Tanshinone IIA attenuates heart failure via inhibiting oxidative stress in myocardial infarction rats

Chen,Ruijuan; Chen,Wenli; Huang,Xiaoling; Rui,Qinglin

doi:10.3892/mmr.2021.12043

Tanshinone IIA attenuates heart failure via inhibiting oxidative stress in myocardial infarction rats

Authors:
- Ruijuan Chen
- Wenli Chen
- Xiaoling Huang
- Qinglin Rui
View Affiliations

Affiliations: Emergency Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China, Department of Rehabilitation Medicine, Zhongda Hospital Southeast University, Nanjing, Jiangsu 210009, P.R. China
Published online on: March 26, 2021 https://doi.org/10.3892/mmr.2021.12043
Article Number: 404
Copyright: © Chen 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

The purpose of the present study was to evaluate whether tanshinone IIA (TIIA) could treat cardiac dysfunction and fibrosis in heart failure (HF) by inhibiting oxidative stress. An HF model was induced by ligation of the left anterior descending artery to cause ischemia myocardial infarction (MI) in Sprague‑Dawley rats. Cardiac fibrosis was evaluated using Masson's staining, and the levels of collagen I, collagen III, TGF‑β, α‑smooth muscle actin (α‑SMA), matrix metalloproteinase (MMP) 2 and MMP9 were determined using PCR or western blotting. TIIA treatment reversed the decreases of left ventricular (LV) ejection fraction, fractional shortening (FS), LV systolic pressure and the maximum of the first differentiation of LV pressure (LV ± dp/dt_max), the increases of LV volume in systole, LV volume in diastole, LV end‑systolic diameter and LV end‑diastolic diameter in MI rats. TIIA administration also reversed the increases of expression levels of collagen I, collagen III, TGF‑β, α‑SMA, MMP2 and MMP9 in the heart of MI rats and in angiotensin (Ang) II‑treated cardiac fibroblasts (CFs). TIIA reversed the decreases of superoxide dismutase activity and malondialdehyde and the increases of superoxide anions and NADPH oxidase (Nox) activity in both MI rats and Ang II‑treated CFs. Nox4 overexpression inhibited the effects of TIIA of improving cardiac dysfunction and fibrosis in MI rats and Ang II‑treated CFs. These results demonstrated that TIIA improved cardiac dysfunction and fibrosis via inhibiting oxidative stress in HF rats. Nox4 could regulate the inhibitory effects of TIIA on HF and cardiac fibrosis.

