Ramipril attenuates left ventricular remodeling by regulating the expression of activin A-follistatin in a rat model of heart failure

Wang, Qun; Liu, Haiyan; Liu, Miao; Yang, Chunyan; Yang, Jie; Liu, Zhonghui; Yang, Ping

doi:10.1038/srep33677

Cited by 13 publications

(8 citation statements)

References 48 publications

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“…The improved skin parameters were associated with the downregulated phosphorylation of SMAD2/3 and TAK1, which indicated the inhibition of both the canonical and noncanonical TGF-β1 pathways. Our results are consistent with previous reports on the effects of the RAS on myocardial infarction, which demonstrate the efficacy of ramipril in reducing fibrosis and collagen accumulation 31 , 32 . Our results also suggest that the beneficial effects of the RAS blockade induced by ACEI probably also extend to ARBs, such as losartan.…”

Section: Discussionsupporting

confidence: 93%

Angiotensin-converting enzyme inhibitor reduces scar formation by inhibiting both canonical and noncanonical TGF-β1 pathways

Fang

Wang

Zhao

et al. 2018

Sci Rep

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Angiotensin-converting enzyme inhibitors (ACEIs) can improve the fibrotic processes in many internal organs. Recent studies have shown a relationship between ACEI with cutaneous scar formation, although it has not been confirmed, and the underlying mechanism is unclear. In this study, we cultured mouse NIH 3T3 fibroblasts with different concentrations of ACEI. We measured cell proliferation with a Cell Counting Kit-8 and collagen expression with a Sirius Red Collagen Detection Kit. Flow cytometry and western blotting were used to detect transforming growth factor β1 (TGF-β1) signaling. We also confirmed the potential antifibrotic activity of ACEI in a rat scar model. ACEI reduced fibroblast proliferation, suppressed collagen and TGF-β1 expression, and downregulated the phosphorylation of SMAD2/3 and TAK1, both in vitro and in vivo. A microscopic examination showed that rat scars treated with ramipril or losartan were not only narrower than in the controls, but also displayed enhanced re-epithelialization and neovascularization, and the formation of organized granulation tissue. These data indicate that ACEI inhibits scar formation by suppressing both TGF-β1/SMAD2/3 and TGF-β1/TAK1 pathways, and may have clinical utility in the future.

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Section: Discussionsupporting

confidence: 93%

Angiotensin-converting enzyme inhibitor reduces scar formation by inhibiting both canonical and noncanonical TGF-β1 pathways

Fang

Wang

Zhao

et al. 2018

Sci Rep

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“…12,31 Specifically, it has been shown that overexpression of activin A leads to ventricular remodelling in rat models of heart failure. 33 Besides these effects, activin A has been described as an additional factor contributing to diabetic cardiomyopathy. 32 Recent research has also demonstrated that the secretome from human epicardial (but not subcutaneous) adipose tissue can induce myocardial fibrosis and that the adipo-fibrokine activin A constitutes an important mediator of this profibrotic effect, which can be neutralized by an anti-activin A antibody.…”

Section: Discussionmentioning

confidence: 99%

“…7 Interestingly, further findings have suggested that the angiotensin-converting enzyme inhibitor Ramipril benefited LV remodelling by reducing fibrosis and collagen accumulation in the left ventricle of rats after myocardial infarction, an observation which was also associated with down-regulation of activin A expression. 33 Besides these effects, activin A has been described as an additional factor contributing to diabetic cardiomyopathy. 14,23 Activin A released from epicardial adipose tissue of obese type 2 diabetic patients provoked impairment of myocardial contractility by reduction of sarcomer shortening, cytosolic calcium flow and expression of sarco/endoplasmic reticulum Ca 2+ ATPase and decreased insulin-mediated glucose uptake in atrial rat cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

