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Structural basis for pathologic left ventricular hypertrophy
1Department of Internal Medicine, University of Missouri-Columbia School of Medicine 65212.
Insights
Chronic high aldosterone levels, not just heart muscle growth, drive myocardial fibrosis and lead to heart failure. Understanding this process may reverse pathological left ventricular hypertrophy (LVH).
Area of Science:
- Cardiovascular Biology
- Pathophysiology
- Cardiac Remodeling
Background:
- Left ventricular hypertrophy (LVH) is a significant risk factor for congestive heart failure.
- While hypertrophied myocytes are key, myocardial fibrosis (connective tissue accumulation) also impairs cardiac function.
- Cardiac fibroblasts play a crucial role in collagen metabolism and pathological LVH.
Purpose of the Study:
- To investigate the role of circulating substances in myocardial fibrosis beyond direct pressure overload.
- To explore the link between aldosterone levels and the development of interstitial fibrosis.
- To understand how fibrosis impacts diastolic and systolic ventricular function in LVH.
Main Methods:
- In vivo studies examining the hypothesis of a circulating substance affecting both ventricles.
- Analysis of myocardial structure and function in experimental hypertension models.
- Assessment of the relationship between aldosterone levels, sodium intake, and myocardial fibrosis.
Main Results:
- Chronic elevation of circulating aldosterone, relative to sodium intake, is associated with myocardial fibrosis.
- Myocardial fibrosis initially impairs diastolic function and subsequently affects systolic function.
- Reactive fibrosis occurs in both pressure-overloaded and normotensive ventricles, suggesting a circulating factor.
Conclusions:
- Aldosterone-mediated myocardial fibrosis is a critical factor in pathological left ventricular hypertrophy (LVH) and heart failure.
- Fibrosis adversely affects both diastolic and systolic ventricular performance.
- Further research into the mechanisms of fibroblast collagen metabolism could lead to treatments for fibrosis and LVH.
Abstract:
Left ventricular hypertrophy (LVH) is a major risk factor associated with the emergence of symptomatic congestive heart failure. Cardiac myocyte excitation-contraction coupling has been the biochemical focus in the search for insights into the impaired contractility, relaxation, and stiffness of the hypertrophied myocardium. Although hypertrophied myocytes are the hallmark of LVH, other aspects of myocardial structure may be altered to impair pump function--specifically an abnormal accumulation of connective tissue (interstitial fibrosis). Cardiac fibroblasts, which are nonmyocyte cells of the cardiac interstitium, synthesize and degrade collagen and, therefore, represent an important determinant of pathologic LVH. Significantly, this reactive fibrosis has been found not only in the pressure-overloaded hypertrophied left ventricle but also in the normotensive, nonhypertrophied right ventricle of animals with experimental hypertension. These findings suggest the involvement of a circulating substance that has access to the coronary circulation common to both ventricles. Based on in vivo studies that examined this hypothesis, it can be concluded that chronic elevation of circulating aldosterone, relative to sodium intake, is associated with myocardial fibrosis, which initially adversely alters diastolic function and ultimately systolic ventricular function. The mechanisms by which fibroblast collagen metabolism is invoked in this setting are under investigation. Elucidation of these mechanisms may prepare the way to the prevention as well as the reversal of myocardial fibrosis and, in turn, of pathologic LVH.