Exploring novel biomarkers in dilated cardiomyopathy‑induced heart failure by integrated analysis and <em>in vitro</em> experiments

Zhou,Lei; Peng,Fei; Li,Juexing; Gong,Hui

doi:10.3892/etm.2023.12024

Exploring novel biomarkers in dilated cardiomyopathy‑induced heart failure by integrated analysis and in vitro experiments

Authors:
- Lei Zhou
- Fei Peng
- Juexing Li
- Hui Gong
View Affiliations

Affiliations: Department of Cardiology, Jinshan Hospital of Fudan University, Shanghai 201508, P.R. China
Published online on: May 16, 2023 https://doi.org/10.3892/etm.2023.12024
Article Number: 325
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Despite the availability of several effective and promising treatment methods, heart failure (HF) remains a significant public health concern that requires advanced therapeutic strategies and techniques. Dilated cardiomyopathy (DCM) is a crucial factor that contributes to the development and deterioration of HF. The aim of the present study was to identify novel biomarkers and biological pathways to enhance the diagnosis and treatment of patients with DCM‑induced HF using weighted gene co‑expression network analysis (WGCNA). A total of 24 co‑expressed gene modules connected with DCM‑induced HF were obtained by WGCNA. Among these, the blue module had the highest correlation with DCM‑induced HF (r=0.91; P<0.001) and was enriched in the AGE‑RAGE signaling pathway in diabetic complications, the p53 and MAPK signaling pathway, adrenergic signaling in cardiomyocytes, the Janus kinase‑STAT signaling pathway and cGMP/PKG signaling. Eight key genes, including secreted protein acidic and rich in cysteine‑related modular calcium‑binding protein 2 (SMOC2), serpin family A member 3 (SERPINA3), myosin heavy chain 6 (MYH6), S100 calcium binding protein A9 (S100A9), tubulin α (TUBA)3E, TUBA3D, lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1) and phospholipase C ε1 (PLCE1), were selected as the therapeutic targets of DCM‑induced HF based on WGCNA and differentially expressed gene analysis. Immune cell infiltration analysis revealed that the proportion of naive B cells and CD4‑activated memory T cells was markedly upregulated in DCM‑induced HF tissues compared with tissues from healthy controls. Furthermore, reverse transcription‑quantitative PCR in AC16 human cardiomyocyte cells treated with doxorubicin showed that among the eight key genes, only SERPINA3, MYH6, S100A9, LYVE1 and PLCE1 exhibited expression levels identical to those revealed by bioinformatics analysis, suggesting that these genes may be involved in the development of DCM‑induced HF.

View Figures

View References

1	Savarese G and Lund LH: Global public health burden of heart failure. Card Fail Rev. 3:7–11. 2017.PubMed/NCBI View Article : Google Scholar
2	Lumbers RT, Shah S, Lin H, Czuba T, Henry A, Swerdlow DI, Mälarstig A, Andersson C, Verweij N, Holmes MV, et al: The genomics of heart failure: Design and rationale of the HERMES consortium. ESC Heart Fail. 8:5531–5541. 2021.PubMed/NCBI View Article : Google Scholar
3	Ziaeian B and Fonarow GC: Epidemiology and aetiology of heart failure. Nat Rev Cardiol. 13:368–378. 2016.PubMed/NCBI View Article : Google Scholar
4	Smith JG: Molecular epidemiology of heart failure: Translational challenges and opportunities. JACC Basic Transl Sci. 2:757–769. 2017.PubMed/NCBI View Article : Google Scholar
