiol. 58:300–309. 2011. View Article : Google Scholar : PubMed/NCBI | |
Lanspa SJ, Liu MW and Jenkins HJ Jr: Giant bulla in pneumatosis cystoides intestinalis. J Clin Gastroenterol. 10:437–440. 1988. View Article : Google Scholar : PubMed/NCBI | |
Li M, Liu Y, Jin F, Sun X, Li Z, Liu Y, Fang P, Shi H and Jiang X: Endothelin-1 induces hypoxia inducible factor 1α expression in pulmonary artery smooth muscle cells. FEBS Lett. 586:3888–3893. 2012. View Article : Google Scholar : PubMed/NCBI | |
Alqarni AA, Aldhahir AM, Alghamdi SA, Alqahtani JS, Siraj RA, Alwafi H, AlGarni AA, Majrshi MS, Alshehri SM and Pang L: Role of prostanoids, nitric oxide and endothelin pathways in pulmonary hypertension due to COPD. Front Med (Lausanne). 10:12756842023. View Article : Google Scholar : PubMed/NCBI | |
Jeffrey Man HS, Tsui AKY and Marsden PA: Nitric oxide and hypoxia signaling. Vitam Horm. 96:161–192. 2014. View Article : Google Scholar : PubMed/NCBI | |
Dabral S, Muecke C, Valasarajan C, Schmoranzer M, Wietelmann A, Semenza GL, Meister M, Muley T, Seeger-Nukpezah T, Samakovlis C, et al: A RASSF1A-HIF1α loop drives Warburg effect in cancer and pulmonary hypertension. Nat Commun. 10:21302019. View Article : Google Scholar | |
Siebel C and Lendahl U: Notch signaling in development, tissue homeostasis, and disease. Physiol Rev. 97:1235–1294. 2017. View Article : Google Scholar : PubMed/NCBI | |
Gozlan O and Sprinzak D: Notch signaling in development and homeostasis. Development. 150:dev2011382023. View Article : Google Scholar : PubMed/NCBI | |
Fernández-Chacón M, García-González I, Mühleder S and Benedito R: Role of Notch in endothelial biology. Angiogenesis. 24:237–250. 2021. View Article : Google Scholar : PubMed/NCBI | |
Dabral S, Tian X, Kojonazarov B, Savai R, Ghofrani HA, Weissmann N, Florio M, Sun J, Jonigk D, Maegel L, et al: Notch1 signalling regulates endothelial proliferation and apoptosis in pulmonary arterial hypertension. Eur Respir J. 48:1137–1149. 2016. View Article : Google Scholar : PubMed/NCBI | |
Wang Y, Dai S, Cheng X, Prado E, Yan L, Hu J, He Q, Lv Y, Lv Y and Du L: Notch3 signaling activation in smooth muscle cells promotes extrauterine growth restriction-induced pulmonary hypertension. Nutr Metab Cardiovasc Dis. 29:639–651. 2019. View Article : Google Scholar : PubMed/NCBI | |
Tien PC, Chen X, Elzey BD, Pollock RE and Kuang S: Notch signaling regulates a metabolic switch through inhibiting PGC-1α and mitochondrial biogenesis in dedifferentiated liposarcoma. Oncogene. 42:2521–2535. 2023. View Article : Google Scholar : | |
Landor SKJ, Mutvei AP, Mamaeva V, Jin S, Busk M, Borra R, Grönroos TJ, Kronqvist P, Lendahl U and Sahlgren CM: Hypoand hyperactivated Notch signaling induce a glycolytic switch through distinct mechanisms. Proc Natl Acad Sci USA. 108:18814–18819. 2011. View Article : Google Scholar | |
Sellers K, Allen TD, Bousamra M II, Tan J, Méndez-Lucas A, Lin W, Bah N, Chernyavskaya Y, MacRae JI, Higashi RM, et al: Metabolic reprogramming and Notch activity distinguish between non-small cell lung cancer subtypes. Br J Cancer. 121:51–64. 2019. View Article : Google Scholar : PubMed/NCBI | |
Miyagawa K, Shi M, Chen PI, Hennigs JK, Zhao Z, Wang M, Li CG, Saito T, Taylor S, Sa S, et al: Smooth muscle contact drives endothelial regeneration by BMPR2-Notch1-mediated metabolic and epigenetic changes. Circ Res. 124:211–224. 2019. View Article : Google Scholar : | |
Moriyama H, Moriyama M, Isshi H, Ishihara S, Okura H, Ichinose A, Ozawa T, Matsuyama A and Hayakawa T: Role of notch signaling in the maintenance of human mesenchymal stem cells under hypoxic conditions. Stem Cells Dev. 23:2211–2224. 2014. View Article : Google Scholar : PubMed/NCBI | |
