Alprostadil alleviates myocardial fibrosis in rats with diabetes mellitus through TGF-β1/Smad signaling pathway

Li, Rongji; Qi, Changliang; Feng, Qian; Ding, Peng; Kang, Le; Chi, Jinfeng

doi:10.23736/s0391-1977.19.03114-6

Cited by 3 publications

(2 citation statements)

References 5 publications

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“…The pathological features of myocardial fibrosis involve excess deposition of extracellular matrix (ECM) [ 5 ], resulting in the thickening and stiffness of the cardiac walls increased, leads to heart failure, cardiac dysfunction, arrhythmias, and heart attacks, and eventually cardiovascular death. [ 6 , 7 ]. Cardiac fibroblasts (CFs) are one of the main effectors in fibrotic scar formation in the heart, owing to their role in ECM turnover [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7

Luo,

Fu,

Wang

et al. 2023

Chin Med

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Background Salvianolic acid B (Sal B), a water-soluble phenolic compound derived from Salvia miltiorrhiza Bunge, is commonly used in Traditional Chinese Medicine to treat cardiovascular disease. In our previous study, Sal B protected against myocardial fibrosis induced by diabetic cardiomyopathy (DCM). This study aimed to investigate the ameliorative effects and potential mechanisms of Sal B in mitigating myocardial fibrosis induced by DCM. Methods Various methods were used to investigate the effects of Sal B on myocardial fibrosis induced by DCM in vivo and in vitro. These methods included blood glucose measurement, echocardiography, HE staining, Masson’s trichrome staining, Sirius red staining, cell proliferation assessment, determination of hydroxyproline levels, immunohistochemical staining, evaluation of fibrosis-related protein expression (Collagen-I, Collagen-III, TGF-β1, p-Smad3, Smad3, Smad7, and α-smooth muscle actin), analysis of Smad7 gene expression, and analysis of Smad7 ubiquitin modification. Results The animal test results indicated that Sal B significantly improved cardiac function, inhibited collagen deposition and phenotypic transformation, and ameliorated myocardial fibrosis in DCM by upregulating Smad7, thereby inhibiting the TGF-β1 signaling pathway. In addition, cell experiments demonstrated that Sal B significantly inhibited the proliferation, migration, phenotypic transformation, and collagen secretion of cardiac fibroblasts (CFs) induced by high glucose (HG). Sal B significantly decreased the ubiquitination of Smad7 and stabilized the protein expression of Smad7, thereby increasing the protein expression of Smad7 in CFs and inhibiting the TGF-β1 signaling pathway, which may be the potential mechanism by which Sal B mitigates myocardial fibrosis induced by DCM. Conclusion This study revealed that Sal B can improve myocardial fibrosis in DCM by deubiquitinating Smad7, stabilizing the protein expression of Smad7, and blocking the TGF-β1 signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7

Luo,

Fu,

Wang

et al. 2023

Chin Med

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show abstract

“…Diabetic cardiomyopathy (DCM) which caused by DM, is one of the most common reason of morbidity and mortality in patients globally, contributing to over 50 % diabetic death [2], while myocardial fibrosis is the main pathological features of DCM [3,4]. The pathological features of myocardial fibrosis involves an excess deposition of extracellular matrix (ECM) [5], which can cause cardiac dysfunction, arrhythmias, and heart attacks [6,7]. Cardiac fibroblasts (CFs) are known as one of the main effectors in fibrotic scar formation in the heart due to their role in ECM turnover [8].…”

Section: Introductionmentioning

confidence: 99%

Salvianolic Acid B (Sal B) ameliorates myocardial fibrosis in diabetic cardiomyopathy through deubiquitinating Smad7

Luo,

Fu,

Wang

et al. 2023

Preprint

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Background Salvianolic acid B (Sal B), a water-soluble phenolic compound derived from Salvia Miltiorrhiza Bunge, is commonly used in Chinese Traditional Medicine for the treatment of cardiovascular diseases. Sal B has shown protecting effects against myocardial fibrosis induced by diabetic cardiomyopathy(DCM) in our previous experiment. This study aimed to investigate the ameliorative effects and potential mechanisms of Sal B in mitigating myocardial fibrosis induced by DCM. Methods In this study, a variety of methods were utilized to investigate the effects of Sal B on improving myocardial fibrosis induced by DCM in vivo and in vitro. These methods included weight measurement, blood glucose analysis, echocardiography, HE staining, Masson's trichrome staining, Sirius red staining, cell proliferation assessment, determination of hydroxyproline levels, immunohistochemical staining, evaluation of fibrosis-associated protein expression (Collagen I, Collagen III, TGF-β1, p-Smad3, Smad3, Smad7, and α-smooth muscle actin), analysis of Smad7 gene expression, and analysis of Smad7 ubiquitin modification. Results The animal test results indicated Sal B could significantly improve cardiac function, inhibit collagen deposition and phenotypic transformation, ameliorate myocardial fibrosis in DCM by up-regulating Smad7, thereby inhibiting TGF-β1 signaling pathway. Additionally, cell experiments demonstrated Sal B could significantly inhibit the proliferation, migration, phenotypic transformation and collagen secretion of cardiac fibroblasts (CFs) induced by high glucose(HG). Sal B could significantly decrease the ubiquitization modifications of Smad7, stabilize the protein expression of Smad7, therefore increase the protein expression of Smad7 in the CFs , inhibit TGF-β1 signaling pathway, that maybe a potential mechanism of Sal B in mitigating myocardial fibrosis induced by DCM. Conclusion In summary, this study revealed that Salvianolic acid B can improve myocardial fibrosis in DCM by deubiquitinating Smad7, stabilizing the protein expression of Smad7, blocking the TGF-β1 signaling pathway.

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Potential clinical biomarkers and perspectives in diabetic cardiomyopathy

Deng

Fang

Tian

et al. 2023

Diabetol Metab Syndr

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Diabetic cardiomyopathy (DCM) is a serious cardiovascular complication and the leading cause of death in diabetic patients. Patients typically do not experience any symptoms and have normal systolic and diastolic cardiac functions in the early stages of DCM. Because the majority of cardiac tissue has already been destroyed by the time DCM is detected, research must be conducted on biomarkers for early DCM, early diagnosis of DCM patients, and early symptomatic management to minimize mortality rates among DCM patients. Most of the existing implemented clinical markers are not very specific for DCM, especially in the early stages of DCM. Recent studies have shown that a number of new novel markers, such as galactin-3 (Gal-3), adiponectin (APN), and irisin, have significant changes in the clinical course of the various stages of DCM, suggesting that we may have a positive effect on the identification of DCM. As a summary of the current state of knowledge regarding DCM biomarkers, this review aims to inspire new ideas for identifying clinical markers and related pathophysiologic mechanisms that could be used in the early diagnosis and treatment of DCM.

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Alprostadil alleviates myocardial fibrosis in rats with diabetes mellitus through TGF-β1/Smad signaling pathway

Cited by 3 publications

References 5 publications

Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7

Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7

Salvianolic Acid B (Sal B) ameliorates myocardial fibrosis in diabetic cardiomyopathy through deubiquitinating Smad7

Potential clinical biomarkers and perspectives in diabetic cardiomyopathy

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