5	Huang J, Yin H, Zhang M, Ni Q and Xuan J: Understanding the economic burden of heart failure in China: Impact on disease management and resource utilization. J Med Econ. 20:549–553. 2017.PubMed/NCBI View Article : Google Scholar
6	Klein S, Jiang S, Morey JR, Pai A, Mancini DM, Lala A and Ferket BS: Estimated health care utilization and expenditures in individuals with heart failure from the medical expenditure panel survey. Circ Heart Fail. 14(e007763)2021.PubMed/NCBI View Article : Google Scholar
7	Yingchoncharoen T, Wu TC, Choi DJ, Ong TK, Liew HB and Cho MC: Economic burden of heart failure in asian countries with different healthcare systems. Korean Circ J. 51:681–693. 2021.PubMed/NCBI View Article : Google Scholar
8	Gomes CPC, Schroen B, Kuster GM, Robinson EL, Ford K, Squire IB, Heymans S, Martelli F, Emanueli C and Devaux Y: EU-CardioRNA COST Action (CA17129). Regulatory RNAs in Heart Failure. Circulation. 141:313–328. 2020.PubMed/NCBI View Article : Google Scholar
9	Guo Q, Zhang Y, Zhang S, Jin J, Pang S, Wu X, Zhang W, Bi X, Zhang Y, Zhang Q and Jiang F: Genome-wide translational reprogramming of genes important for myocyte functions in overload-induced heart failure. Biochim Biophys Acta Mol Basis Dis. 1866(165649)2020.PubMed/NCBI View Article : Google Scholar
10	Pepin ME, Drakos S, Ha CM, Tristani-Firouzi M, Selzman CH, Fang JC, Wende AR and Wever-Pinzon O: DNA methylation reprograms cardiac metabolic gene expression in end-stage human heart failure. Am J Physiol Heart Circ Physiol. 317:H674–H84. 2019.PubMed/NCBI View Article : Google Scholar
11	van der Pol A, Hoes MF, de Boer RA and van der Meer P: Cardiac foetal reprogramming: A tool to exploit novel treatment targets for the failing heart. J Internal Med. 288:491–506. 2020.PubMed/NCBI View Article : Google Scholar
12	Bondue A, Arbustini E, Bianco A, Ciccarelli M, Dawson D, De Rosa M, Hamdani N, Hilfiker-Kleiner D, Meder B, Leite-Moreira AF, et al: Complex roads from genotype to phenotype in dilated cardiomyopathy: Scientific update from the Working Group of Myocardial Function of the European Society of Cardiology. Cardiovasc Res. 114:1287–1303. 2018.PubMed/NCBI View Article : Google Scholar
13	Cannata A, Fabris E, Merlo M, Artico J, Gentile P, Pio Loco C, Ballaben A, Ramani F, Barbati G and Sinagra G: Sex Differences in the Long-term prognosis of dilated cardiomyopathy. Can J Cardiol. 36:37–44. 2020.PubMed/NCBI View Article : Google Scholar
14	Merlo M, Cannata A, Gobbo M, Stolfo D, Elliott PM and Sinagra G: Evolving concepts in dilated cardiomyopathy. Eur J Heart Fail. 20:228–239. 2018.PubMed/NCBI View Article : Google Scholar
15	Jefferies JL and Towbin JA: Dilated cardiomyopathy. Lancet. 375:752–762. 2010.PubMed/NCBI View Article : Google Scholar
16	Clarke R, Peden JF, Hopewell JC, Kyriakou T, Goel A, Heath SC, Parish S, Barlera S, Franzosi MG, Rust S, et al: Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med. 361:2518–2528. 2009.PubMed/NCBI View Article : Google Scholar
17	Kuehl U, Lassner D, Gast M, Stroux A, Rohde M, Siegismund C, Wang X, Escher F, Gross M, Skurk C, et al: Differential Cardiac MicroRNA expression predicts the clinical course in human enterovirus cardiomyopathy. Circ Heart Fail. 8:605–618. 2015.PubMed/NCBI View Article : Google Scholar
18	Roselli C, Chaffin MD, Weng LC, Aeschbacher S, Ahlberg G, Albert CM, Almgren P, Alonso A, Anderson CD, Aragam KG, et al: Multi-ethnic genome-wide association study for atrial fibrillation. Nat Genet. 50:1225–1233. 2018.PubMed/NCBI View Article : Google Scholar
