Effects of intermedin1-53 on myocardial fibrosis

Yang, Xia; Zhang, Huiping; Jia, Yanjie; Ni, Lan; Li, Guizhong; Xue, Ling; Jiang, Yideng

doi:10.1093/abbs/gms093

Cited by 12 publications

(7 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Domestic and international studies have reported that during the formation of scar tissue, TGF-β is believed to promote scar generation [1,8]. It also has the physiological function of promoting fibroblast growth and the expression of extracellular matrix (ECM), and inhibits the degradation of ECM.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Intermedin 1-53 Inhibits Myocardial Fibrosis in Rats by Down-Regulating Transforming Growth Factor-β

et al. 2017

View full text Add to dashboard Cite

BackgroundMyocardial fibrosis is the result of persistent anoxia and ischemic myocardial fibers caused by coronary atherosclerotic stenosis, which lead to heart failure, threatening the patient’s life. This study aimed to explore the regulatory role of intermedin 1-53 (IMD1-53) in cardiac fibrosis using neonatal rat cardiac fibroblasts and a myocardial infarction (MI) rat model both in vitro and in vivo.Material/MethodsThe Western blot method was used to detect the protein expression of collagen I and collagen III in myocardial fibroblasts. The SYBR Green I real-time quantitative polymerase chain reaction (PCR) assay was used to detect the mRNA expression of collagen type I and III, IMD1-53 calcitonin receptor-like receptor (CRLR), transforming growth factor-β (TGF-β), and matrix metalloproteinase-2 (MMP-2). Masson staining was used to detect the area changes of myocardial fibrosis in MI rats.ResultsResults in vivo showed that IMD1-53 reduced the scar area on the heart of MI rats and inhibited the expression of collagen type I and III both in mRNA and protein. Results of an in vitro study showed that IMD1-53 inhibited the transformation of cardiomyocytes into myofibroblasts caused by angiotensin II (Ang II). The further mechanism study showed that IMD1-53 inhibited the expression of TGF-β and the phosphorylation of smad3, which further up-regulated the expression of MMP-2.ConclusionsIMD1-53 is an effective anti-fibrosis hormone that inhibits cardiac fibrosis formation after MI by down-regulating the expression of TGF-β and the phosphorylation of smad3, blocking fibrous signal pathways, and up-regulating the expression of MMP-2, thereby demonstrating its role in regression of myocardial fibrosis.

show abstract

Section: Discussionmentioning

confidence: 99%

“…ECM is a dynamic network structure composed of macromolecules such as collagen, proteoglycans, and glycoproteins [8], whose synthesis and degradation are influenced by many factors. The basic characteristics of tissue fibrosis showed the alterations of organizational structure and excessive deposition of ECM [23].…”

Section: Discussionmentioning

confidence: 99%

Intermedin 1-53 Inhibits Myocardial Fibrosis in Rats by Down-Regulating Transforming Growth Factor-β

et al. 2017

View full text Add to dashboard Cite

show abstract

“…However, it is necessary to further address whether ZAC promotedcardiac repair is associated with modulation of protein kinases. Synthesis and deposition of collagens are known to induce the fibrosis predisposing the heart to undergo maladaptive tissue repair and heart failure [28]. Activated cardiac fibroblasts synthesize and release collagens among many other extracellular matrix-related proteins.…”

Section: +mentioning

confidence: 99%

Opening of the inward rectifier potassium channel alleviates maladaptive tissue repair following myocardial infarction

