IL-17 induces myocardial fibrosis and enhances RANKL/OPG and MMP/TIMP signaling in isoproterenol-induced heart failure
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Myocardial fibrosis
Myocardial Fibrosis,caused by the imbalance of collagen metabolism,is crucial for the transformation from viral myocarditis to dilated cardiomyopathy.Recently,it is demonstrated that matrix metalloproteinases and their tissue inhibitors(MMPs/TIMP),as a collagen degeneration system,are related to the imbalance of collagen metabolism to the formation of myocardial fibrosis.
Myocardial fibrosis
Viral Myocarditis
Dilated Cardiomyopathy
Degeneration (medical)
Endomyocardial fibrosis
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ABSTRACT Fibrosis – a debilitating condition that can occur in most organs – is characterized by excess deposition of a collagen-rich extracellular matrix (ECM). At first sight, the activities of proteinases that can degrade matrix, such as matrix metalloproteinases (MMPs), might be expected to be under-expressed in fibrosis or, if present, could function to resolve the excess matrix. However, as we review here, some MMPs are indeed anti-fibrotic, whereas others can have pro-fibrotic functions. MMPs modulate a range of biological processes, especially processes related to immunity and tissue repair and/or remodeling. Although we do not yet know precisely how MMPs function during fibrosis – that is, the protein substrate or substrates that an individual MMP acts on to effect a specific process – experiments in mouse models demonstrate that MMP-dependent functions during fibrosis are not limited to effects on ECM turnover. Rather, data from diverse models indicate that these proteinases influence cellular activities as varied as proliferation and survival, gene expression, and multiple aspects of inflammation that, in turn, impact outcomes related to fibrosis.
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The purpose of this study was to assess the effects of 12 weeks of atorvastatin treatment on myocardial fibrosis in patients with hypertension with atherosclerosis. 15 statin-naïve participants (11 males; mean age 67±10 years) with atherosclerosis were given atorvastatin (40 mg/day) for 12 weeks and underwent echocardiography including ultrasonic tissue characterization by cyclic variation of integrated backscatter (CVIBS). Serum galectin-3 and fibrosis markers including aminoterminal propeptide of type III procollagen (PIIINP), matrix metalloproteinase-2, metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) were also analyzed. After 12 weeks of atorvastatin (40 mg/day) treatment, serum total cholesterol and low-density lipoprotein cholesterol decreased significantly (204±31 to 140±24 mg/dL and 133±26 to 69±17 ng/mL, respectively, both p<0.001). In myocardial fibrosis analysis, CVIBS increased significantly (6.6±1.9 to 8.5±2.7 dB, p=0.024). In addition, the circulating fibrosis markers serum PIIINP and TIMP-1 decreased significantly (9.5±2.7 to 6.4±1.4 ng/mL, p=0.012 and 299±65 to 250±45 ng/mL, p=0.024, respectively). 12 weeks of medium dose atorvastatin treatment resulted in a significant reduction in myocardial fibrosis as evaluated by morphofunctional parameters and plasma markers of tissue fibrosis.NTC00172419; results.
Myocardial fibrosis
Procollagen peptidase
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Myocardial fibrosis is characterized by excessive deposition of myocardial interstitial collagen, abnormal distribution, and excessive proliferation of fibroblasts. According to the researches in recent years, myocardial fibrosis, as the pathological basis of various cardiovascular diseases, has been proven to be a core determinant in ventricular remodeling. Pressure load is one of the causes of myocardial fibrosis. In experimental models of pressure-overload-induced myocardial fibrosis, significant increase in left ventricular parameters such as interventricular septal thickness and left ventricular posterior wall thickness and the decrease of ejection fraction are some of the manifestations of cardiac damage. These morphological and functional changes have a serious impact on the maintenance of physiological functions. Therefore, establishing a suitable myocardial fibrosis model is the basis of its pathogenesis research. This paper will discuss the methods of establishing myocardial fibrosis model and compare the advantages and disadvantages of the models in order to provide a strong basis for establishing a myocardial fibrosis model.
Myocardial fibrosis
Pressure overload
Pathogenesis
Interventricular septum
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The hearts of 28 necropsy cases with DCM and 10 control cases were analysed to elucidate the role of myocarditis and fibrosis in dilated cardiomyopathy (DCM). The extent of fibrosis and myocyte diameter were measured in the transverse sections of the left ventricle. The degree and pattern of fibrosis varied widely from case to case. The DCM cases were then classified into 3 groups: 1) Group la, 8 cases with mild diffuse fibrosis; 2) Group Ib, 9 cases with severe diffuse fibrosis and 3) Group II, 11 cases with segmental fibrosis.Myocardial fibrosis and hypertrophy were significantly more prominent in Groups Ib and II than in the control group (p<0.01), but no differences were observed between Group la and the control group. Thus, it is reasonable to attribute the chronic CHF and LV dilatation in Groups Ib and II to the extensive myocardial fibrosis. In contrast, it is not reasonable to attribute the chronic CHF and LV dilatation in Group la to myocardial fibrosis.Focal lymphoid cell infiltration was graded to assess inflammatory changes. Group II showed more prominent inflammatory changes than the other 2 groups (p<0.05). Thus, it is possible that myocarditis is an etiologic factor for DCM with a segmental pattern of fibrosis.
