Extracellular matrix gene expression correlates to left ventricular mass index after surgical induction of left ventricular hypertrophy

Abstract

The cardiac extracellular matrix (ECM) is a dynamic entity maintaining the structural and functional properties of the myocardium. Little is known about alterations in ECM regulation during controlled induction of compensated left ventricular hypertrophy (LVH) using experimental aortic stenosis.

Fifteen growing sheep received supra-coronary banding at an age of 7 ± 1 months whereas 10 age-matched sheep served as the control group (C). Explantation of the hearts was performed 8.3 ± 1 months after banding. Gene sequences for sheep matrix metalloproteinase (MMP)-1,-2,-3,-9 and tissue inhibitors (TIMP)-1,-2,-3 were isolated and cloned. Then mRNA and protein gene expression analyses were performed.

Concentric LVH with no evidence of heart failure was diagnosed at explantation. Left ventricular mass index (LVMI) was 150 ± 33 g/m² (LVH) versus 88 ± 23 (C) and 82 ± 21 (baseline) (p < 0.01 versus LVH). Parallel to LVH there was a significant increase in mRNA and protein expression for MMP-1,-2,-3,-9 and for TIMP-1,-2 whereas there was a significant decrease in TIMP-3 gene expression. A close correlation between changes in LVMI and ECM gene expression was found.

Compensated LVH goes along with a significant modification of MMP and TIMP gene expression. Alterations in ECM gene expression may be part of the adaptive process during left ventricular remodeling.