Myocardial Connective Tissue Alterations

Abstract

There is a complex network of collagen throughout the heart. It is composed of a hierarchy of fibrils and fibers ranging from 10 nm to 2–3 microns in diameter. This network can be broken down by ischemia, adriamycin administration, or disulfide administration in laboratory animals. Following loss due to coronary artery ligation, the ischemic area begins bulging within 3 h. General loss of portions of the collagen matrix is induced by intravenous oxidizing glutathione, and results in marked diffuse ventricular dilatation. Generalized collagen loss in the ventricles, as induced by disulfide administration or adriamycin infusion, persists for 6 months at which time evidence of some replacement is visible, and evidence of diffuse fibrosis is present. In humans, cardiac dilatation occurs in a variety of disease states without overstretch of sarcomeres. This presumes rearrangement of the muscle bundles, which can only occur with marked alterations of the collagen matrix. Ventricular dilatation, associated with viral myocarditis or puerperal cardiomyopathy, may persist for months, suggesting the collagen loss, as with the experimental animals, takes many months to repair. The cardiac dilatation may ameliorate, or, in some patients, deteriorate into heart failure. The animal experiments with loss of the collagen matrix, ventricular dilatation, and failure to replace the matrix for many months provide an explanation for persistent cardiac dilatation in various human diseases.

Perturbation of microRNAs in Rat Heart during Chronic Doxorubicin Treatment

“…Cardiac toxicity at a cumulative dose of 12 mg/kg (3 mg/kg/week for 4 weeks) was confirmed by histopathological lesions and altered expression of genomic indicators associated to contraction performance (Myh6, Myh7) and heart failure (Ankrd1/CARP, Nppb) (Figure 2) [28], [29], [30], [31], [32]. In most of the cases the dysregulation of these genes reached a significantly higher level between 2 and 4 weeks of the DOX 3 mg/kg/week dosing regimen.…”

Activation of extracellular matrix metalloproteinases in equine laminitis

“…Other relatively non‐specific circulating proteinase inhibitors, such as alpha‐2 macroglobulin, may also be important for the regulation of the activity of the metalloproteinases in the extracellular matrix. In healthy connective tissues, however, most potential collagenolytic activity is present in a latent form (Caulfield and Wolkowicz 1988, Tyagi and others 1993). Although four of the horses had acute laminitis and two had chronic laminitis, enhanced metalloproteinase activity was demonstrated in the laminar tissues from all six.…”

The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity

“…Further recent review articles cover the role of autophagy [26,27] and mitophagy [28] in DOX cardiotoxicity. Moreover, fibrosis plays a vital part in structural remodelling in DOX cardiotoxicity, initiated through TGFβ signalling, and this has been comprehensively reviewed recently [29]. It is evident that DOX cardiotoxicity is not attributable to one single target, rather, a multitude of proteins and pathways is affected and modulated by DOX.…”