Moriyama H, Moriyama M, Ozawa T, Tsuruta D, Iguchi T, Tamada S, Nakatani T, Nakagawa K and Hayakawa T: Notch signaling enhances stemness by regulating metabolic pathways through modifying p53, NF-κB, and HIF-1α. Stem Cells Dev. 27:935–947. 2018. View Article : Google Scholar : PubMed/NCBI | |
Liu GY and Sabatini DM: mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol. 21:183–203. 2020. View Article : Google Scholar : PubMed/NCBI | |
Saxton RA and Sabatini DM: mTOR signaling in growth, metabolism, and disease. Cell. 169:361–371. 2017. View Article : Google Scholar : PubMed/NCBI | |
Sangüesa G, Roglans N, Baena M, Velázquez AM, Laguna JC and Alegret M: mTOR is a key protein involved in the metabolic effects of simple sugars. Int J Mol Sci. 20:11172019. View Article : Google Scholar : PubMed/NCBI | |
Wang AP, Li XH, Yang YM, Li WQ, Zhang W, Hu CP, Zhang Z and Li YJ: A critical role of the mTOR/eIF2α pathway in hypoxia-induced pulmonary hypertension. PLoS One. 10:e01308062015. View Article : Google Scholar | |
Krymskaya VP, Snow J, Cesarone G, Khavin I, Goncharov DA, Lim PN, Veasey SC, Ihida-Stansbury K, Jones PL and Goncharova EA: mTOR is required for pulmonary arterial vascular smooth muscle cell proliferation under chronic hypoxia. FASEB J. 25:1922–1933. 2011. View Article : Google Scholar : PubMed/NCBI | |
Szwed A, Kim E and Jacinto E: Regulation and metabolic functions of mTORC1 and mTORC2. Physiol Rev. 101:1371–1426. 2021. View Article : Google Scholar : PubMed/NCBI | |
Zhu Y, Shu D, Gong X, Lu M, Feng Q, Zeng XB, Zhang H, Gao J, Guo YW, Liu L, et al: Platelet-derived TGF (transforming growth factor)-β1 enhances the aerobic glycolysis of pulmonary arterial smooth muscle cells by PKM2 (pyruvate kinase muscle isoform 2) upregulation. Hypertension. 79:932–945. 2022. View Article : Google Scholar : PubMed/NCBI | |
Hudson CC, Liu M, Chiang GG, Otterness DM, Loomis DC, Kaper F, Giaccia AJ and Abraham RT: Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Mol Cell Biol. 22:7004–7014. 2002. View Article : Google Scholar : PubMed/NCBI | |
Lu H, Forbes RA and Verma A: Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem. 277:23111–23115. 2002. View Article : Google Scholar : PubMed/NCBI | |
Feng Y and Wu L: mTOR up-regulation of PFKFB3 is essential for acute myeloid leukemia cell survival. Biochem Biophys Res Commun. 483:897–903. 2017. View Article : Google Scholar : PubMed/NCBI | |
Wang C, Jiang J, Ji J, Cai Q, Chen X, Yu Y, Zhu Z and Zhang J: PKM2 promotes cell migration and inhibits autophagy by mediating PI3K/AKT activation and contributes to the malignant development of gastric cancer. Sci Rep. 7:28862017. View Article : Google Scholar : PubMed/NCBI | |
He L, Gomes AP, Wang X, Yoon SO, Lee G, Nagiec MJ, Cho S, Chavez A, Islam T, Yu Y, et al: mTORC1 promotes metabolic reprogramming by the suppression of GSK3-dependent Foxk1 phosphorylation. Mol Cell. 70:949–960.e4. 2018. View Article : Google Scholar : PubMed/NCBI | |
Dodd KM, Yang J, Shen MH, Sampson JR and Tee AR: mTORC1 drives HIF-1α and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3. Oncogene. 34:2239–2250. 2015. View Article : Google Scholar | |
Chi H: Sin1-mTORC2 signaling drives glycolysis of developing thymocytes. J Mol Cell Biol. 11:91–92. 2019. View Article : Google Scholar | |
Lan N, Lu Y, Zhang Y, Pu S, Xi H, Nie X, Liu J and Yuan W: FTO-a common genetic basis for obesity and cancer. Front Genet. 11:5591382020. View Article : Google Scholar | |
Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JRB, Elliott KS, Lango H, Rayner NW, et al: A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 316:889–894. 2007. View Article : Google Scholar : PubMed/NCBI | |
Jia G, Yang CG, Yang S, Jian X, Yi C, Zhou Z and He C: Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO. FEBS Lett. 582:3313–3319. 2008. View Article : Google Scholar : PubMed/NCBI | |
Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y, Yi C, Lindahl T, Pan T, Yang YG and He C: N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol. 7:885–887. 2011. View Article : Google Scholar : PubMed/NCBI | |
Azzam SK, Alsafar H and Sajini AA: FTO m6A demethylase in obesity and cancer: Implications and underlying molecular mechanisms. Int J Mol Sci. 23:38002022. View Article : Google Scholar : PubMed/NCBI | |
Li W, Xing C, Bao L, Han S, Luo T, Wang Z and Fan H: Comprehensive analysis of RNA m6A methylation in pressure overload-induced cardiac hypertrophy. BMC Genomics. 23:5762022. View Article : Google Scholar : PubMed/NCBI | |
Zhang B, Jiang H, Wu J, Cai Y, Dong Z, Zhao Y, Hu Q, Hu K, Sun A and Ge J: m6A demethylase FTO attenuates cardiac dysfunction by regulating glucose uptake and glycolysis in mice with pressure overload-induced heart failure. Signal Transduct Target Ther. 6:3772021. View Article : Google Scholar : PubMed/NCBI | |
Hu L, Wang J, Huang H, Yu Y, Ding J, Yu Y, Li K, Wei D, Ye Q, Wang F, et al: YTHDF1 regulates pulmonary hypertension through translational control of MAGED1. Am J Respir Crit Care Med. 203:1158–1172. 2021. View Article : Google Scholar : PubMed/NCBI | |
Zeng Y, Huang T, Zuo W, Wang D, Xie Y, Wang X, Xiao Z, Chen Z, Liu Q, Liu N and Xiao Y: Integrated analysis of m6A mRNA methylation in rats with monocrotaline-induced pulmonary arterial hypertension. Aging (Albany NY). 13:18238–18256. 2021. View Article : Google Scholar : PubMed/NCBI | |
Liu Y, Wang R, Zhang L, Li J, Lou K and Shi B: The lipid metabolism gene FTO influences breast cancer cell energy metabolism via the PI3K/AKT signaling pathway. Oncol Lett. 13:4685–4690. 2017. View Article : Google Scholar : PubMed/NCBI | |
Liu Y, Liang G, Xu H, Dong W, Dong Z, Qiu Z, Zhang Z, Li F, Huang Y, Li Y, et al: Tumors exploit FTO-mediated regulation of glycolytic metabolism to evade immune surveillance. Cell Metab. 33:1221–1233.e11. 2021. View Article : Google Scholar : PubMed/NCBI | |
Fang YH, Piao L, Hong Z, Toth PT, Marsboom G, Bache-Wiig P, Rehman J and Archer SL: Therapeutic inhibition of fatty acid oxidation in right ventricular hypertrophy: Exploiting Randle's cycle. J Mol Med (Berl). 90:31–43. 2012. View Article : Google Scholar | |
Randle PJ, Priestman DA, Mistry SC and Halsall A: Glucose fatty acid interactions and the regulation of glucose disposal. J Cell Biochem. 55(Suppl 1): S1–S11. 1994. View Article : Google Scholar | |
Archer SL, Fang YH, Ryan JJ and Piao L: Metabolism and bioenergetics in the right ventricle and pulmonary vasculature in pulmonary hypertension. Pulm Circ. 3:144–152. 2013. View Article : Google Scholar : PubMed/NCBI | |
Lee MH, Sanders L, Kumar R, Hernandez-Saavedra D, Yun X, Ford JA, Perez MJ, Mickael C, Gandjeva A, Koyanagi DE, et al: Contribution of fatty acid oxidation to the pathogenesis of pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 323:L355–L371. 2022. View Article : Google Scholar : PubMed/NCBI | |
Mey JT, Hari A, Axelrod CL, Fealy CE, Erickson ML, Kirwan JP, Dweik RA and Heresi GA: Lipids and ketones dominate metabolism at the expense of glucose control in pulmonary arterial hypertension: A hyperglycaemic clamp and metabolomics study. Eur Respir J. 55:19017002020. View Article : Google Scholar : PubMed/NCBI | |
Sutendra G, Bonnet S, Rochefort G, Haromy A, Folmes KD, Lopaschuk GD, Dyck JRB and Michelakis ED: Fatty acid oxidation and malonyl-CoA decarboxylase in the vascular remodeling of pulmonary hypertension. Sci Transl Med. 2:44ra582010. View Article : Google Scholar : PubMed/NCBI | |
Greenberger LM, Horak ID, Filpula D, Sapra P, Westergaard M, Frydenlund HF, Albaek C, Schrøder H and Ørum H: A RNA antagonist of hypoxia-inducible factor-1alpha, EZN-2968, inhibits tumor cell growth. Mol Cancer Ther. 7:3598–3608. 2008. View Article : Google Scholar : PubMed/NCBI | |