19	Tabibiazar R, Wagner RA, Liao A and Quertermous T: Transcriptional profiling of the heart reveals chamber-specific gene expression patterns. Circ Res. 93:1193–1201. 2003.PubMed/NCBI View Article : Google Scholar
20	Langfelder P and Horvath S: WGCNA: An R package for weighted correlation network analysis. BMC Bioinformatics. 9(559)2008.PubMed/NCBI View Article : Google Scholar
21	To KY: Identification of differential gene expression by high throughput analysis. Comb Chem High Throughput Screen. 3:235–241. 2000.PubMed/NCBI View Article : Google Scholar
22	Dang H, Ye Y, Zhao X and Zeng Y: Identification of candidate genes in ischemic cardiomyopathy by gene expression omnibus database. BMC Cardiovasc Disord. 20(320)2020.PubMed/NCBI View Article : Google Scholar
23	Fan G and Wei J: Identification of potential novel biomarkers and therapeutic targets involved in human atrial fibrillation based on bioinformatics analysis. Kardiologia Polska. 78:694–702. 2020.PubMed/NCBI View Article : Google Scholar
24	Yifan C, Jianfeng S and Jun P: Development and validation of a random forest diagnostic model of acute myocardial infarction based on Ferroptosis-related genes in circulating endothelial cells. Front Cardiovasc Med. 8(663509)2021.PubMed/NCBI View Article : Google Scholar
25	Matkovich SJ, Al Khiami B, Efimov IR, Evans S, Vader J, Jain A, Brownstein BH, Hotchkiss RS and Mann DL: Widespread Down-regulation of cardiac mitochondrial and sarcomeric genes in patients with sepsis. Crit Care Med. 45:407–414. 2017.PubMed/NCBI View Article : Google Scholar
26	Schwientek P, Ellinghaus P, Steppan S, D'Urso D, Seewald M, Kassner A, Cebulla R, Schulte-Eistrup S, Morshuis M, Röfe D, et al: Global gene expression analysis in nonfailing and failing myocardium pre- and postpulsatile and nonpulsatile ventricular assist device support. Physiol Genomics. 42:397–405. 2010.PubMed/NCBI View Article : Google Scholar
27	Sweet ME, Cocciolo A, Slavov D, Jones KL, Sweet JR, Graw SL, Reece TB, Ambardekar AV, Bristow MR, Mestroni L and Taylor MRG: Transcriptome analysis of human heart failure reveals dysregulated cell adhesion in dilated cardiomyopathy and activated immune pathways in ischemic heart failure. BMC Genomics. 19(812)2018.PubMed/NCBI View Article : Google Scholar
28	Yu G, Wang LG, Han Y and He QY: clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS. 16:284–287. 2012.PubMed/NCBI View Article : Google Scholar
29	Chen B, Khodadoust MS, Liu CL, Newman AM and Alizadeh AA: Profiling tumor infiltrating immune cells with CIBERSORT. Methods Mol Biol. 1711:243–259. 2018.PubMed/NCBI View Article : Google Scholar
30	Davidson MM, Nesti C, Palenzuela L, Walker WF, Hernandez E, Protas L, Hirano M and Isaac ND: Novel cell lines derived from adult human ventricular cardiomyocytes. J Mol Cell Cardiol. 39:133–147. 2005.PubMed/NCBI View Article : Google Scholar
31	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
32	Sachinidis A: Cardiotoxicity and heart failure: Lessons from human-induced pluripotent stem cell-derived cardiomyocytes and anticancer drugs. Cells. 9(1001)2020.PubMed/NCBI View Article : Google Scholar
33	Zhong Z, Tian Y, Luo X, Zou J, Wu L and Tian J: Extracellular vesicles derived from human umbilical cord mesenchymal stem cells protect against DOX-induced heart failure through the miR-100-5p/NOX4 pathway. Front Bioeng Biotechnol. 9(703241)2021.PubMed/NCBI View Article : Google Scholar
34	Reichart D, Magnussen C, Zeller T and Blankenberg S: Dilated cardiomyopathy: From epidemiologic to genetic phenotypes: A translational review of current literature. J Internal Med. 286:362–372. 2019.PubMed/NCBI View Article : Google Scholar
