JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2017, Vol. 55 ›› Issue (5): 13-18.doi: 10.6040/j.issn.1671-7554.0.2016.1378

Previous Articles     Next Articles

Pioglitazone ameliorates cardiac fibrosis induced by hypertension via regulating Sirt3

YAN Fangying, SHAN Xiaolan, LI Jingyuan, ZHANG Jie, YAN Xuefang, YANG Yi, BU Peili   

  1. Department of Cardiology, Qilu Hospital of Shangdong University, Jinan 250012, Shandong, China
  • Received:2016-10-25 Online:2017-05-10 Published:2017-05-10

Abstract: Objective To investigate the effect of pioglitazone on cardiac fibrosis induced by hypertension and the possible mechanism. Methods Cardiac fibroblasts were extracted from newly-born SD rats and divided into 6 groups: negative control group, angiotension II(ANGII 1 μmol/L)group, pioglitazone(Piog 10 μmol/L)group, Piog+ANGII group, Sirt3.siRNA+ANGII group, and Sirt3.siRNA+Piog+ANGII group. The protein expressions of a-SMA, Sirt3, COL I and β-catenin were detected with Western blotting. The mRNA expressions of a-SMA, Sirt3, COL I and β-catenin were detected with quantitative real time PCR. The expression of COL I was evaluated with immuofluorescence staining. Results Compared with the negative control group, the ANGII group showed increased mRNA and protein expressions of a-SMA, COL I and β-catenin, decreased expression of Sirt3, enhanced green fluorescence of COL I, and severer cardiac fibrosis(all P<0.05). Compared with the ANGII group, the Piog+ANGII group 山 东 大 学 学 报 (医 学 版)55卷5期 -严芳英,等.吡格列酮通过调控Sirt3改善高血压引起的心肌纤维化机制 \=-showed increased mRNA and protein expressions of Sirt3, decreased expressions of a-SMA, COL I and β-catenin, lower green fluorescence intensity of COL I, and improved cardiac fibrosis(all P<0.05). Compared with the Piog+ANGII group, the Sirt3.siRNA+Piog+ANGII group showed increased mRNA and protein levels of a-SMA, COL I and β-catenin, decreased levels of Sirt3, and higher green fluorescence intensity of COL I(all P<0.05). However, there were no significant differences in the mRNA and protein expressions between Piog and Piog+ANGII groups(P>0.05), and between Sirt3.siRNA+ANGII and Sirt3. siRNA+Piog+ANGII groups(P>0.05). Conclusion Pioglitazone can improve cardiac fibrosis induced by hypertension via activation of Sirt3 and inhibition of β-catenin.

Key words: Pioglitazone, Hypertension, Cardiac fibrosis, β-catenin, Sirtuin3

CLC Number: 