View Figures

View References

1	Bui AL, Horwich TB and Fonarow GC: Epidemiology and risk profile of heart failure. Nat Rev Cardiol. 8:30–41. 2011. View Article : Google Scholar : PubMed/NCBI
2	Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, et al: Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet. 380:2163–2196. 2012. View Article : Google Scholar : PubMed/NCBI
3	Raso A, Dirkx E, Philippen LE, Fernandez-Celis A, De Majo F, Sampaio-Pinto V, Sansonetti M, Juni R, El Azzouzi H, Calore M, et al: Therapeutic Delivery of miR-148a Suppresses Ventricular Dilation in Heart Failure. Mol Ther. 27:584–599. 2019. View Article : Google Scholar : PubMed/NCBI
4	Timmis A, Townsend N, Gale C, Grobbee R, Maniadakis N, Flather M, Wilkins E, Wright L, Vos R, Bax J, et al ESC Scientific Document Group, : European Society of Cardiology: Cardiovascular Disease Statistics 2017. Eur Heart J. 39:508–579. 2018. View Article : Google Scholar : PubMed/NCBI
5	Liu C, Yang CX, Chen XR, Liu BX, Li Y, Wang XZ, Sun W, Li P and Kong XQ: Alamandine attenuates hypertension and cardiac hypertrophy in hypertensive rats. Amino Acids. 50:1071–1081. 2018. View Article : Google Scholar : PubMed/NCBI
6	Wang L, Liu C, Chen X and Li P: Alamandine attenuates long term hypertension induced cardiac fibrosis independent of blood pressure. Mol Med Rep. 19:4553–4560. 2019.PubMed/NCBI
7	Yue Y, Meng K, Pu Y and Zhang X: Transforming growth factor beta (TGF-β) mediates cardiac fibrosis and induces diabetic cardiomyopathy. Diabetes Res Clin Pract. 133:124–130. 2017. View Article : Google Scholar : PubMed/NCBI
8	Yuan X, Pan J, Wen L, Gong B, Li J, Gao H, Tan W, Liang S, Zhang H and Wang X: miR-144-3p Enhances Cardiac Fibrosis After Myocardial Infarction by Targeting PTEN. Front Cell Dev Biol. 7:2492019. View Article : Google Scholar : PubMed/NCBI
9	Rai R, Sun T, Ramirez V, Lux E, Eren M, Vaughan DE and Ghosh AK: Acetyltransferase p300 inhibitor reverses hypertension-induced cardiac fibrosis. J Cell Mol Med. 23:3026–3031. 2019. View Article : Google Scholar : PubMed/NCBI
10	Tan CY, Wong JX, Chan PS, Tan H, Liao D, Chen W, Tan LW, Ackers-Johnson M, Wakimoto H, Seidman JG, et al: Yin Yang 1 Suppresses Dilated Cardiomyopathy and Cardiac Fibrosis Through Regulation of Bmp7 and Ctgf. Circ Res. 125:834–846. 2019. View Article : Google Scholar : PubMed/NCBI
11	Xu QQ, Xu YJ, Yang C, Tang Y, Li L, Cai HB, Hou BN, Chen HF, Wang Q, Shi XG, et al: Sodium Tanshinone IIA Sulfonate Attenuates Scopolamine-Induced Cognitive Dysfunctions via Improving Cholinergic System. BioMed Res Int. 2016:98525362016. View Article : Google Scholar : PubMed/NCBI
12	Li Q, Shen L, Wang Z, Jiang HP and Liu LX: Tanshinone IIA protects against myocardial ischemia reperfusion injury by activating the PI3K/Akt/mTOR signaling pathway. Biomed Pharmacother. 84:106–114. 2016. View Article : Google Scholar : PubMed/NCBI
13	Wang X, Wei Y, Yuan S, Liu G, Lu Y, Zhang J and Wang W: Potential anticancer activity of tanshinone IIA against human breast cancer. Int J Cancer. 116:799–807. 2005. View Article : Google Scholar : PubMed/NCBI
14	Li C, Han X, Zhang H, Wu J and Li B: The interplay between autophagy and apoptosis induced by tanshinone IIA in prostate cancer cells. Tumour Biol. 37:7667–7674. 2016. View Article : Google Scholar : PubMed/NCBI
15	Gao S, Liu Z, Li H, Little PJ, Liu P and Xu S: Cardiovascular actions and therapeutic potential of tanshinone IIA. Atherosclerosis. 220:3–10. 2012. View Article : Google Scholar : PubMed/NCBI
16	Chen FY, Guo R and Zhang BK: Advances in cardiovascular effects of tanshinone II(A). Zhongguo Zhong Yao Za Zhi. 40:1649–1653. 2015.(In Chinese). PubMed/NCBI
17	Sag CM, Santos CX and Shah AM: Redox regulation of cardiac hypertrophy. J Mol Cell Cardiol. 73:103–111. 2014. View Article : Google Scholar : PubMed/NCBI
18	Madamanchi NR and Runge MS: Redox signaling in cardiovascular health and disease. Free Radic Biol Med. 61:473–501. 2013. View Article : Google Scholar : PubMed/NCBI
19	Bonnefont-Rousselot D, Mahmoudi A, Mougenot N, Varoquaux O, Le Nahour G, Fouret P and Lechat P: Catecholamine effects on cardiac remodelling, oxidative stress and fibrosis in experimental heart failure. Redox Rep. 7:145–151. 2002. View Article : Google Scholar : PubMed/NCBI