Zhao H, Jiang H, Li Z, Zhuang Y, Liu Y, Zhou S, Xiao Y, Xie C, Zhou F and Zhou Y: 2-Methoxyestradiol enhances radiosensitivity in radioresistant melanoma MDA-MB-435R cells by regulating glycolysis via HIF-1α/PDK1 axis. Int J Oncol. 50:1531–1540. 2017. View Article : Google Scholar : PubMed/NCBI | |
Fallah J and Rini BI: HIF inhibitors: Status of current clinical development. Curr Oncol Rep. 21:62019. View Article : Google Scholar : PubMed/NCBI | |
Bruce JY, Eickhoff J, Pili R, Logan T, Carducci M, Arnott J, Treston A, Wilding G and Liu G: A phase II study of 2-methoxyestradiol nanocrystal colloidal dispersion alone and in combination with sunitinib malate in patients with metastatic renal cell carcinoma progressing on sunitinib malate. Invest New Drugs. 30:794–802. 2012. View Article : Google Scholar | |
Jabs M, Rose AJ, Lehmann LH, Taylor J, Moll I, Sijmonsma TP, Herberich SE, Sauer SW, Poschet G, Federico G, et al: Inhibition of endothelial notch signaling impairs fatty acid transport and leads to metabolic and vascular remodeling of the adult heart. Circulation. 137:2592–2608. 2018. View Article : Google Scholar : PubMed/NCBI | |
Chen T, Zhou Q, Tang H, Bozkanat M, Yuan JXJ, Raj JU and Zhou G: miR-17/20 controls prolyl hydroxylase 2 (PHD2)/hypoxia-inducible factor 1 (HIF1) to regulate pulmonary artery smooth muscle cell proliferation. J Am Heart Assoc. 5:e0045102016. View Article : Google Scholar : PubMed/NCBI | |
Wang S, Zeng H, Xie XJ, Tao YK, He X, Roman RJ, Aschner JL and Chen JX: Loss of prolyl hydroxylase domain protein 2 in vascular endothelium increases pericyte coverage and promotes pulmonary arterial remodeling. Oncotarget. 7:58848–58861. 2016. View Article : Google Scholar : PubMed/NCBI | |
Han XJ, Zhang WF, Wang Q, Li M, Zhang CB, Yang ZJ, Tan RJ, Gan LJ, Zhang LL, Lan XM, et al: HIF-1α promotes the proliferation and migration of pulmonary arterial smooth muscle cells via activation of Cx43. J Cell Mol Med. 25:10663–10673. 2021. View Article : Google Scholar : PubMed/NCBI | |
Dessouroux A, Akwa Y and Baulieu EE: DHEA decreases HIF-1alpha accumulation under hypoxia in human pulmonary artery cells: Potential role in the treatment of pulmonary arterial hypertension. J Steroid Biochem Mol Biol. 109:81–89. 2008. View Article : Google Scholar : PubMed/NCBI | |
Ball MK, Waypa GB, Mungai PT, Nielsen JM, Czech L, Dudley VJ, Beussink L, Dettman RW, Berkelhamer SK, Steinhorn RH, et al: Regulation of hypoxia-induced pulmonary hypertension by vascular smooth muscle hypoxia-inducible factor-1α. Am J Respir Crit Care Med. 189:314–324. 2014. View Article : Google Scholar : | |
Docherty CK, Nilsen M and MacLean MR: Influence of 2-methoxyestradiol and sex on hypoxia-induced pulmonary hypertension and hypoxia-inducible factor-1-α. J Am Heart Assoc. 8:e0116282019. View Article : Google Scholar | |
He Y, Fang X, Shi J, Li X, Xie M and Liu X: Apigenin attenuates pulmonary hypertension by inducing mitochondria-dependent apoptosis of PASMCs via inhibiting the hypoxia inducible factor 1α-KV1.5 channel pathway. Chem Biol Interact. 317:1089422020. View Article : Google Scholar | |
Jiang Y, Zhou Y, Peng G, Liu N, Tian H, Pan D, Liu L, Yang X, Li C, Li W, et al: Topotecan prevents hypoxia-induced pulmonary arterial hypertension and inhibits hypoxia-inducible factor-1α and TRPC channels. Int J Biochem Cell Biol. 104:161–170. 2018. View Article : Google Scholar : PubMed/NCBI | |
Koulmann N, Novel-Chaté V, Peinnequin A, Chapot R, Serrurier B, Simler N, Richard H, Ventura-Clapier R and Bigard X: Cyclosporin A inhibits hypoxia-induced pulmonary hypertension and right ventricle hypertrophy. Am J Respir Crit Care Med. 174:699–705. 2006. View Article : Google Scholar : PubMed/NCBI | |
Kurosawa R, Satoh K, Kikuchi N, Kikuchi H, Saigusa D, Al-Mamun ME, Siddique MAH, Omura J, Satoh T, Sunamura S, et al: Identification of celastramycin as a novel therapeutic agent for pulmonary arterial hypertension. Circ Res. 125:309–327. 2019. View Article : Google Scholar : PubMed/NCBI | |