35	Weintraub RG, Semsarian C and Macdonald P: Dilated cardiomyopathy. Lancet. 390:400–414. 2017.PubMed/NCBI View Article : Google Scholar
36	Diaz-Navarro R, Urrutia G, Cleland JG, Poloni D, Villagran F, Acosta-Dighero R, Bangdiwala SI, Rada G and Madrid E: Stem cell therapy for dilated cardiomyopathy. Cochrane Database Syst Rev. 7(CD013433)2021.PubMed/NCBI View Article : Google Scholar
37	Haas J, Frese KS, Peil B, Kloos W, Keller A, Nietsch R, Feng Z, Müller S, Kayvanpour E, Vogel B, et al: Atlas of the clinical genetics of human dilated cardiomyopathy. Eur Heart J. 36:1123–1135a. 2015.PubMed/NCBI View Article : Google Scholar
38	Kadhi A, Mohammed F and Nemer G: The genetic pathways underlying immunotherapy in dilated cardiomyopathy. Front Cardiovasc Med. 8(613295)2021.PubMed/NCBI View Article : Google Scholar
39	Merlo M, Pivetta A, Pinamonti B, Stolfo D, Zecchin M, Barbati G, Di Lenarda A and Sinagra G: Long-term prognostic impact of therapeutic strategies in patients with idiopathic dilated cardiomyopathy: Changing mortality over the last 30 years. Eur J Heart Fail. 16:317–324. 2014.PubMed/NCBI View Article : Google Scholar
40	Linde C, Grabowski M, Ponikowski P, Rao I, Stagg A and Tschope C: Cardiac contractility modulation therapy improves health status in patients with heart failure with preserved ejection fraction: A pilot study (CCM-HFpEF). Eur J Heart Fail. 24:2275–2284. 2022.PubMed/NCBI View Article : Google Scholar
41	Liang B, Zhou Z, Yang Z, Liu J, Zhang L, He J, Li H, Huang Y, Yang Q, Xian S and Wang L: AGEs-RAGE axis mediates myocardial fibrosis via activation of cardiac fibroblasts induced by autophagy in heart failure. Exp Physiol. 107:879–891. 2022.PubMed/NCBI View Article : Google Scholar
42	Burr SD and Stewart JA Jr: Extracellular matrix components isolated from diabetic mice alter cardiac fibroblast function through the AGE/RAGE signaling cascade. Life Sci. 250(117569)2020.PubMed/NCBI View Article : Google Scholar
43	Boengler K, Hilfiker-Kleiner D, Drexler H, Heusch G and Schulz R: The myocardial JAK/STAT pathway: From protection to failure. Pharmacol Ther. 120:172–185. 2008.PubMed/NCBI View Article : Google Scholar
44	Okonko DO, Marley SB, Anker SD, Poole-Wilson PA and Gordon MY: Erythropoietin resistance contributes to anaemia in chronic heart failure and relates to aberrant JAK-STAT signal transduction. Int J Cardiol. 164:359–364. 2013.PubMed/NCBI View Article : Google Scholar
45	Terrell AM, Crisostomo PR, Wairiuko GM, Wang M, Morrell ED and Meldrum DR: Jak/STAT/SOCS signaling circuits and associated cytokine-mediated inflammation and hypertrophy in the heart. Shock. 26:226–234. 2006.PubMed/NCBI View Article : Google Scholar
46	Chen SN, Lombardi R, Karmouch J, Tsai JY, Czernuszewicz G, Taylor MRG, Mestroni L, Coarfa C, Gurha P and Marian AJ: DNA damage Response/TP53 pathway is activated and contributes to the pathogenesis of dilated cardiomyopathy associated with LMNA (Lamin A/C) mutations. Circ Res. 124:856–873. 2019.PubMed/NCBI View Article : Google Scholar
47	Das B, Young D, Vasanji A, Gupta S, Sarkar S and Sen S: Influence of p53 in the transition of myotrophin-induced cardiac hypertrophy to heart failure. Cardiovasc Res. 87:524–534. 2010.PubMed/NCBI View Article : Google Scholar
48	Fujita T and Ishikawa Y: Apoptosis in Heart Failure-The role of the beta-adrenergic receptor-mediated signaling pathway and p53-mediated signaling pathway in the apoptosis of cardiomyocytes. Circ J. 75:1811–1818. 2011.PubMed/NCBI View Article : Google Scholar