Liu¹,

Liu²,

Luo³

et al. 2016

ABBS

View full text Add to dashboard Cite

Activation of the inward rectifier potassium current (IK1) channel has been reported to be associated with suppression of ventricular arrhythmias. In this study, we tested the hypothesis that opening of the IK1 channel with zacopride (ZAC) was involved in the modulation of tissue repair after myocardial infarction. Sprague-Dawley rats were subject to coronary artery ligation and ZAC was administered intraperitoneally (15 µg/kg/day) for 28 days. Compared with the ischemia group, treatment with ZAC significantly reduced the ratio of heart/body weight and the cross-sectional area of cardiomyocytes, suggesting less cardiac hypertrophy. ZAC reduced the accumulation of collagen types I and III, accompanied with decrease of collagen area, which were associated with a reduction of collagen deposition in the fibrotic myocardium. Echocardiography showed improved cardiac function, evidenced by the reduced left ventricular end-diastolic dimension and left ventricular end-systolic dimension, and the increased ejection fraction and fractional shortening in ZAC-treated animals (all P < 0.05 vs. ischemia group). In coincidence with these changes, ZAC upregulated the protein level of the IK1 channel and down-regulated the phosphorylation of mammalian target of rapamycin (mTOR) and 70-kDa ribosomal protein S6 (p70S6) kinase. Administration of chloroquine alone, an IK1 channel antagonist, had no effect on all the parameters measured, but significantly blocked the beneficial effects of ZAC on cardiac repair. In conclusion, opening of the IK1 channel with ZAC inhibits maladaptive tissue repair and improves cardiac function, potentially mediated by the inhibition of ischemia-activated mTOR-p70S6 signaling pathway via the IK1 channel. So the development of pharmacological agents specifically targeting the activation of the IK1 channel may protect the heart against myocardial ischemia-induced cardiac dysfunction.

show abstract

“…The human IMD gene encodes a prepropeptide of 148 amino acids (preproIMD); proteolytic cleavage of preproIMD yields a series of biologically active C-terminal fragments. Previous studies have revealed that an endogenous degraded fragment termed IMD 1–53 , which contains cleavage sites located between two basic amino acids at Arg93-Arg94, possessed potent cardioprotective activities in multiple physiopathological processes, including ischemia/reperfusion injury (5,6), cardiac fibrosis (7) and cardiac hypertrophy (8,9). However, the mechanisms underlying the cardioprotective effects of IMD require further elucidation.…”

Section: Introductionmentioning

confidence: 99%

Intermedin1–53 enhances angiogenesis and attenuates adverse remodeling following myocardial infarction by activating AMP-activated protein kinase

Chen

Yan

et al. 2017

Molecular Medicine Reports

View full text Add to dashboard Cite

Adverse ventricular remodeling is a maladaptive response to acute loss of myocardium and an important risk factor for heart failure following myocardial infarction (MI). Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide family, which may possess potent cardioprotective properties. The aim of the present study was to determine whether IMD1–53, a mature bioactive form of IMD, may promote therapeutic angiogenesis within the infarcted myocardium, therefore attenuating adverse ventricular remodeling post-MI. The present study observed that treatment with IMD1–53 promoted proliferation, migration and tube formation of primary cultured myocardial microvascular endothelial cells (MMVECs). In a rat model of MI, chronic administration of IMD1–53 increased capillary density in the peri-infarct zone, attenuated ventricular remodeling and improved cardiac performance post-MI. Treatment with IMD1–53 also significantly increased the expression levels of phosphorylated-AMP-activated protein kinase (AMPK) and the subsequent activation of endothelial nitric oxide synthase in MMVECs and post-MI rat myocardium, without a significant influence on the expression of vascular endothelial growth factor. Notably, the in vitro effects of IMD1–53 on angiogenesis and the in vivo effects of IMD1–53 on post-MI ventricular remodeling were largely abrogated by the co-administration of compound C, an AMPK inhibitor. In conclusion, the present study demonstrated that IMD1–53 could attenuate adverse ventricular remodeling post-MI via the promotion of therapeutic angiogenesis, possibly through the activation of AMPK signaling.

show abstract

Effects of intermedin1-53 on myocardial fibrosis

Cited by 12 publications

References 26 publications

Intermedin 1-53 Inhibits Myocardial Fibrosis in Rats by Down-Regulating Transforming Growth Factor-β

Intermedin 1-53 Inhibits Myocardial Fibrosis in Rats by Down-Regulating Transforming Growth Factor-β

Opening of the inward rectifier potassium channel alleviates maladaptive tissue repair following myocardial infarction

Intermedin1–53 enhances angiogenesis and attenuates adverse remodeling following myocardial infarction by activating AMP-activated protein kinase

Contact Info

Product

Resources

About