Troponin T and Plasma Collagen Peptides in Heart Failure

Abstract

The extracellular matrix of the heart is made up of a number of structural proteins including fibrillar collagen, smaller amounts of elastin, laminin, fibronectin, and signaling peptides. The complex collagen 3-dimensional weave, mainly consisting of type I collagen, interconnects individual myocytes through a collagen–integrin–cytoskeletal–myofibril arrangement.1 This network supports cardiac myocytes during contraction and relaxation and also provides a mechanism for translating individual myocyte shortening and force generation into ventricular contraction. It is also responsible for much of the ventricle’s passive diastolic stiffness.2 In both human and animal studies, progressive left ventricular remodeling and dysfunction are associated with significant changes in the extracellular matrix.3–5 Article see p 406 The structural hallmark of prolonged pressure-overload hypertrophy is increased collagen accumulation between individual myocytes and myocyte fascicles (Figure 1).6,7 Thus, the highly organized architecture of the extracellular matrix undergoes significant alterations in collagen structure, composition, and geometry caused by increased collagen synthesis, postsynthetic processing, posttranslational modification, and decreased degradation and turnover. This “reactive” collagen deposition is characterized by both perivascular and interstitial fibrosis.2,8,9 The changes in collagen homeostasis that occur during the development of chronic pressure-overload hypertrophy are directly associated with increased myocardial diastolic stiffness properties, which in turn cause abnormal diastolic filling.7,10,11 Indeed, clinical evidence suggests that progressive extracellular matrix accumulation and diastolic dysfunction are important underlying pathophysiological mechanisms for heart failure in patients with pressure-overload hypertrophy.12,13 Figure 1. Scanning electron micrographs taken from normal nonhuman primate left ventricular myocardium following the induction of pressure-overload hypertrophy (POH). These microscopic studies demonstrated thickening of the collagen weave and overall increased relative content between myocytes with POH. Reproduced with permission.6 In volume-overload hypertrophy because of the persistently elevated preload, a much different pattern of extracellular …