49	Irie T, Sips PY, Kai S, Kida K, Ikeda K, Hirai S, Moazzami K, Jiramongkolchai P, Bloch DB, Doulias PT, et al: S-Nitrosylation of Calcium-handling proteins in cardiac adrenergic signaling and hypertrophy. Circ Res. 117:793–803. 2015.PubMed/NCBI View Article : Google Scholar
50	Persoon S, Paulus M, Hirt S, Jungbauer C, Dietl A, Luchner A, Schmid C, Maier LS and Birner C: Cardiac unloading by LVAD support differentially influences components of the cGMP-PKG signaling pathway in ischemic and dilated cardiomyopathy. Heart Vessels. 33:948–957. 2018.PubMed/NCBI View Article : Google Scholar
51	Pleger ST, Boucher M, Most P and Koch WJ: Targeting myocardial beta-adrenergic receptor signaling and calcium cycling for heart failure gene therapy. J Card Fail. 13:401–414. 2007.PubMed/NCBI View Article : Google Scholar
52	Port JD and Bristow MR: Altered beta-adrenergic receptor gene regulation and signaling in chronic heart failure. J Mol Cell Cardiol. 33:887–905. 2001.PubMed/NCBI View Article : Google Scholar
53	Razmara E and Garshasbi M: Whole-exome sequencing identifies R1279X of MYH6 gene to be associated with congenital heart disease. BMC Cardiovasc Disord. 18(137)2018.PubMed/NCBI View Article : Google Scholar
54	Carniel E, Taylor MR, Sinagra G, Di Lenarda A, Ku L, Fain PR, Boucek MM, Cavanaugh J, Miocic S, Slavov D, et al: Alpha-myosin heavy chain: A sarcomeric gene associated with dilated and hypertrophic phenotypes of cardiomyopathy. Circulation. 112:54–59. 2005.PubMed/NCBI View Article : Google Scholar
55	Hao E, Zhang G, Mu L, Ma N and Wang T: Establishment of a human MYH6 compound heterozygous knockout hESC line to model cardiomyopathy and congenital heart defects by CRISPR/Cas9 system. Stem Cell Res. 50(102128)2020.PubMed/NCBI View Article : Google Scholar
56	Hershberger RE, Norton N, Morales A, Li D, Siegfried JD and Gonzalez-Quintana J: Coding sequence rare variants identified in MYBPC3, MYH6, TPM1, TNNC1, and TNNI3 from 312 patients with familial or idiopathic dilated cardiomyopathy. Circ Cardiovasc Genet. 3:155–161. 2010.PubMed/NCBI View Article : Google Scholar
57	Merlo M, Sinagra G, Carniel E, Slavov D, Zhu X, Barbati G, Spezzacatene A, Ramani F, Salcedo E, Di Lenarda A, et al: Poor prognosis of rare sarcomeric gene variants in patients with dilated cardiomyopathy. Clin Transl Sci. 6:424–428. 2013.PubMed/NCBI View Article : Google Scholar
58	Chen JH, Wang LL, Tao L, Qi B, Wang Y, Guo YJ and Miao L: Identification of MYH6 as the potential gene for human ischaemic cardiomyopathy. J Cell Mol Med. 25:10736–10746. 2021.PubMed/NCBI View Article : Google Scholar
59	Chelbi ST, Wilson ML, Veillard AC, Ingles SA, Zhang J, Mondon F, Gascoin-Lachambre G, Doridot L, Mignot TM, Rebourcet R, et al: Genetic and epigenetic mechanisms collaborate to control SERPINA3 expression and its association with placental diseases. Hum Mol Genet. 21:1968–1978. 2012.PubMed/NCBI View Article : Google Scholar
60	Asakura M and Kitakaze M: Global gene expression profiling in the failing myocardium. Circ J. 73:1568–1576. 2009.PubMed/NCBI View Article : Google Scholar
61	Delrue L, Vanderheyden M, Beles M, Paolisso P, Di Gioia G, Dierckx R, Verstreken S, Goethals M, Heggermont W and Bartunek J: Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure. ESC Heart Fail. 8:4780–4790. 2021.PubMed/NCBI View Article : Google Scholar
