Targeting Pathological Remodeling

The myocardium is composed of cardiac myocytes, which are tethered within an extracellular scaffolding of fibrillar collagen. Myocytes are large; they occupy a major portion of tissue space. However, they number only a third of all cells in the myocardium; noncardiomyocytes constitute the remaining two-thirds of cells and include endothelial and vascular smooth muscle cells of the intramural coronary circulation and fibroblasts located in interstitial and perivascular spaces.1 2 Ventricular hypertrophy is based on the growth of cardiac myocytes, which may or may not be accompanied by other iterations in tissue structure. In athletes, the growth of muscular and nonmuscular compartments of the heart are proportionate; tissue homogeneity is preserved. Such adaptive hypertrophy contributes to enhanced cardiac performance.The myocardial mass that accompanies exercise training is comparable to the left ventricular hypertrophy (LVH) seen in patients with essential hypertension of mild to marked severity.3 In hypertensive heart disease (HHD), however, tissue homogeneity gives way to heterogeneity because the disproportionate involvement of noncardiomyocyte cells accounts for the pathological remodeling of tissue structure.2 Fibroblasts, for example, contribute to a perivascular fibrosis of intramural arteries and arterioles, which over time extends into contiguous interstitial space. This perivascular/interstitial fibrosis is based neither on myocyte growth nor necrosis; it represents reactive fibrosis. Medial thickening of these vessels involves hypertrophy and/or hyperplasia of vascular smooth muscle cells.4 Microscopic scarring (a reparative fibrosis) replaces myocytes lost to necrosis (apoptosis is not followed by fibrosis). Together with the hypertrophy of left ventricular myocytes, these iterations in tissue structure in HHD create a pathological hypertrophy that predisposes to an enhanced risk of adverse cardiovascular events, including myocardial infarction, diastolic and/or systolic ventricular dysfunction, symptomatic heart failure, and arrhythmias.5 6 It is not the quantity, but rather the quality, of myocardium that distinguishes HHD from …