Editorial
Authors: K T Weber
Journal: Cardiovascular Research (1999)

Chronic cardiac failure is a worldwide health problem of recognized for lung, liver and kidney. The heart is no major proportions. It appears most frequently in patients different. Its interstitial compartment is anything but inert with ischemic cardiomyopathy (ICM), an entity that because it contains pluripotent fibroblasts having marked evolves over months following transmural myocardial phenotypic and functional diversity. Phenotypically transinfarction (MI) and is associated with adverse cardiovascuformed fibroblast-like cells, termed myofibroblasts, are lar events, including symptomatic heart failure and sudden involved in tissue repair following MI [11–13]. Importantcardiac death [1,2]. ICM is characterized by an infarcted ly, they remain at sites of repair for years after MI [14]. segment of left ventricular myocardium now scarred. The However it is not merely their persistence, but their infarct scar, a replacement for lost myocytes, rebuilds continued metabolic activity (e.g., expressing fibrillar necrotic myocardium, restores structural integrity, and collagens) that accounts for progressive interstitial fibrosis resists tissue deformation. There is dilatation of the left of an organ and its ultimate failure [15–17]. Regulatory ventricular chamber and impaired systolic performance signals involved in continued collagen turnover of these involving noninfarcted segments of its myocardium and cells are formed de novo (locally) and/or derived from the which appear in the absence of progressive coronary artery circulation [18]. disease or recurrent MI [3–6]. To refine the analysis of cellular and molecular events To decipher the pathophysiologic code leading to proinvolved in tissue repair following MI and to gain insights gressive failure of myocardium in ICM, investigators into signals contributing to the progressive structural addressed its morphologic features finding: an array of remodeling of noninfarcted myocardium that eventuates in cardiac myocyte size, based on the hypertrophy of some ventricular dysfunction in human ICM, investigators and atrophy of other myocytes; a loss of myocytes turned to animal models.Various species have been utilized secondary to necrosis and programmed cell death (apop[19–21]. MI is induced by permanent occlusion of one or tosis); and a structural remodeling of the extracellular more coronary arteries. The nature and rate of repair space by fibrous tissue, related to and also independent of following MI depends on the extent to which perfusion of myocyte loss [7–9]. In the explanted failing heart with injured tissue is maintained by a collateral circulation, ICM, fibrosis remote to the infarct accounts for 70% of all including the delivery of circulating inflammatory cells to observed fibrous tissue and contrasts to infarct scar, which the infarct site. Differences in collateral circulation may represents the remaining 30% [7]. It was concluded that contribute to variations in tissue repair seen between the adverse accumulation of matrix in noninfarcted species, including the appearance of mechanical complicamyocardium is the major component to the adverse tions following MI (e.g., ventricular aneurysm) [21]. structural remodeling found in these hearts. Thus following At the University of Maastricht, ground breaking studies MI, both infarcted and noninfarcted myocardium are of tissue repair have focused on the infarcted rat heart involved in a structural remodeling of myocyte and having a large, transmural anterior MI accompanied by left nonmyocyte compartments. Remote to the infarct an ventricular dilatation and reduced cardiac reserve [22]. In abnormal deposition of fibrillar collagen represents a major remote myocardium (septum and right ventricle), DNA feature of this process. synthesis is increased during week 1 and 2 and involves A progressive interstitial fibrosis of an organ represents the replication of interstitial fibroblasts and endothelial a final common pathway to its failure [10]. The association cells. Pharmacologic intervention further refined the between such fibrosis and impaired function is widely scenario. Proliferation of these nonmyocyte cells is abrogated by an angiotensin converting enzyme (ACE) inhibSee pages 586–593. itor, but not an AT1 receptor antagonist [22,23]. Further-