Altered Microvasculature Is Involved in Remodeling Processes in Cardiomyopathic Hamsters

Abstract

The cardiomyopathic hamster (BIO TO2) is a well-established model of heart failure. Deterioration of cardiac function in BIO TO2 is attributed to a defect in δ-sarcoglycan, whereas cardiac dysfunction in δ-sarcoglycan knockout mice is caused by microvascular abnormalities. We examined the relation between cardiac function and the microvasculature, including angiogenic factors, in BIO TO2. Methods and Results: At the age of 5 weeks, percent fractional shortening (%FS) and positive rate of change in left ventricular pressure over time (dP/dt max) were lower in BIO TO2 than in age-matched F1B controls. Capillary density, capillary/myocyte (CM) ratio, capillary domain area (CDA), and myocyte density were similar between BIO TO2 and F1B controls. At the ages of 13 and 20 weeks, BIO had significantly lower capillary and myocyte densities and a significantly higher CM ratio and CDA. Myocyte density positively correlated with %FS and dP/dt max. There were no significant differences in mRNA expression for VEGF, Flt-1, angiopoietin-1, or angiopoietin-2 between BIO TO2 and F1B control. Conclusion: Progressive myocyte loss is responsible for deterioration of cardiac function in BIO TO2. The impaired neovascularization may be involved in the progress of cardiac remodeling in cardiomyopathic hamsters.