| Objective: Acute myocardial infarction（AMI）is one of the most common critical diseases of the cardiovascular system.Because of the alteration of diet and lifestyle changes and improvement of living quality,the incidence of AMI is on the rise and has became the primary cause of morbidity and death in China.Myocardial fibrosis is the major pathological process following myocardial infarction,which may lead to cardiac remodeling and dysfunction.Over-accumulation of extracellular matrix（ECM）and increasement of cardiac fibroblasts（CFs）activity may lead to cardiac fibrosis formation,which resulting in ventricular wall sclerosis,contractile force reduction,abnormal cardiac conduction,and ultimately undesirable structural remodeling.Micro RNAs（mi RNAs）is a class of non-coding RNA of length ranging from 17 to 25 nt.Cell exosome is secreted outside the small bubbles with a diameter of 30-150 nm,which contains plenty of protein,lipids,DNA and RNA,and can be used as a novel regulator of inter-cellular communications through paracrine.The mi RNA exosomes are rooted in cardiac fibroblasts which can monitor the cross-talks between cardiac myocytes and cardiac fibroblasts,leading to cardiac hypertrophy and heart failure eventually.Although mi RNAs have been reported to be related with cardiovascular diseases,mi RNAs are in huge quantitity and have complex functions.The function and mechanism of myocardial fibrosis after myocardial infarction have not been clearly defined.Therefore,to explore the role and mechanism of mi RNA in fibrosis after MI will offer a theoretical basis for understanding the occurrence and development of the disease.Method:1.By means of in vitro,in vivo,and molecular biology experiments,we was investigated the role of mi R-195 in the process of myocardial fibrosis after myocardial infarction in rats（Part 1）.2.By means of experiments,we studied the exosome mi R-195 affects the expression of TGF-β1 and related factors in cardiomyocytes and fibroblasts（Part 2）.3.By means of experiments,we studied the regulation of mi R-195 on TGF-β1/Smad signaling pathway during myocardial fibrosis after myocardial infarction in rats（Part 3）.Results: 1.Animal experiments showed that mi R-195 was highly expressed in the heart tissues of AMI rats.The relative expression levels of TGF-β1 and Smad3 were significantly increased,while the relative expression levels of Smad7 were significantly decreased.The level of type I collagen was reduced and myocardial fiber tissue damage is reduced after mi R-195 intervention.2.The in vivo experiments found that mi R-195 could induce fibroblast activation and promote fibrogenesis by regulating the expression of secretory factors（TNFα,TGFβ,IL-6,IL-1α,IL-1β,MCP1,VEGF,and IL-15）in cardiomyocytes.3.The in vivo experiments found that angiotensin II promoted the activation of fibroblasts stimulated by mi R-195.Mi R-195 can mediate TGF-β1 in the form of exosomes by enhancing the transcriptional activity of AP-1 and RAS signals in the form of positive feedback to activate the autopromoter,thus achieving the role of promoting fibrosis.Conclusions: 1.mi R-195 is highly expressed in heart tissues of AMI rats.The level of type I collagen was reduced and myocardial fiber tissue damage is reduced after mi R-195 intervention.2.mi R-195 can activate the occurrence of post-myocardial infarction fibrosis through the TGF-β1/Smad signaling pathway,and the increased expression of TGF-β1 activates its own promoter by enhancing the transcriptional activity of AP-1 and RAS signals in the form of positive feedback. |
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