62	di Salvo TG, Yang KC, Brittain E, Absi T, Maltais S and Hemnes A: Right ventricular myocardial biomarkers in human heart failure. J Card Fail. 21:398–411. 2015.PubMed/NCBI View Article : Google Scholar
63	Jiang Z, Guo N and Hong K: A three-tiered integrative analysis of transcriptional data reveals the shared pathways related to heart failure from different aetiologies. J Cell Mol Med. 24:9085–9096. 2020.PubMed/NCBI View Article : Google Scholar
64	Lok SI, van Mil A, Bovenschen N, van der Weide P, van Kuik J, van Wichen D, Peeters T, Siera E, Winkens B, Sluijter JP, et al: Post-transcriptional regulation of α-1-antichymotrypsin by microRNA-137 in chronic heart failure and mechanical support. Circ Heart Fail. 6:853–861. 2013.PubMed/NCBI View Article : Google Scholar
65	Sanchez-Navarro A, Gonzalez-Soria I, Caldino-Bohn R and Bobadilla NA: An integrative view of serpins in health and disease: The contribution of SerpinA3. Am J Physiol Cell Physiol. 320:C106–C108. 2021.PubMed/NCBI View Article : Google Scholar
66	Gerarduzzi C, Kumar RK, Trivedi P, Ajay AK, Iyer A, Boswell S, Hutchinson JN, Waikar SS and Vaidya VS: Silencing SMOC2 ameliorates kidney fibrosis by inhibiting fibroblast to myofibroblast transformation. JCI Insight. 2(e90299)2017.PubMed/NCBI View Article : Google Scholar
67	Williams JL, Cavus O, Loccoh EC, Adelman S, Daugherty JC, Smith SA, Canan B, Janssen PML, Koenig S, Kline CF, et al: Defining the molecular signatures of human right heart failure. Life Sci. 196:118–126. 2018.PubMed/NCBI View Article : Google Scholar
68	Laugier L, Frade AF, Ferreira FM, Baron MA, Teixeira PC, Cabantous S, Ferreira LRP, Louis L, Rigaud VOC, Gaiotto FA, et al: Whole-Genome Cardiac DNA methylation fingerprint and gene expression analysis provide new insights in the pathogenesis of chronic chagas disease cardiomyopathy. Clin Infect Dis. 65:1103–1111. 2017.PubMed/NCBI View Article : Google Scholar
69	Luo L, Wang CC, Song XP, Wang HM, Zhou H, Sun Y, Wang XK, Hou S and Pei FY: Suppression of SMOC2 reduces bleomycin (BLM)-induced pulmonary fibrosis by inhibition of TGF-β1/SMADs pathway. Biomed Pharmacother. 105:841–847. 2018.PubMed/NCBI View Article : Google Scholar
70	Schmidt IM, Colona MR, Kestenbaum BR, Alexopoulos LG, Palsson R, Srivastava A, Liu J, Stillman IE, Rennke HG, Vaidya VS, et al: Cadherin-11, Sparc-related modular calcium binding protein-2, and Pigment epithelium-derived factor are promising non-invasive biomarkers of kidney fibrosis. Kidney Int. 100:672–683. 2021.PubMed/NCBI View Article : Google Scholar
71	McLellan MA, Skelly DA, Dona MSI, Squiers GT, Farrugia GE, Gaynor TL, Cohen CD, Pandey R, Diep H, Vinh A, et al: High-resolution transcriptomic profiling of the heart during chronic stress reveals cellular drivers of cardiac fibrosis and hypertrophy. Circulation. 142:1448–1463. 2020.PubMed/NCBI View Article : Google Scholar
72	Agra RM, Fernandez-Trasancos A, Sierra J, Gonzalez-Juanatey JR and Eiras S: Differential association of S100A9, an inflammatory marker, and p53, a cell cycle marker, expression with epicardial adipocyte size in patients with cardiovascular disease. Inflammation. 37:1504–1512. 2014.PubMed/NCBI View Article : Google Scholar
73	Marinkovic G, Koenis DS, de Camp L, Jablonowski R, Graber N, de Waard V, de Vries CJ, Goncalves I, Nilsson J, Jovinge S and Schiopu A: S100A9 links inflammation and repair in myocardial infarction. Circ Res. 127:664–676. 2020.PubMed/NCBI View Article : Google Scholar