Abud EM, Maylor J, Undem C, Punjabi A, Zaiman AL, Myers AC, Sylvester JT, Semenza GL and Shimoda LA: Digoxin inhibits development of hypoxic pulmonary hypertension in mice. Proc Natl Acad Sci USA. 109:1239–1244. 2012. View Article : Google Scholar : PubMed/NCBI | |
Kovacs L, Cao Y, Han W, Meadows L, Kovacs-Kasa A, Kondrikov D, Verin AD, Barman SA, Dong Z, Huo Y and Su Y: PFKFB3 in smooth muscle promotes vascular remodeling in pulmonary arterial hypertension. Am J Respir Crit Care Med. 200:617–627. 2019. View Article : Google Scholar : PubMed/NCBI | |
Jiang L, Goncharov DA, Shen Y, Lin D, Chang B, Pena A, DeLisser H, Goncharova EA and Kudryashova TV: Akt-dependent glycolysis-driven lipogenesis supports proliferation and survival of human pulmonary arterial smooth muscle cells in pulmonary hypertension. Front Med (Lausanne). 9:8868682022. View Article : Google Scholar : PubMed/NCBI | |
Yan N: A glimpse of membrane transport through structures-advances in the structural biology of the GLUT glucose transporters. J Mol Biol. 429:2710–2725. 2017. View Article : Google Scholar : PubMed/NCBI | |
Thorens B and Mueckler M: Glucose transporters in the 21st century. Am J Physiol Endocrinol Metab. 298:E141–E145. 2010. View Article : Google Scholar : | |
Ismail A and Tanasova M: Importance of GLUT transporters in disease diagnosis and treatment. Int J Mol Sci. 23:86982022. View Article : Google Scholar : PubMed/NCBI | |
Broderick TL and King TM: Upregulation of GLUT-4 in right ventricle of rats with monocrotaline-induced pulmonary hypertension. Med Sci Monit. 14:BR261–BR264. 2008.PubMed/NCBI | |
Li W, Chen W, Peng H, Xiao Z, Liu J, Zeng Y, Huang T, Song Q, Wang X and Xiao Y: Shikonin improves pulmonary vascular remodeling in monocrotaline-induced pulmonary arterial hypertension via regulation of PKM2. Mol Med Rep. 27:602023. View Article : Google Scholar | |
Liu A, Li B, Yang M, Shi Y and Su J: Targeted treprostinil delivery inhibits pulmonary arterial remodeling. Eur J Pharmacol. 923:1747002022. View Article : Google Scholar : PubMed/NCBI | |
Chowdhury B, Luu AZ, Luu VZ, Kabir MG, Pan Y, Teoh H, Quan A, Sabongui S, Al-Omran M, Bhatt DL, et al: The SGLT2 inhibitor empagliflozin reduces mortality and prevents progression in experimental pulmonary hypertension. Biochem Biophys Res Commun. 524:50–56. 2020. View Article : Google Scholar : PubMed/NCBI | |
Tang Y, Tan S, Li M, Tang Y, Xu X, Zhang Q, Fu Q, Tang M, He J, Zhang Y, et al: Dapagliflozin, sildenafil and their combination in monocrotaline-induced pulmonary arterial hypertension. BMC Pulm Med. 22:1422022. View Article : Google Scholar : PubMed/NCBI | |
Kayano H, Koba S, Hirano T, Matsui T, Fukuoka H, Tsuijita H, Tsukamoto S, Hayashi T, Toshida T, Watanabe N, et al: Dapagliflozin influences ventricular hemodynamics and exercise-induced pulmonary hypertension in type 2 diabetes patients-a randomized controlled trial. Circ J. 84:1807–1817. 2020. View Article : Google Scholar : PubMed/NCBI | |
Zapater JL, Lednovich KR, Khan MW, Pusec CM and Layden BT: Hexokinase domain-containing protein-1 in metabolic diseases and beyond. Trends Endocrinol Metab. 33:72–84. 2022. View Article : Google Scholar | |
Wilson JE: Isozymes of mammalian hexokinase: Structure, subcellular localization and metabolic function. J Exp Biol. 206:2049–2057. 2003. View Article : Google Scholar : PubMed/NCBI | |
Chen F, Wang H, Lai J, Cai S and Yuan L: 3-Bromopyruvate reverses hypoxia-induced pulmonary arterial hypertension through inhibiting glycolysis: In vitro and in vivo studies. Int J Cardiol. 266:236–241. 2018. View Article : Google Scholar : PubMed/NCBI | |
Zhang YL, Zhang R, Shen YF, Huang KY, He YY, Zhao JH and Jing ZC: 3-Bromopyruvate attenuates experimental pulmonary hypertension via inhibition of glycolysis. Am J Hypertens. 32:426–432. 2019. View Article : Google Scholar | |
