(Circulation. 2000;102:1342.)
© 2000 American Heart Association, Inc.
Editorial |
Targeting Pathological Remodeling
Concepts of Cardioprotection and Reparation
From the Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, Memphis.
Correspondence to Karl T. Weber, MD, Division of Cardiovascular Diseases, University of Tennessee Health Science Center, Room 353 Dobbs Research Institute, 951 Court Avenue, Memphis, TN 38163. E-mail KTWeber@utmem.edu
Key Words: Editorials • hypertrophy • hypertension • fibrosis • collagen • angiotensin
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
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