74	Pei XM, Tam BT, Sin TK, Wang FF, Yung BY, Chan LW, Wong CS, Ying M, Lai CW and Siu PM: S100A8 and S100A9 are associated with doxorubicin-induced Cardiotoxicity in the heart of diabetic mice. Front Physiol. 7(334)2016.PubMed/NCBI View Article : Google Scholar
75	Shah RD, Xue C, Zhang H, Tuteja S, Li M, Reilly MP and Ferguson JF: Expression of Calgranulin Genes S100A8, S100A9 and S100A12 Is modulated by n-3 PUFA during inflammation in adipose tissue and mononuclear cells. PLoS One. 12(e0169614)2017.PubMed/NCBI View Article : Google Scholar
76	Wei X, Wu B, Zhao J, Zeng Z, Xuan W, Cao S, Huang X, Asakura M, Xu D, Bin J, et al: Myocardial hypertrophic preconditioning attenuates cardiomyocyte hypertrophy and slows progression to heart failure through upregulation of S100A8/A9. Circulation. 131:1506–1517. 2015.PubMed/NCBI View Article : Google Scholar
77	Marinković G, Koenis DS, de Camp L, Jablonowski R, Graber N, de Waard V, de Vries CJ, Goncalves I, Nilsson J, Jovinge S and Schiopu A: S100A9 links inflammation and repair in myocardial infarction. Circ Res. 127:664–676. 2020.PubMed/NCBI View Article : Google Scholar
78	Marinkovic G, Grauen Larsen H, Yndigegn T, Szabo IA, Mares RG, de Camp L, Weiland M, Tomas L, Goncalves I, Nilsson J, et al: Inhibition of pro-inflammatory myeloid cell responses by short-term S100A9 blockade improves cardiac function after myocardial infarction. Eur Heart J. 40:2713–2723. 2019.PubMed/NCBI View Article : Google Scholar
79	Bizou M, Itier R, Majdoubi M, Abbadi D, Pichery E, Dutaur M, Marsal D, Calise D, Garmy-Susini B, Douin-Echinard V, et al: Cardiac macrophage subsets differentially regulate lymphatic network remodeling during pressure overload. Sci Rep. 11(16801)2021.PubMed/NCBI View Article : Google Scholar
80	Vieira JM, Norman S, Villa Del Campo C, Cahill TJ, Barnette DN, Gunadasa-Rohling M, Johnson LA, Greaves DR, Carr CA, Jackson DG and Riley PR: The cardiac lymphatic system stimulates resolution of inflammation following myocardial infarction. J Clin Invest. 128:3402–3412. 2018.PubMed/NCBI View Article : Google Scholar
81	Chen Y, Wang D, Peng H, Chen X, Han X, Yu J, Wang W, Liang L, Liu Z, Zheng Y, et al: Epigenetically upregulated oncoprotein PLCE1 drives esophageal carcinoma angiogenesis and proliferation via activating the PI-PLCε-NF-κB signaling pathway and VEGF-C/Bcl-2 expression. Mol Cancer. 18(1)2019.PubMed/NCBI View Article : Google Scholar
82	Li W, Li Y, Chu Y, Wu W, Yu Q, Zhu X and Wang Q: PLCE1 promotes myocardial ischemia-reperfusion injury in H/R H9c2 cells and I/R rats by promoting inflammation. Biosci Rep. 39(BSR20181613)2019.PubMed/NCBI View Article : Google Scholar
83	Youn JC, Jung MK, Yu HT, Kwon JS, Kwak JE, Park SH, Kim IC, Park MS, Lee SK, Choi SW, et al: Increased frequency of CD4⁺CD57⁺ senescent T cells in patients with newly diagnosed acute heart failure: Exploring new pathogenic mechanisms with clinical relevance. Sci Rep. 9(12887)2019.PubMed/NCBI View Article : Google Scholar
84	Zeng Z, Wang K, Li Y, Xia N, Nie S, Lv B, Zhang M, Tu X, Li Q, Tang T and Cheng X: Down-regulation of microRNA-451a facilitates the activation and proliferation of CD4⁺ T cells by targeting Myc in patients with dilated cardiomyopathy. J Biol Chem. 292:6004–6013. 2017.PubMed/NCBI View Article : Google Scholar
85	Rao M, Wang X, Guo G, Wang L, Chen S, Yin P, Chen K, Chen L, Zhang Z, Chen X, et al: Resolving the intertwining of inflammation and fibrosis in human heart failure at single-cell level. Basic Res Cardiol. 116(55)2021.PubMed/NCBI View Article : Google Scholar