Changes in collagenase and collagen gene expression after induction of aortocaval fistula in rats

Abstract

Progressive ventricular dilatation commonly accompanies the transition to overt failure in chronically overloaded hearts; however, only recently have studies begun to elucidate underlying molecular alterations. In particular, the potential role of altered myocardial expression of the procollagenase gene in this process has not previously been examined. Biventricular hypertrophy and dilatation were produced in rats by creating an abdominal aortocaval fistula. The time courses of changes in expression of collagen I and III genes and of the procollagenase gene (matrix metalloproteinase-1, MMP-1) were assessed by Northern blot hybridization. Expression of all three genes increased promptly; however, collagenase gene expression peaked much earlier (8 h) than did expression of either of the collagen genes (7 days), and all returned to baseline levels by 45 days. These data corroborate earlier reports of increased collagen gene expression in this model, but more importantly, they provide the first evidence of concurrent activation of collagenase gene expression, suggesting that enhancement of collagen degradation may be a prerequisite for structural cardiac dilatation.

Effects of Pressure Overload on Extracellular Matrix Expression in the Heart of the Atrial Natriuretic Peptide–Null Mouse

“…Collagen expression is increased and the ratio of the 2 major subtypes is reversed in the setting of pressure-and volume-induced cardiac hypertrophy (ie, collagen IϾIII in resting heart; IIIϾI in hypertrophic heart). 33,34 In this study, robust increases in mRNA levels of collagen I and III were seen in LV of Nppa Ϫ/Ϫ mice after TAC; increases were much more modest in the Nppa ϩ/ϩ mouse ( Figures 3B and 3C). Total collagen protein, assessed by Masson's trichrome staining, was much more abundant in the LV of TAC Nppa -/-mice than in the other treatment groups ( Figure 6B).…”

Different Growth Factor Activation in the Right and Left Ventricles in Experimental Volume Overload

“…A selective increase in collagen concentration in the right myocardium was previously observed in small animals with aortocaval fistula 9,10,15 and in human congenital heart disease with mixed pressure and volume right ventricular overload. 39 However, because of the treatment protocol and the difficulty to perform accurate dose findings in small animals, previous studies failed to observe changes in cardiac collagen in animals treated with Ang II antagonists.…”

“…7 Increased collagen accumulation characterizes concentric hypertrophy of experimental pressure overload, 8 whereas no significant changes in fibrillar collagen content have been observed in experimental volume-induced eccentric hypertrophy. 9,10 The pattern of growth factor gene expression is then finally modified by the transition from hypertrophy to failure with enhanced angiotensin II (Ang II) formation and reduced IGF-I expression. 11 Thus, the expression of local growth factors appears to participate in the regulation of the type of cardiac hypertrophy and to characterize the transition to failure.…”

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

“…Representa-tive scanning electron micrographs taken from a wellestablished model of canine mitral regurgitation (88,409) are shown in Figure 3 and demonstrate the profound differences in ECM structure and composition compared with normal myocardium and that of POH. In rodent models of aortocaval fistula, another form of VOH, a similar pattern of LV remodeling and changes in the ECM structure and composition have been reported (96,124,127,244,274,484). In both forms of LVH, a loss of normal ECM structure and function occurs which suggests that alterations in ECM degradative processes have occurred.…”

“…The generic or common names can be a source of confusion, and therefore, the specific MMP type under question is often referred to by number. For example, MMP-13 has been referred to as rodent collagenase, since this is the primary collagenase found in rodent myocardial samples (96,227,228,334,504). However, robust levels of MMP-13 have been reported in large animal and human myocardial specimens (39,348,503).…”