Myocardial fibrosis
Dilated Cardiomyopathy
Endomyocardial fibrosis
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Myocardial fibrosis is the hallmark of myocardial remodelling found in hypertensive individuals. This process adversely affects the outcomes of such patients and results in diastolic and systolic cardiac dysfunction, electrical dysrhythmia and potentially sudden death. Collagen metabolism has been highlighted as the primary mechanism by which fibrosis is regulated. However, there are many other facets to the pathophysiology of myocardial fibrosis including mechanical, cellular and hormonal influences, which may guide therapy and thereby determine prognosis.
Myocardial fibrosis
Pathophysiology
Cardiac Fibrosis
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Abstract Myocardial fibrosis is observed in many cardiovascular diseases including hypertension, heart failure and cardiomyopathy. Myocardial fibrosis has been proved to be reversible and treatable only under timely intervention, which makes early detection and assessment of fibrosis crucial. Aside from tissue biopsy as the gold standard for the diagnosis of myocardial fibrosis, circulating biomarkers have been adopted as noninvasive assessment of this lesion. Dysregulated collagen deposition is thought to be the major cause of myocardial fibrosis. Collagens, procollagens, TGF-β, TIMP, galectin-3, and microRNAs are thought to be indicators of myocardial fibrosis. In this review, we summarize the molecules that are frequently used as biomarkers in diagnosis of cardiac fibrosis. Mechanisms of fibrosis that they take part in are also introduced.
Myocardial fibrosis
Cardiac Fibrosis
Gold standard (test)
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Although hypertensive heart disease (HHD) is clinically characterized by development of left ventricular hypertrophy in the absence of a cause other than arterial hypertension, changes in the composition of myocardial tissue also develop in arterial hypertension, leading to structural remodeling of the myocardium (eg, fibrosis). Myocardial fibrosis is the major determinant of diastolic dysfunction/failure in patients with HHD. Recent available data on the determination of serum concentrations of collagen-derived serum peptides, as well as quantitative analysis of echoreflectivity to address the presence of fibrosis in the myocardium of hypertensive patients, are promising. In addition, preliminary data suggest that the goal of reducing myocardial fibrosis is achievable using specific pharmacological agents in patients with HHD. (Circ J 2008; Suppl A: A-8 - A-12)
Hypertensive heart disease
Myocardial fibrosis
Myocardial hypertrophy
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Cardiac fibrosis stiffens the ventricular wall, predisposes to cardiac arrhythmias and contributes to the development of heart failure. In the present study, our aim was to identify novel miRNAs that regulate the development of cardiac fibrosis and could serve as potential therapeutic targets for myocardial fibrosis.Analysis for cardiac samples from sudden cardiac death victims with extensive myocardial fibrosis as the primary cause of death identified dysregulation of miR-185-5p. Analysis of resident cardiac cells from mice subjected to experimental cardiac fibrosis model showed induction of miR-185-5p expression specifically in cardiac fibroblasts. In vitro, augmenting miR-185-5p induced collagen production and profibrotic activation in cardiac fibroblasts, whereas inhibition of miR-185-5p attenuated collagen production. In vivo, targeting miR-185-5p in mice abolished pressure overload induced cardiac interstitial fibrosis. Mechanistically, miR-185-5p targets apelin receptor and inhibits the anti-fibrotic effects of apelin. Finally, analysis of left ventricular tissue from patients with severe cardiomyopathy showed an increase in miR-185-5p expression together with pro-fibrotic TGF-β1 and collagen I.Our data show that miR-185-5p targets apelin receptor and promotes myocardial fibrosis.
Cardiac Fibrosis
Myocardial fibrosis
Apelin
Pressure overload
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Changes in the composition of cardiac tissue develop in hypertensive patients with left ventricular hypertrophy (ie, hypertensive heart disease) and lead to structural remodeling of the myocardium. One of these changes is related to the disruption of the equilibrium between the synthesis and degradation of collagen types I and III molecules, which results in an excessive accumulation of collagen types I and III fibers within the myocardium. Myocardial fibrosis is the consequence of a number of pathologic processes mediated by mechanical, neurohormonal, and cytokine routes. The clinical relevance of fibrosis is that it may contribute to heart failure and other cardiac complications in patients with hypertensive heart disease. This brief review focuses on the mechanisms of hypertensive myocardial fibrosis.
Hypertensive heart disease
Myocardial fibrosis
Cardiac Fibrosis
Clinical Significance
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