Liu J, Wang W, Wang L, Qi XM, Sha YH and Yang T: 3-Bromopyruvate alleviates the development of monocrotaline-induced rat pulmonary arterial hypertension by decreasing aerobic glycolysis, inducing apoptosis, and suppressing inflammation. Chin Med J (Engl). 133:49–60. 2020. View Article : Google Scholar : PubMed/NCBI | |
Gao S, Chen X, Jin H, Ren S, Liu Z, Fang X and Zhang G: Overexpression of ErbB2 renders breast cancer cells susceptible to 3-BrPA through the increased dissociation of hexokinase II from mitochondrial outer membrane. Oncol Lett. 11:1567–1573. 2016. View Article : Google Scholar : PubMed/NCBI | |
Mathupala SP, Ko YH and Pedersen PL: Hexokinase II: Cancer's double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene. 25:4777–4786. 2006. View Article : Google Scholar : PubMed/NCBI | |
Pajak B, Siwiak E, Sołtyka M, Priebe A, Zieliński R, Fokt I, Ziemniak M, Jaśkiewicz A, Borowski R, Domoradzki T and Priebe W: 2-Deoxy-d-glucose and its analogs: From diagnostic to therapeutic agents. Int J Mol Sci. 21:2342019. View Article : Google Scholar | |
Laussel C and Léon S: Cellular toxicity of the metabolic inhibitor 2-deoxyglucose and associated resistance mechanisms. Biochem Pharmacol. 182:1142132020. View Article : Google Scholar : PubMed/NCBI | |
Lu Y, Chen R, Ma JY, Wang LP, Qiu LL, Wang CP, Yan JC and Liu PJ: Platelet derived growth factor-BB regulates phenotype transformation of pulmonary artery smooth muscle cells via SIRT3 affecting glycolytic pathway. Zhonghua Xin Xue Guan Bing Za Zhi. 47:993–999. 2019.In Chinese. PubMed/NCBI | |
Maier A, Liao SL, Lescure T, Robson PM, Hirata N, Sartori S, Narula N, Vergani V, Soultanidis G, Morgenthau A, et al: Pulmonary artery 18F-fluorodeoxyglucose uptake by PET/CMR as a marker of pulmonary hypertension in sarcoidosis. JACC Cardiovasc Imaging. 15:108–120. 2022. View Article : Google Scholar | |
Frille A, Steinhoff KG, Hesse S, Grachtrup S, Wald A, Wirtz H, Sabri O and Seyfarth HJ: Thoracic [18F]fluorodeoxyglucose uptake measured by positron emission tomography/computed tomography in pulmonary hypertension. Medicine (Baltimore). 95:e39762016. View Article : Google Scholar : PubMed/NCBI | |
Van Schaftingen E, Jett MF, Hue L and Hers HG: Control of liver 6-phosphofructokinase by fructose 2,6-bisphosphate and other effectors. Proc Natl Acad Sci USA. 78:3483–3486. 1981. View Article : Google Scholar : PubMed/NCBI | |
Rider MH, Bertrand L, Vertommen D, Michels PA, Rousseau GG and Hue L: 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: Head-to-head with a bifunctional enzyme that controls glycolysis. Biochem J. 381:561–579. 2004. View Article : Google Scholar : PubMed/NCBI | |
Wang L, Zhang X, Cao Y, Ma Q, Mao X, Xu J, Yang Q, Zhou Y, Lucas R, Fulton DJ, et al: Mice with a specific deficiency of Pfkfb3 in myeloid cells are protected from hypoxia-induced pulmonary hypertension. Br J Pharmacol. 178:1055–1072. 2021. View Article : Google Scholar | |
Zahra K, Dey T, Ashish, Mishra SP and Pandey U: Pyruvate kinase M2 and cancer: The role of PKM2 in promoting tumorigenesis. Front Oncol. 10:1592020. View Article : Google Scholar : PubMed/NCBI | |
Dasgupta A, Wu D, Tian L, Xiong PY, Dunham-Snary KJ, Chen KH, Alizadeh E, Motamed M, Potus F, Hindmarch CCT and Archer SL: Mitochondria in the pulmonary vasculature in health and disease: Oxygen-sensing, metabolism, and dynamics. Compr Physiol. 10:713–765. 2020. View Article : Google Scholar : PubMed/NCBI | |
Shimauchi T, Boucherat O, Yokokawa T, Grobs Y, Wu W, Orcholski M, Martineau S, Omura J, Tremblay E, Shimauchi K, et al: PARP1-PKM2 axis mediates right ventricular failure associated with pulmonary arterial hypertension. JACC Basic Transl Sci. 7:384–403. 2022. View Article : Google Scholar : PubMed/NCBI | |