The adipo‐fibrokine activin A is associated with metabolic abnormalities and left ventricular diastolic dysfunction in obese patients

et al. 2019

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Aims Left ventricular diastolic dysfunction (LVDD) is common in obese subjects, and a relationship between epicardial adipose tissue (EAT), increased adipocytokines, and cardiovascular diseases has been reported. This study sought to examine as to whether the adipo‐fibrokine activin A is a link between increased EAT, the metabolic syndrome (MetS), and LVDD in severely obese subjects. Methods and results In 236 obese subjects (ø body mass index 39.8 ± 7.9 kg/m 2 ) with a variable degree of the MetS and in 60 healthy non‐obese controls (ø body mass index 24.8 ± 3.4 kg/m 2 ), serum activin A levels were measured and correlated with parameters of the MetS, epicardial fat thickness (EFT), and echocardiographic parameters of LVDD. Activin A levels were higher in obese than in non‐obese subjects (362 ± 124 vs. 301 ± 94 pg/mL, P = 0.0004), increased with the number of MetS components (from 285 ± 82 with no MetS component, 323 ± 94 with one or two MetS components, to 403 ± 131 pg/mL with ≥3 MetS components, P < 0.0001) and correlated with EFT ( r = 0.41, P < 0.001). Furthermore, activin A levels were related to several parameters of LVDD [e.g. left atrial size (382 ± 117 vs. 352 125 pg/mL, P = 0.024), E/e′ (394 ± 108 vs. 356 ± 127 pg/mL, P = 0.005)]. LVDD was highest in MetS obese subjects with high EFT (44.3%) compared with MetS obese subjects with low EFT (27.0%), non‐MetS obese subjects with high EFT (24.2%), and non‐MetS obese subjects with low EFT (10.6%, P < 0.0001). Conclusions In severe obesity, activin A was significantly related to EFT, MetS, and LVDD, implicating MetS‐related alterations in the secretory profile of EAT in the pathogenesis of obesity‐related heart disease.

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“…As the cornerstone of clinical treatment of heart failure, angiotensin-converting enzyme inhibitors (ACEIs) improve ventricular remodeling (Wei et al, 2016). However, whether ACEIs improve ventricular remodeling in rabbits with ischemic heart failure in association with Gal-3 downregulation remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Perindopril and a Galectin-3 Inhibitor Improve Ischemic Heart Failure in Rabbits by Reducing Gal-3 Expression and Myocardial Fibrosis

Hao

et al. 2019

Front. Physiol.

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Objective: Ventricular remodeling is considered the basis of heart failure and is involved in myocardial fibrosis. This study aimed to assess perindopril and a galectin-3 inhibitor (modified citrus pectin, MCP) for their effects on ventricular remodeling and myocardial fibrosis in rabbits with ischemic heart failure. Methods: Rabbits were divided into sham, heart failure (model), MCP, and perindopril groups, respectively. A rabbit model of ischemic heart failure was established by ligating the anterior descending coronary artery. Then, the rabbits were orally administered MCP, perindopril, or saline (all at 2 ml/kg/d) for 4 weeks. Sham animals only underwent open heart surgery without further treatment. After 4 weeks, cardiac function was examined by ultrasound, and myocardial Gal-3, collagen type I, and collagen type III expression was assessed, at the gene and protein levels, by real-time PCR and Western-Blot, respectively; serum Gal-3 was detected by ELISA, and fibrosis in the infarct zone was evaluated by H&E and Masson staining. Results: In model animals, myocardial Gal-3, collagen type I, and collagen type III gene and protein expression levels were increased compared with control values, as well as serum Gal-3 amounts. Treatment with perindopril and MCP significantly alleviated the above effects, with no significant differences between the treatment groups. Pathological analyses showed that compared with model animals, treatment with MCP or perindopril resulted in relatively neatly arranged myocardial cells in the infarct zone, with significantly decreased fibrosis. Conclusion: Perindopril and the galectin-3 inhibitor MCP comparably improve ischemic heart failure in rabbits, by downregulating Gal-3 and reducing myocardial fibrosis.

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Ramipril attenuates left ventricular remodeling by regulating the expression of activin A-follistatin in a rat model of heart failure

Cited by 13 publications

References 48 publications

Angiotensin-converting enzyme inhibitor reduces scar formation by inhibiting both canonical and noncanonical TGF-β1 pathways

Angiotensin-converting enzyme inhibitor reduces scar formation by inhibiting both canonical and noncanonical TGF-β1 pathways

The adipo‐fibrokine activin A is associated with metabolic abnormalities and left ventricular diastolic dysfunction in obese patients

Perindopril and a Galectin-3 Inhibitor Improve Ischemic Heart Failure in Rabbits by Reducing Gal-3 Expression and Myocardial Fibrosis

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