Surgical reinforcement alters collagen alignment and turnover in healing myocardial infarcts

Abstract

Previous studies have suggested that the composition and global mechanical properties of the scar tissue that forms after a myocardial infarction (MI) are key determinants of long-term survival, and emerging therapies such as biomaterial injection are designed in part to alter those mechanical properties. However, recent evidence suggests that local mechanics regulate scar formation post-MI, so that perturbing infarct mechanics could have unexpected consequences. We therefore tested the effect of changes in local mechanical environment on scar collagen turnover, accumulation, and alignment in 77 Sprague-Dawley rats at 1, 2, 3 and 6 wk post-MI by sewing a Dacron patch to the epicardium to eliminate circumferential strain while permitting continued longitudinal stretching with each heart beat. We found that collagen in healing infarcts aligned parallel to regional strain and perpendicular to the preinfarction muscle and collagen fiber direction, strongly supporting our hypothesis that mechanical environment is the primary determinant of scar collagen alignment. Mechanical reinforcement reduced levels of carboxy-terminal propeptide of type I procollagen (PICP; a biomarker for collagen synthesis) in samples collected by microdialysis significantly, particularly in the first 2 wk. Reinforcement also reduced carboxy-terminal telopeptide of type I collagen (ICTP; a biomarker for collagen degradation), particularly at later time points. These alterations in collagen turnover produced no change in collagen area fraction as measured by histology but significantly reduced wall thickness in the reinforced scars compared with untreated controls. Our findings confirm the importance of regional mechanics in regulating scar formation after infarction and highlight the potential for therapies that reduce stretch to also reduce wall thickness in healing infarcts. NEW & NOTEWORTHY This study shows that therapies such as surgical reinforcement, which reduce stretch in healing infarcts, can also reduce collagen synthesis and wall thickness and modify collagen alignment in postinfarction scars.