Arora S, Joshi G, Chaturvedi A, Heuser M, Patil S and Kumar R: A perspective on medicinal chemistry approaches for targeting pyruvate kinase M2. J Med Chem. 65:1171–1205. 2022. View Article : Google Scholar | |
Chhipa AS and Patel S: Targeting pyruvate kinase muscle isoform 2 (PKM2) in cancer: What do we know so far? Life Sci. 280:1196942021. View Article : Google Scholar : PubMed/NCBI | |
Hua Q, Mi B, Xu F, Wen J, Zhao L, Liu J and Huang G: Hypoxia-induced lncRNA-AC020978 promotes proliferation and glycolytic metabolism of non-small cell lung cancer by regulating PKM2/HIF-1α axis. Theranostics. 10:4762–4778. 2020. View Article : Google Scholar : | |
Chen D, Wei L, Liu ZR, Yang JJ, Gu X, Wei ZZ, Liu LP and Yu SP: Pyruvate kinase M2 increases angiogenesis, neurogenesis, and functional recovery mediated by upregulation of STAT3 and focal adhesion kinase activities after ischemic stroke in adult mice. Neurotherapeutics. 15:770–784. 2018. View Article : Google Scholar : PubMed/NCBI | |
Pei L, Le Y, Chen H, Feng J, Liu Z, Zhu J, Wang C, Chen L, Dou X and Lu D: Cynaroside prevents macrophage polarization into pro-inflammatory phenotype and alleviates cecal ligation and puncture-induced liver injury by targeting PKM2/HIF-1α axis. Fitoterapia. 152:1049222021. View Article : Google Scholar | |
Xiong PY, Motamed M, Chen KH, Dasgupta A, Potus F, Tian L, Martin A, Mewburn J, Jones O, Thébaud A and Archer SL: Inhibiting pyruvate kinase muscle isoform 2 regresses group 2 pulmonary hypertension induced by supra-coronary aortic banding. Acta Physiol (Oxf). 234:e137642022. View Article : Google Scholar : PubMed/NCBI | |
Piao L, Sidhu VK, Fang YH, Ryan JJ, Parikh KS, Hong Z, Toth PT, Morrow E, Kutty S, Lopaschuk GD and Archer SL: FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 (PDK4) decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension: Therapeutic benefits of dichloroacetate. J Mol Med (Berl). 91:333–346. 2013. View Article : Google Scholar | |
Michelakis ED, McMurtry MS, Wu XC, Dyck JRB, Moudgil R, Hopkins TA, Lopaschuk GD, Puttagunta L, Waite R and Archer SL: Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats: Role of increased expression and activity of voltage-gated potassium channels. Circulation. 105:244–250. 2002. View Article : Google Scholar : PubMed/NCBI | |
McMurtry MS, Bonnet S, Wu X, Dyck JRB, Haromy A, Hashimoto K and Michelakis ED: Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ Res. 95:830–840. 2004. View Article : Google Scholar : PubMed/NCBI | |
Guignabert C, Tu L, Izikki M, Dewachter L, Zadigue P, Humbert M, Adnot S, Fadel E and Eddahibi S: Dichloroacetate treatment partially regresses established pulmonary hypertension in mice with SM22alpha-targeted overexpression of the serotonin transporter. FASEB J. 23:4135–4147. 2009. View Article : Google Scholar : PubMed/NCBI | |
Ciapponi A, Pizarro R and Harrison J: WITHDRAWN: Trimetazidine for stable angina. Cochrane Database Syst Rev. 3:CD0036142017.PubMed/NCBI | |
Wu Z, Yu L and Li X and Li X: Protective mechanism of trimetazidine in myocardial cells in myocardial infarction rats through ERK signaling pathway. Biomed Res Int. 2021:99245492021. View Article : Google Scholar : PubMed/NCBI | |
Ferrari R, Ford I, Fox K, Challeton JP, Correges A, Tendera M, Widimský P and Danchin N; ATPCI investigators: Efficacy and safety of trimetazidine after percutaneous coronary intervention (ATPCI): A randomised, double-blind, placebo-controlled trial. Lancet. 396:830–838. 2020. View Article : Google Scholar : PubMed/NCBI | |
Shu H, Peng Y, Hang W, Zhou N and Wang DW: Trimetazidine in heart failure. Front Pharmacol. 11:5691322021. View Article : Google Scholar : PubMed/NCBI | |
