Simvastatin ameliorates ventricular remodeling via the TGF-β1 signaling pathway in rats following myocardial infarction

Xiao, X.H.; Chang, Guanglei; Liu, Jian; Sun, Guangyun; Liu, Li; Shu, Qin; Zhang, Dongying

doi:10.3892/mmr.2016.5178

Cited by 27 publications

(19 citation statements)

References 25 publications

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“…Smad2/3 is one of the main downstream effectors of TGF- β 1 [ 37 ]. Previous studies have reported that inhibition of TGF- β 1/Smad2/3 signaling effectively protects against cardiomyocyte apoptosis and detrimental ventricular remodeling [ 37 – 39 ]. The in vitro experiment also suggested that the increased production of collagen I and collagen III as well as excessive proliferation of CFs induced by Ang II was attenuated through suppression of TGF- β /Smad signaling [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Flavonoid Extract from Propolis Inhibits Cardiac Fibrosis Triggered by Myocardial Infarction through Upregulation of SIRT1

Wang

Sui

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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The flavonoid extract from propolis (FP) has been shown to protect against heart injury induced by isoproterenol. However, the effect of FP on cardiac fibrosis after myocardial infarction (MI) as well as the underlying mechanisms is not known. In the present study, we used biochemical and histological approaches to examine the effects of FP on MI-induced cardiac fibrosis and the related mechanisms in a rat MI model and in angiotensin II- (Ang II-) treated rat cardiac fibroblasts (CFs). In vivo, MI was generated by ligation of the left anterior descending coronary artery of rats, which remained for 4 weeks. Rats were randomly divided into the sham, MI, FP (12.5 mg/kg/d), and MI+FP groups. We found that FP treatment improved heart function, reduced cardiac fibrosis, and downregulated the expression of fibrosis-related factors including collagen I, collagen III, matrix metalloproteinase-2 (MMP-2), MMP-9, transforming growth factor-β1 (TGF-β1), and p-Smad2/3, which coincided with the upregulated expression of silent information regulator 1 (SIRT1) in the hearts of MI rats. Our in vitro experiments showed that FP inhibited the proliferation and migration of primary cultured rat CFs and downregulated the expression of the above-mentioned fibrosis-related factors in Ang II-stimulated CFs. In addition, FP can decrease ROS production induced by MI and Ang II in vivo and vitro. Notably, silencing SIRT1 counteracted the FP-induced effects on CFs treated with Ang II. We conclude that FP inhibits MI-induced cardiac fibrosis through SIRT1 activation and that FP represents a potential promising drug for the treatment of MI patients in the clinic.

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Section: Discussionmentioning

confidence: 99%

Flavonoid Extract from Propolis Inhibits Cardiac Fibrosis Triggered by Myocardial Infarction through Upregulation of SIRT1

Wang

Sui

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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“…Maejima and colleagues demonstrated that telmisartan, a partial PPAR- γ agonist, could reduce TGF- β 1 expression post-MI by activating PPAR- γ in the noninfarcted myocardium in rats [ 28 ]. TGF- β 1 plays an important role in the development cardiac fibrosis [ 29 ]. The canonical TGF- β 1 and Smad2/3 signaling pathway can promote ECM production in Ang II-stimulated CFs; however, the PPAR- γ agonist curcumin could suppress ECM production by activating PPAR- γ [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…TAK1 is a mitogen-activated protein kinase kinase kinase (MAPKKK) downstream of TRAF6 [ 32 , 33 ]. Therapies that limit fibrosis have been shown to decrease TAK1 expression, consistent with its role in signaling [ 29 ]. Since Ghrelin upregulated PPAR- γ expression, we further explored the in vitro and in vivo linkage between Ghrelin and TGF- β 1 signaling.…”

Section: Discussionmentioning

confidence: 99%

Ghrelin Ameliorates Angiotensin II-Induced Myocardial Fibrosis by Upregulating Peroxisome Proliferator-Activated Receptor Gamma in Young Male Rats

Wang

Sui

Chen

et al. 2018

BioMed Research International

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Angiotensin (Ang) II contributes to the formation and development of myocardial fibrosis. Ghrelin, a gut peptide, has demonstrated beneficial effects against cardiovascular disease. In the present study, we explored the effect and related mechanism of Ghrelin on myocardial fibrosis in Ang II-infused rats. Adult Sprague-Dawley (SD) rats were divided into 6 groups: Control, Ang II (200ng/kg/min, microinfusion), Ang II+Ghrelin (100 μg/kg, subcutaneously twice daily), Ang II+Ghrelin+GW9662 (a specific PPAR-γ inhibitor, 1 mg/kg/d, orally), Ang II+GW9662, and Ghrelin for 4 wks. In vitro, adult rat cardiac fibroblasts (CFs) were pretreated with or without Ghrelin, Ghrelin+GW9662, or anti-Transforming growth factor (TGF)-β1 antibody and then stimulated with or without Ang II (100 nmol/L) for 24 h. Ang II infusion significantly increased myocardial fibrosis, expression of collagen I, collagen III, and TGF-β1, as well as TGF-β1 downstream proteins p-Smad2, p-Smad3, TRAF6, and p-TAK1 (all p<0.05). Ghrelin attenuated these effects. Similar results were seen in Ang II-stimulated rat cardiac fibroblasts in vitro. In addition, Ghrelin upregulated PPAR-γ expression in vivo and in vitro, and treatment with GW9662 counteracted the effects of Ghrelin. In conclusion, Ghrelin ameliorated Ang II-induced myocardial fibrosis by upregulating PPAR-γ and in turn inhibiting TGF-β1signaling.

