Structural Composition of Myocardial Infarction Scar in Middle-aged Male and Female Rats

Abstract

ArticleSudden obstruction of coronary blood flow causes ischemic death of cardiomyocytes followed by a universal cascade of reparative events (Frangogiannis 2006) leading to infarct healing and scar formation in the heart. Nevertheless, a growing body of evidence from animal studies suggests that females exhibit a different pattern of myocardial infarction (MI) healing and left ventricular (LV) remodeling than males. For instance, post-MI female mice reveal less exaggerated inflammation and enhanced reparative fibrotic response during infarct healing, contributing to a lower rate of cardiac rupture and a lesser degree of LV remodeling in comparison with males (Cavasin et al. 2004;Gao et al. 2005;Fang et al. 2007;Wang F et al. 2007). In addition, despite comparable infarct size and LV cavity dilatation, the thickness of noninfarcted myocardium is less in post-MI female than male rats (Litwin et al. 1999), indicating a smaller increase in compensatory hypertrophy in response to post-MI cardiac remodeling in the females.Although most of these studies were focused on earlier reparative events taking place in male and female hearts during the overlapping phases of MI healing (i.e., inflammatory, proliferative and maturation phases), surprisingly little attention has been paid to providing a comparative assessment of the structural components in a mature scar. However, it has been previously shown that the tissue composition of a mature scar is an important determinant of its mechanical properties (Connelly et al. 1985) and, thereby, can drastically influence overall ventricular performance SummaryThe present study was designed to determine whether the structural composition of the scar in middle-aged post-myocardial infraction (MI) rats is affected by the biological sex of the animals. A large MI was induced in 12-month-old male (M-MI) and female (F-MI) Sprague-Dawley rats by ligation of the left coronary artery. Four weeks after the MI, rats with transmural infarctions, greater than 50% of the left ventricular (LV) free wall, were evaluated. The extent of LV remodeling and fractional volumes of fibrillar collagen (FC), myofibroblasts, vascular smooth muscle (SM) cells, and surviving cardiac myocytes (CM) in the scars were compared between the two sexes. The left ventricle of post-MI male and female rats underwent a similar degree of remodeling as evidenced by the analogous scar thinning ratio (0.46 ± 0.02 vs. 0.42 ± 0.05) and infarct expansion index (1.06 ± 0.07 vs. 1.12 ± 0.08), respectively. Most important, the contents of major structural components of the scar revealed no evident difference between M-MI and F-MI rats (interstitial FC, 80.74 ± 2.08 vs. 82.57 ± 4.53; myofibroblasts, 9.59 ± 1.68 vs. 9.56 ± 1.15; vascular SM cells, 2.27 ± 0.51 vs. 3.38 ± 0.47; and surviving CM, 3.26 ± 0.39 vs. 3.05 ± 0.38, respectively). Our data are the first to demonstrate that biological sex does not influence the structural composition of a mature scar in middleaged post-MI rats. (J Histochem Cytochem 61:833-848, 2013)

The Importance of Biological Sex and Estrogen in Rodent Models of Cardiovascular Health and Disease

“…132 In a similar study that analyzed scar composition four weeks post-MI, males developed larger MI scars than females, but the overall structural composition of the scars was not different between sexes. 133 Aged male and female rats displayed similar patterns of overall LV remodeling, but differences were apparent in regional cardiomyocyte hypertrophy and arteriole expansion four weeks post-MI. 134 Together, these studies demonstrate that sex differences do exist in rodents with experimental MI, but inconsistencies are observed between mice and rats.…”

A dual flip angle 3D bSSFP magnetization transfer‐like method to differentiate between recent and old myocardial infarction

“…Collagen, the main protein of the extracellular myocardial matrix, is a major source of heightened MTR due to abundant hydroxyl amine groups and accounts for a fractional volume (measured by histomorphometry) in the range of 3% with picrosirius red staining in rat papillary muscle as well as in normal human hearts . In experimental chronic infarct scar in rats, the fractional volume of fibrillar collagen rises dramatically to ∼80% and collagen constitutes up to 70% of the histological sample in the transplanted heart of a hypertrophic cardiomyopathy patient . Thus, in the study of Vandsburger et al, performed on seven rats at 9.4T, MTR increased from ∼30 to 45% in the fibrotic scar tissue as demonstrated by Masson trichrome staining 21 days after surgically induced MI .…”

Sex-related differences in intrinsic myocardial properties influence cardiac function in middle-aged rats during infarction-induced left ventricular remodeling

“…Using these measurements, the following global LV indices were computed: (1) LV cavity diameter to septum thickness ratio; (2) the scar thinning ratio (the ratio between average thickness of the scar and the average thickness of the septum); and (3) the infarct expansion index ([LV cavity area/LV area] × [septal wall thickness/scar thickness]), as previously reported (Bogatyryov et al. ; Dedkov et al. ).…”