Left ventricular hypertrophy (LVH) is the major risk factor associated with
myocardial failure. An explanation for why a presumptive adaptation such as LVH would prove pathological has been elusive. Insights into the impairment in contractility of the hypertrophied myocardium have been sought in the biochemistry of cardiac myocyte contraction. Equally compelling is a consideration of abnormalities in myocardial structure that impair organ contractile function while preserving myocyte contractility. For example, in the LVH that accompanies
hypertension, the extracellular space is frequently the site of an abnormal accumulation of
fibrillar collagen. This reactive and progressive interstitial and perivascular
fibrosis accounts for abnormal myocardial stiffness and ultimately
ventricular dysfunction and is likely a result of cardiac fibroblast growth and enhanced
collagen synthesis. The disproportionate involvement of this nonmyocyte cell, however, is not a uniform accompaniment to myocyte
hypertrophy and LVH, suggesting that the growth of myocyte and nonmyocyte cells is independent of each other. This has now been demonstrated in in vivo studies of experimental
hypertension in which the abnormal fibrous tissue response was found in the hypertensive, hypertrophied left ventricle as well as in the normotensive, nonhypertrophied right ventricle. These findings further suggest that a circulating substance that gained access to the common coronary circulation of the ventricles was involved. This hypothesis has been tested in various animal models in which plasma concentrations of
angiotensin II and
aldosterone were varied. Based on morphometric and morphological findings, it can be concluded that arterial
hypertension (i.e., an elevation in coronary perfusion pressure) together with elevated circulating
aldosterone are associated with cardiac fibroblast involvement and the resultant heterogeneity in tissue structure. Nonmyocyte cells of the cardiac interstitium represent an important determinant of pathological LVH. The mechanisms that invoke short- (e.g.,
collagen metabolism) and long-term (e.g., mitosis) responses of cardiac fibroblasts require further investigation and integration of in vitro with in vivo studies. The stage is set, however, to prevent pathological LVH resulting from myocardial
fibrosis as well as to reverse it.