20	Yan SH, Zhao NW, Geng ZR, Shen JY, Liu FM, Yan D, Zhou J, Nie C, Huang CC and Fang ZY: Modulations of Keap1-Nrf2 signaling axis by TIIA ameliorated the oxidative stress-induced myocardial apoptosis. Free Radic Biol Med. 115:191–201. 2018. View Article : Google Scholar : PubMed/NCBI
21	Gan XB, Duan YC, Xiong XQ, Li P, Cui BP, Gao XY and Zhu GQ: Inhibition of cardiac sympathetic afferent reflex and sympathetic activity by baroreceptor and vagal afferent inputs in chronic heart failure. PLoS One. 6:e257842011. View Article : Google Scholar : PubMed/NCBI
22	Zhang X, Wang Q, Wang X, Chen X, Shao M, Zhang Q, Guo D, Wu Y, Li C, Wang W, et al: Tanshinone IIA protects against heart failure post-myocardial infarction via AMPKs/mTOR-dependent autophagy pathway. Biomed Pharmacother. 112:1085992019. View Article : Google Scholar : PubMed/NCBI
23	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. View Article : Google Scholar : PubMed/NCBI
24	Koshman YE, Patel N, Chu M, Iyengar R, Kim T, Ersahin C, Lewis W, Heroux A and Samarel AM: Regulation of connective tissue growth factor gene expression and fibrosis in human heart failure. J Card Fail. 19:283–294. 2013. View Article : Google Scholar : PubMed/NCBI
25	Hou L, Guo J, Xu F, Weng X, Yue W and Ge J: Cardiomyocyte dimethylarginine dimethylaminohydrolase1 attenuates left-ventricular remodeling after acute myocardial infarction: Involvement in oxidative stress and apoptosis. Basic Res Cardiol. 113:282018. View Article : Google Scholar : PubMed/NCBI
26	Zhang Y, Zhang S and Chen X: Tanshinone IIA protects against cardiac fibrosis through inhibition of β-tubulin expression. J Biol Regul Homeost Agents. 32:1451–1455. 2018.PubMed/NCBI
27	Tsai YT, Loh SH, Lee CY, Lee SP, Chen YL, Cheng TH and Tsai CS: Tanshinone IIA Inhibits High Glucose-Induced Collagen Synthesis via Nuclear Factor Erythroid 2-Related Factor 2 in Cardiac Fibroblasts. Cell Physiol Biochem. 51:2250–2261. 2018. View Article : Google Scholar : PubMed/NCBI
28	Kura B, Szeiffova Bacova B, Kalocayova B, Sykora M and Slezak J: Oxidative Stress-Responsive MicroRNAs in Heart Injury. Int J Mol Sci. 21:3582020. View Article : Google Scholar
29	Kim H, Yun J and Kwon SM: Therapeutic Strategies for Oxidative Stress-Related Cardiovascular Diseases: Removal of Excess Reactive Oxygen Species in Adult Stem Cells. Oxid Med Cell Longev. 2016:24831632016. View Article : Google Scholar : PubMed/NCBI
30	Snezhkina AV, Kudryavtseva AV, Kardymon OL, Savvateeva MV, Melnikova NV, Krasnov GS and Dmitriev AA: ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells. Oxid Med Cell Longev. 2019:61758042019. View Article : Google Scholar : PubMed/NCBI
31	Honda T, Hirakawa Y and Nangaku M: The role of oxidative stress and hypoxia in renal disease. Kidney Res Clin Pract. 38:414–426. 2019. View Article : Google Scholar : PubMed/NCBI
32	Kura B, Szeiffova Bacova B, Kalocayova B, Sykora M and Slezak J: Oxidative Stress-Responsive MicroRNAs in Heart Injury. Int J Mol Sci. 21:3582020. View Article : Google Scholar
33	Chen T, Li M, Fan X, Cheng J and Wang L: Sodium Tanshinone IIA Sulfonate Prevents Angiotensin II–Induced Differentiation of Human Atrial Fibroblasts into Myofibroblasts. Oxid Med Cell Longev. 2018:67125852018. View Article : Google Scholar : PubMed/NCBI
34	Wang P, Zhou S, Xu L, Lu Y, Yuan X, Zhang H, Li R, Fang J and Liu P: Hydrogen peroxide-mediated oxidative stress and collagen synthesis in cardiac fibroblasts: Blockade by tanshinone IIA. J Ethnopharmacol. 145:152–161. 2013. View Article : Google Scholar : PubMed/NCBI
35	Wang P, Wu X, Bao Y, Fang J, Zhou S, Gao J, Pi R, Mou YG and Liu P: Tanshinone IIA prevents cardiac remodeling through attenuating NAD (P)H oxidase-derived reactive oxygen species production in hypertensive rats. Pharmazie. 66:517–524. 2011.PubMed/NCBI
36	Huang L, Zhu J, Zheng M, Zou R, Zhou Y and Zhu M: Tanshinone IIA protects against subclinical lipopolysaccharide induced cardiac fibrosis in mice through inhibition of NADPH oxidase. Int Immunopharmacol. 60:59–63. 2018. View Article : Google Scholar : PubMed/NCBI
37	Wu DM, Wang YJ, Han XR, Wen X, Li L, Xu L, Lu J and Zheng YL: Tanshinone IIA prevents left ventricular remodelling via the TLR4/MyD88/NF-κB signalling pathway in rats with myocardial infarction. J Cell Mol Med. 22:3058–3072. 2018. View Article : Google Scholar : PubMed/NCBI