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“…The AMI and ET groups were subjected to permanent ligation of the left anterior descending coronary artery (LAD), using a 6-0 suture thread to induce myocardial infarction. (9) Under deep anesthesia [ketamine (10 mg/kg body weight)], the thorax was incised at the third intercostal space, and the LAD was ligated 2 mm below the left atrium. Occlusion of the LAD was confirmed microscopically by discoloration of the ischemic area below the ligature.…”

Section: Methodsmentioning

confidence: 99%

Netrin-1 plays a role in the effect of 10 weeks moderate exercise on myocardial fibrosis in rats

Zhou

et al. 2018

Preprint

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This study aimed to determine the effect of Netrin-1 and its receptor on acute 13 myocardial infarction in rats after aerobic exercise.METHODS:Twenty-four rats were randomly 14 divided into three groups: the sham group (n = 8); acute myocardial infarction model group 15 (AMI)(n = 8); and aerobic exercise treatment after acute myocardial infarction group(ET) (n = 8). 16 After 10 weeks, the levels of netrin-1, tumor necrosis factor alpha α(TNF-α), and interleukin 6(IL-6) 17 in the serum were measured. The expression of matrix metalloproteinases 2 and 9(MMP2,9), and 18 their inhibitor, tissue inhibitor of metalloproteinases 2(TIMP2), myocardial netrin-1, Deleted in 19 colorectal cancer(DCC) receptor were evaluated. Histopathological were evaluated. The collagen 20 volume fraction of myocardial tissues was also calculated.RESULTS:Compared to the sham 21 group, the AMI group and ET groups showed increased levels of serum TNF-α, IL-6 and 22 significantly reduced levels of netrin-1. Levels of TNF-α and IL-6 were significantly reduced in 23 the ET group compared to the AMI group, whereas the level of netrin-1 was increased. The 24 expression of myocardial MMP2,9 was significantly increased in the AMI group compared to the 25 sham group, whereas that of myocardial netrin-1, inhibitor of TIMP2 and DCC receptor , was 26 significantly reduced. Compared to AMI group, the ET group showed reduced expression of 27 myocardial MMP2,9 proteins, whereas expression of myocardial netrin-1, inhibitor of TIMP2 and 28 DCC receptor, was significantly increased. The collagen volume fraction of myocardial tissues 29 was significantly increased in the AMI group and ET group compared to the sham group, with the 30 greater increase being noted in the AMI group.CONCLUSIONS: Aerobic exercise could increase 31 levels of serum netrin-1 myocardial netrin-1, and DCC receptor and reduced expression of 32 myocardial MMP2,9 proteins, to improve the degree of fibrosis following myocardial infarction 33 in rats. 34 Keywords: netrin-1, acute myocardial infarction, aerobic exercise, rats 35 51 The role of netrin-1 in cardiovascular disease and the stages of acute inflammation is an 52 emerging area of research. Some studies have shown that an appropriate increase in the 53 concentration of netrin-1, can alleviate myocardial ischemia-reperfusion injury, and reduce 54 atherosclerosis (6, 7). Liu and others (8) reported that aerobic exercise could increase the 55 expression of netrin-1 to relieve cerebral reperfusion injury in rats. However, whether aerobic 56 exercise will show similar effects in myocardial cells has not yet been reported. 57 Therefore, the present study was undertaken to discuss the netrin-1 changes after 58 myocardial fibrosis, and evaluate the effect of aerobic exercise on netrin-1 after 59 myocardial infarction. 60 61 Materials and methods 62 Animals and groups 63 Healthy adult male Sprague Dawley (SD) rats, weighing 180-220 g were supplied by the Animal 64 Experiment Center of Harbin Medical University. The rats were randoml...

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Simvastatin ameliorates ventricular remodeling via the TGF-β1 signaling pathway in rats following myocardial infarction

Cited by 27 publications

References 25 publications

Flavonoid Extract from Propolis Inhibits Cardiac Fibrosis Triggered by Myocardial Infarction through Upregulation of SIRT1

Flavonoid Extract from Propolis Inhibits Cardiac Fibrosis Triggered by Myocardial Infarction through Upregulation of SIRT1

Ghrelin Ameliorates Angiotensin II-Induced Myocardial Fibrosis by Upregulating Peroxisome Proliferator-Activated Receptor Gamma in Young Male Rats

Netrin-1 plays a role in the effect of 10 weeks moderate exercise on myocardial fibrosis in rats

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