Heart morphology in Zucker-obese rats

Obesity represents the central and causal component of metabolic syndrome (MetS), which is a growing medical challenge in western countries as a result of changes in lifestyle. Obesity is also associated with an increased incidence of hypertension and a consequent increase in cardiovascular disease risk. In animal models of diet-induced obesity, endothelial inflammatory activa-tion, evident from adhesion molecule expression, appears to be the earliest manifestation of vascular and cardiac damage. The intercellular adhesion molecule-1 (ICAM-1) is a member of the immu-noglobulin (Ig) superfamily which is present on the surface of several other cell types, including endothelial cells. Adhesion molecules [e.g., ICAM-1, vascular cell adhesion molecule 1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1)] if in contact with an activated endothelium could rep-resent attractive targets for delivery of drugs and imaging probes to vascular pathological sites. The present study was designed to investigate, with morphological, immunochemical and immunohistochemical techniques, the alteration of heart and coronary arteries of the Obese Zucker rats (OZR) compared to the lean Zucker rats (LZRs). The OZRs, with a mutation in leptin receptors, represent a model of Type II diabetes mellitus, characterized by the presence of obesity, hyperglycemia, hyperinsulinemia, hyperlipidemia and moderate hypertension similar to MetS. The heart of OZRs of 12, 16 and 20 weeks was processed for the morphological analysis and immuhistochemical investigations for ICAM-1, VCAM-1 and PECAM-1 and the pro-inflammatory cytokines (IL-1, IL-6 and TNF-). The heart of the OZRs at the different age, developed ventricular hypertrophy, characterized by increase size of cardiomyocytes but not fibrosis compared to LZRs. This phenomenon was more evident in 20-weeks-old OZRs. VCAM-1 was more expressed in the coronary arteries compared to the other adhesion molecules, and increased in the OZRs of 20-weeks of age. In the same age, IL-6 expression was significantly increased. These results suggest that the obesity leads to a cardiac changes and coronary inflammation. Actually, myocardial vascular inflammation, induced by metabolic comorbidities, could be an important contributor to development of heart failure. A protective strategies may be concern both body weight loss and the countering metabolic alterations induced by obesity.