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Myocardial fibrosis and the renin-angiotensin-aldosterone system
1Division of Cardiology, University of Missouri-Columbia 65212.
Insights
Left ventricular hypertrophy (LVH) involves nonmyocyte cells, not just heart muscle growth, leading to myocardial failure. Hormonal systems like renin-angiotensin-aldosterone drive fibrosis, a key factor in heart dysfunction.
Area of Science:
- Cardiology
- Pathophysiology
- Molecular Biology
Background:
- Left ventricular hypertrophy (LVH) is a primary risk factor for myocardial failure.
- Pathologic LVH involves abnormal remodeling driven by nonmyocyte cells, not solely myocyte growth.
- Chronic hormonal elevations alter nonmyocyte behavior, contributing to fibrosis via fibroblast proliferation and collagen synthesis.
Purpose of the Study:
- To review experimental findings on myocardial fibrosis in arterial hypertension.
- To examine the role of circulating and locally generated hormones in LVH and myocardial failure.
- To discuss the potential for preventing or reversing fibrosis-induced myocardial failure.
Main Methods:
- Review of experimental findings on acquired and genetic arterial hypertension.
- Analysis of the renin-angiotensin-aldosterone system's role in myocardial remodeling.
- Examination of hormonal signals mediating nonmyocyte cell involvement in LVH.
Main Results:
- Hormone-mediated fibroblast proliferation and collagen synthesis lead to myocardial fibrosis.
- Activated renin-angiotensin-aldosterone systems in hypertension influence myocardial structure and failure.
- Experimental strategies to regress excess collagen in LVH have been identified.
Conclusions:
- Nonmyocyte cell alterations, driven by hormones, are central to pathologic LVH and myocardial fibrosis.
- Hormonal systems critically determine myocardial structural changes and the onset of failure in hypertension.
- Further research is needed to elucidate fibrosis mechanisms and assess reversibility of fibrosis-induced myocardial failure in humans.
Abstract:
In both men and women left ventricular hypertrophy (LVH) is the major risk factor associated with the appearance of diastolic and/or systolic myocardial failure. It is not the growth of cardiac myocytes, however, that is responsible for an abnormal structural remodeling of the hypertrophied myocardium in pathologic LVH, but instead, nonmyocyte cells whose behavior and growth are altered by chronic elevations in circulating hormones. Hormone-mediated cardiac fibroblast proliferation and/or enhanced collagen synthesis, for example, account for myocardial fibrosis. The signals mediating nonmyocyte cell involvement in LVH may also involve locally generated hormones having paracrine properties. Herein we review experimental findings pertaining to the reparative and reactive fibrosis of the myocardium seen in various forms of acquired and genetic arterial hypertension, where circulating or tissue renin-angiotensin-aldosterone systems are respectively activated. These hormonal systems determine whether myocardial structure will be altered in arterial hypertension and, accordingly, if myocardial failure ensues. The mechanisms by which these hormones lead to myocardial fibrosis remain to be elucidated and correspondingly will determine if fibrosis can be effectively prevented. At the same time, experimental strategies that regress excess collagen in LVH have been identified, but need to be developed further to determine if myocardial failure, caused by fibrosis, is indeed reversible in humans.