  • R543.1
[1] Xu T, Liu J, Zhu G, et al. Prevalence of prehypertension and associated risk factors among Chinese adults from a large-scale multi-ethnic population survey[J]. BMC Public Health, 2016, 16(1): 775.
[2] Burchfield JS, Xie M, Hill JA. Pathological ventricular remodeling: mechanisms: part 1 of 2[J]. Circulation, 2013, 128(4): 388-400.
[3] Braunwald E. Heart failure[J]. JACC Heart Fail, 2013, 1(1): 1-20.
[4] Semple RK, Chatterjee VK, ORahilys. PPAR gamma and human metabolic disease[J]. J Clin Invest, 2006, 116(3): 581-589.
[5] Panchapakesan U, Sumual S, Pollock CA, et al. PPARgamma agonists exert antifibrotic effects in renal tubular cells exposed to high glucose[J]. Am J Physiol Renal Physiol, 2005, 289(5): 1153-1158.
[6] Chen T, Li J, Liu J, et al. Activation of SIRT3 by resveratrol ameliorates cardiac fibrosis and improves cardiac function via the TGF-β/Smad3 pathway[J]. Am J Physiol Heart Circ Physiol, 2015, 308(5): 424-434.
[7] Rosenkranz S. TGF-beta1 and angiotensin networking in cardiac remodeling[J]. Cardiovasc Res, 2004, 63(3): 423-432.
[8] 赵红梅, 吴铿. 吡格列酮在抗动脉粥样硬化中的作用[J]. 中国全科医学, 2010, 13(5): 555-557.
[9] Kularni AA, Woeller CF, Thatcher TH, et al. Emerging PPARγ-Independent role of PPARγ ligands in Lung Diseases[J]. PPAR Res, 2012, 705352. doi:10.1155/2012/705352.
[10] Wei WY, Ma ZG, Xu SC, et al. Pioglitazone protected against cardiac hypertrophy via inhibiting AKT/GSK3βand MAPK signaling pathways[J]. PPAR Res, 2016, 9174190. doi: 10.1155/2016/9174190.
[11] Zhao SM, Li HW, Guo CY, et al. Cardiac fibrosis in diabetic rats: regulation and mechanism of activation of PPARamma signal pathway[J]. Chin J Physiol, 2010, 53(4): 262-267.
[12] Nakamura T, Yamamoto E, Kataoka K, et al. Beneficial effects of pioglitazone on hypertensive cardiovascular injury are enhanced by combination with candesartan[J]. Hypertension, 2008, 51(2): 296-301.
[13] Yang Y, Cimen H, Han MJ, et al. NAD+-dependent deacetylase SIRT3 regulates mitochondrial protein synthesis by deacetylation of ribosomal protein MRPL10[J]. J Biol Chen, 2010, 285(10): 7417-7429.
[14] Kim SH, Lu HF, Alano CC. Neuronal SIRT3 protects against exicitotoxic injury in mouse cortical neuron culture[J]. PLoS One, 2011, 6(3): 14731.
[15] Onyango P, Celic I, McCaffery JD, et al. SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localizes to mitochondria[J]. Proc Natl AcadSci USA, 2002, 99(21): 13653-13658.
[16] Bellizzi D, Rose G, Cavalcante P, et al. Anovel VNTR enhancedr within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages[J]. Genomics, 2005, 85(2): 258-263.
[17] Rose G, Data S, Altomare K, et al. Variability of SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly[J]. Exp Gerontol, 2003, 38(10): 1065-1070.
[18] Hafner AV, Dai J, Gomes AP, et al. Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine166 suppresses age-related cardiac hypertrophy[J]. Aging(Albany NY), 2010, 2(12): 914-923.
[19] Pronobis MI, Peifer M. Wnt signaling: The many interfaces of β-catenin[J]. Curr Biol, 2012, 22(4): 137-139.
[20] Villar J, Cabrera NE, Valadares F, et al. Activation of the Wnt/β-catenin signaling pathway by mechanical ventilation is associated with ventilator-induced pulmonary fibrosis in healthy lungs[J]. PLoS One, 2011, 6(9): 23914.
[21] Cuevas CA, Gonzalez AA, Intestrosa NC, et al. Angiotensin II increases fibronectin and collagen I through the β-catenin-dependent signaling in mouse collecting duct cells[J]. Am J Physiol Renal Physiol, 2015, 308(4): 358-365.
[22] Sundaresan NR, Bindu S, Pillai VB, et al. SIRT3 blocks aging-associated tissue fibrosis in mice by deacetylating and activating glycogen synthase kinase 3β[J]. Mol Cell Biol, 2015, 36(5): 678-692.
[1] WUYi-Na, GE Zhi-Ming, LI Fang, HE Hong, JIANG Hong, ZHANG Yun. Expressions of angiotensin converting enzyme 2 mRNA and protein in the kidneys in spontaneously hypertensive rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 5-.
[2] DU Futian, DU Yunlong, LIN Hongfeng. A clinical research on occlusive techniques for partial splentic embolization combined with radiofrequency ablation for hypersplenism due to portal hypertension [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(7): 79-83.
[3] YU Tao, LIU Huanle, FENG Xin, XU Fuyin, CHEN Yafei, XUE Fuzhong, ZHANG Chengqi. A hypertension risk prediction model based on health management cohort [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(6): 61-65.
[4] ZHANG Luan, CHEN Ou, LUAN Yun, ZHU Xiaobo, CHEN Yuan, WANG Yibiao. Effects of gemigliptin on the therapeutic effect and inflammatory factors of monocrotaline-induced pulmonary arterial hypertension in rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(5): 19-22.
[5] LI Rui, MA Weihong, REN Manyi, ZHAO Mengmeng, JIANG Shan, JU Yuanyuan, GUO Ying, SUN Zhaohui, SUI Shujian. Correlation between TWEAK and cardiac remodeling in essential hypertensive patients [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(5): 49-55.
[6] ZHANG Hua, ZHUANG Xia, LIU Zhendong, DIAO Yutao, DU Jiachen, CUI Yi. Evaluation of the effects of high blood pressure on white matter lesion in young adults using diffusion tensor imaging [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(5): 56-60.
[7] XU Tianyi, WU Ping, WANG Ailing, CHEN Liping. Clinical effect of milrinone atomization inhalation on treating severe pneumonia complicated with heart failure of neonates and infants [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(7): 88-90.
[8] WANG Lixuan, ZHANG Lu, XU Xin, LI Sixue, LIU Min, WANG Yaping, MA Huijuan. Chronic intermittent hypobaric hypoxia enhances the vasodilatation of thoracic aorta via PI3K-dependent eNOS activation in rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(2): 11-15.
[9] XI Fuli, ZHANG Mei. Regulation of microRNA-34a on SH2B3 expression during cardiac fibrosis [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(2): 6-10.
[10] PAN Yanyan, SUN Yongchao, ZHAO Cuifen, KONG Qingyu. Clinical efficacy of bosentan in the treatment of babies with congenital heart disease complicated with pulmonary hypertension [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(2): 53-56.
[11] LIU Huimin, LIU Deng, LI Xiaoyu, ZOU Shufeng, JIANG Limin, LI Yuhuan. Effect of Lobelia alkaloids on endothelin-1 signal pathway in a rat model of pulmonary arterial hypertension [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(8): 1-4.
[12] ZHANG Nan, ZHOU Lixiao, SUN Chenglin. Protective effect of riluzole on the damage of rat retina induced by acute intraocular hypertension [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(8): 27-31.
[13] LIU Hui, CHEN Tongshuai, LI Na, WANG Shujian, LI Jingyuan, BU Peili. Role of Sirt3 on the senescence of human umbilical vein endothelial cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(5): 41-45.
[14] TANG Mengmeng, JIN Nüwa, LIU Chuanzhen, LIU Kai, CAO Guangqing, WANG He, PANG Xinyan, WU Shuming. Effects of ethyl pyruvate in the treatment of hyperkinetic pulmonary hypertension [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(5): 75-80.
[15] XU Zhongyang, WANG Liqi, XU Zhenxing, ZHAO Qian, ZHU Shiming. Correlations among RhoA/ROCK signaling pathway, blood pressure variability and carotid artery intima-media thickness in essential hypertensive patients [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(2): 48-51.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!