Parra V, Bravo-Sagua R, Norambuena-Soto I, Hernández-Fuentes CP, Gómez-Contreras AG, Verdejo HE, Mellado R, Chiong M, Lavandero S and Castro PF: Inhibition of mitochondrial fission prevents hypoxia-induced metabolic shift and cellular proliferation of pulmonary arterial smooth muscle cells. Biochim Biophys Acta Mol Basis Dis. 1863:2891–2903. 2017. View Article : Google Scholar : PubMed/NCBI | |
Dobbins RL, Szczepaniak LS, Bentley B, Esser V, Myhill J and McGarry JD: Prolonged inhibition of muscle carnitine palmitoyltransferase-1 promotes intramyocellular lipid accumulation and insulin resistance in rats. Diabetes. 50:123–130. 2001. View Article : Google Scholar : PubMed/NCBI | |
Leamy AK, Egnatchik RA and Young JD: Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease. Prog Lipid Res. 52:165–174. 2013. View Article : Google Scholar | |
Ma Y, Temkin SM, Hawkridge AM, Guo C, Wang W, Wang XY and Fang X: Fatty acid oxidation: An emerging facet of metabolic transformation in cancer. Cancer Lett. 435:92–100. 2018. View Article : Google Scholar : PubMed/NCBI | |
Verdejo HE, Rojas A, López-Crisosto C, Baraona F, Gabrielli L, Maracaja-Coutinho V, Chiong M, Lavandero S and Castro PF: Effects of trimetazidine on right ventricular function and ventricular remodeling in patients with pulmonary artery hypertension: A randomised controlled trial. J Clin Med. 12:15712023. View Article : Google Scholar : PubMed/NCBI | |
Cavallino C, Facchini M, Veia A, Bacchni S, Rosso R, Rognoni A, Rametta F, Lupi A and Bongo AS: New anti-anginal drugs: Ranolazine. Cardiovasc Hematol Agents Med Chem. 13:14–20. 2015. View Article : Google Scholar | |
McKelvey KJ, Wilson EB, Short S, Melcher AA, Biggs M, Diakos CI and Howell VM: Glycolysis and fatty acid oxidation inhibition improves survival in glioblastoma. Front Oncol. 11:6332102021. View Article : Google Scholar : PubMed/NCBI | |
McCormack JG, Barr RL, Wolff AA and Lopaschuk GD: Ranolazine stimulates glucose oxidation in normoxic, ischemic, and reperfused ischemic rat hearts. Circulation. 93:135–142. 1996. View Article : Google Scholar : PubMed/NCBI | |
Clarke B, Wyatt KM and McCormack JG: Ranolazine increases active pyruvate dehydrogenase in perfused normoxic rat hearts: Evidence for an indirect mechanism. J Mol Cell Cardiol. 28:341–350. 1996. View Article : Google Scholar : PubMed/NCBI | |
Han QJ, Forfia P, Vaidya A, Ramani G, deKemp RA, Mach RH, Mankoff DA, Bravo PE, DiCarli M, Chan SY, et al: Effects of ranolazine on right ventricular function, fluid dynamics, and metabolism in patients with precapillary pulmonary hypertension: Insights from a longitudinal, randomized, double-blinded, placebo controlled, multicenter study. Front Cardiovasc Med. 10:11187962023. View Article : Google Scholar : PubMed/NCBI | |
Wu J, Liu T, Shi S, Fan Z, Hiram R, Xiong F, Cui B, Su X, Chang R, Zhang W, et al: Dapagliflozin reduces the vulnerability of rats with pulmonary arterial hypertension-induced right heart failure to ventricular arrhythmia by restoring calcium handling. Cardiovasc Diabetol. 21:1972022. View Article : Google Scholar : PubMed/NCBI | |
Luo L, Xiao L, Lian G, Wang H and Xie L: miR-125a-5p inhibits glycolysis by targeting hexokinase-II to improve pulmonary arterial hypertension. Aging (Albany NY). 12:9014–9030. 2020. View Article : Google Scholar : PubMed/NCBI | |
Kassa B, Kumar R, Mickael C, Sanders L, Vohwinkel C, Lee MH, Gu S, Poth JM, Stenmark KR, Zhao YY, et al: Endothelial cell PHD2-HIF1α-PFKFB3 contributes to right ventricle vascular adaptation in pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 321:L675–L685. 2021. View Article : Google Scholar | |
Qi L, Lv T, Cheng Y, Yu M, Han H, Kong H, Xie W, Wang H, Zhang Y and Huang Z: Fasudil dichloroacetate (FDCA), an orally available agent with potent therapeutic efficiency on monocrotaline-induced pulmonary arterial hypertension rats. Bioorg Med Chem Lett. 29:1812–1818. 2019. View Article : Google Scholar : PubMed/NCBI |