Abstract
BackgroundAn increasing body of evidence indicates that left ventricular (LV) remodeling, especially the degree of reactive myocardial hypertrophy after myocardial infarction (MI), differs in males and females. Surprisingly, to date, the sex-specific post-MI alterations of the coronary vasculature remain undetermined. Therefore, we tested the hypothesis that adaptive coronary arteriolar and capillary modifications occurring in response to reactive myocyte hypertrophy differ between middle-aged male and female post-MI rats.MethodsA 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 surgery, rats with transmural infarctions, greater than 50% of the LV free wall (FW), were evaluated. Sham-operated male (M-Sham) and female (F-Sham) rats served as an age-matched controls.ResultsF-MI and M-MI rats had similar sized infarcts (61.3% ± 3.9% vs. 61.5% ± 1.2%) and scale of LV remodeling, as indicated analogous remodeling indices (1.41 ± 0.11 vs. 1.39 ± 0.09). The degree of reactive post-MI myocardial hypertrophy was adequate to normalize LV weight-to-body weight ratio in both sexes; however, the F-MI rats, in contrast to males, showed no myocyte enlargement in the LVFW epimyocardium. At the same time, a greater than 50% expansion of myocyte area in the male epimyocardium and in the female endomyocardium was accompanied by a 23% (P < 0.05) increase in capillary-to-myocyte ratio, indicative of adaptive angiogenesis. Based on arteriolar length density in post-MI hearts, the resistance vessels grew in the male LVFW as well as the septum by 24% and 29%, respectively. In contrast, in females, a significant (30%) expansion of arteriolar bed was limited only to the LVFW. Moreover, in F-MI rats, the enlargement of the arteriolar bed occurred predominantly in the vessels with diameters <30 μm, whereas in M-MI rats, a substantial (two- to threefold) increase in the density of larger arterioles (30 to 50 μm in diameter) was also documented.ConclusionOur data reveal that while both sexes have a relatively similar pattern of global LV remodeling and adaptive angiogenesis in response to a large MI, male and female middle-aged rats differ markedly in the regional scale of reactive cardiac myocyte hypertrophy and adaptive arteriogenesis.
Highlights
An increasing body of evidence indicates that left ventricular (LV) remodeling, especially the degree of reactive myocardial hypertrophy after myocardial infarction (MI), differs in males and females
Considering the fact that middle-aged female and male rats had significantly different body weights, left and right ventricular weights as well as LV chamber dimensions (Table 1), our main emphasis was to conduct side-by-side comparison of sex-specific adaptations that occurred in the left ventricle of each sex group during cardiac remodeling triggered by a large transmural MI
The loss of cardiac myocytes was compensated by LV hypertrophy in both post-MI groups, as indicated unchanged LV weight-to-body weight ratios, that were similar to a corresponding group of sham rats
Summary
An increasing body of evidence indicates that left ventricular (LV) remodeling, especially the degree of reactive myocardial hypertrophy after myocardial infarction (MI), differs in males and females. Female rats and mice with a large transmural MI had less compensatory hypertrophy in noninfarcted LV regions than did males [12,13,14] In concert with these experimental data, studies on humans have demonstrated that women with LV dysfunction, caused in part by previous MI, were characterized by a smaller increase in LV mass compared to their respective male counterparts [15,16]. Despite the fact that males and females differ markedly in the extent of post-MI compensatory myocardial growth, there are no published studies investigating the degree of the adaptive coronary vessel growth between the sexes
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