Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renin-angiotensin-aldosterone system has emerged as a potential candidate for the accumulation of collagen in cardiac fibroblasts. The traditional renin-angiotensin-aldosterone system can be considered a system in which circulating angiotensin II or aldosterone is delivered to target tissue or cells. However, an independent local renin-angiotensin system has also been described in cardiac cells and evidence has been accumulated for autocrine and/or paracrine pathways by which biological actions of angiotensin II can be mediated. These actions of angiotensin II are primarily mediated through angiotensin II receptors of the subtype I (AT1). When evaluating the effects of angiotensin II in situ, changes in circulating levels and local production both have to be taken into account. Functional angiotensin II receptors have been documented in cardiac fibroblasts although the presence of aldosterone receptors in cardiac fibroblasts is obscure, and the expression of mRNA for mineralocorticoid receptors in cardiac fibroblasts has been described. In vitro, angiotensin II increased cardiac fibroblast-mediated collagen synthesis and mRNA levels of collagen type I, type III, pro-alpha 1 (I) collagen, pro-alpha 1 (III) collagen and fibronectin, and inhibited matrix metalloproteinase I activity. The ability of angiotensin II to induce collagen synthesis and expression of collagen in cardiac fibroblasts may be mediated by an increase in transforming growth factor-beta 1 in an autocrine/paracrine fashion. The angiotensin II-stimulated secretion and expression of collagen was completely abolished by AT1 receptor antagonism, but not affected by AT2 receptor antagonism. The discordant findings that have been reported concerning the in vitro effect of aldosterone on collagen synthesis in cardiac fibroblasts can at least partly be attributed to differences in methodology such as the use of the total population or a sub-population of cardiac fibroblasts. In vivo, chronic infusion of angiotensin II or aldosterone increased the collagen volume fraction in the ventricles. Angiotensin-converting enzyme (ACE) inhibition and AT1 receptor antagonism, but not AT2 receptor antagonism, reduced collagen deposition in the myocardium in spontaneously hypertensive rats. The cardioprotective mechanism of action of ACE inhibitors can be attributed to local blockade of the formation of angiotensin II, to the degradation of bradykinin or to the release of nitric oxide and/or eicosanoids. Angiotensin-converting enzyme inhibitors also reduced collagen deposition in rat myocardium following myocardial infarction suggesting that collagen deposition may in part result from mechanisms other than through AT1 receptors. However, further research is necessary to unravel the various mechanisms involved in the action of angiotensin-converting enzyme inhibitors or of AT1 receptor antagonists on collagen deposition in the myocardium.
 ...
PMID:Antagonism of the renin-angiotensin-aldosterone system and collagen metabolism in cardiac fibroblasts. 1038 25

Renin-angiotensin system (RAS) is activated in diabetes. The rise of angiotension II (Ang II) stimulates the cardiac fibroblast proliferation and the alteration of collagen metabolism through AT1 receptor on cell surface, causing the myocardium interstitial and perivascular fibrosis, and the ventricular myocardium rigidity and diastolic function disturbance, leading to the clinical symptoms of diabetic cardiomyopathy (DCM). The main members of RAS including Ang II, Ang-(1-7), Ac-SDKP and ATR play the important role in the development of DCM. This article reviewed the interactions between RAS and endothelin (ET), reactive oxygen species (ROS), transforming growth factor-beta 1 (TGF-beta 1), nuclear factor-kappa b (NF-kappaB), signal transduction system and apoptosis in DCM.
 ...
PMID:[Research progress in relations between renin angiotensin system and diabetic cardiomyopathy]. 2206 18


<< Previous 1 2