This study was conducted to determine the relationship between dysglycemia and the coronary artery vasa vasorum density. RESEARCH DESIGN AND METHODSThe left anterior descending coronary artery was removed from 57 deceased individuals during autopsy, and the capillaries in the vessel wall were identified using fluorescent immunohistochemical staining. HbA 1c was determined in postmortem whole blood for each individual. The density of the vasa vasorum in the intima-media and the adventitia was manually quantified and recorded by readers unaware of the individual's other characteristics. RESULTSThe individuals with diabetes had a lower density of the coronary vasa vasorum than those without diabetes. The higher the HbA 1c , the lower the density of these vessels in the adventitia and entire vessel wall. CONCLUSIONSDysglycemia-induced damage to the vasa vasorum may promote ischemic heart disease in people with diabetes.Diabetes promotes retinal, renal, neurologic, vascular, cardiac, and other organ damage. Although many reasons for this have been suggested, dysglycemia-mediated vasculopenia due to capillary damage in various tissues would provide an overarching explanation. In the walls of medium to large arteries, these damaged capillary beds would be the vasa vasorum (1), a possibility supported by animal models (2) and in vivo measurements in humans (3,4).If the above hypothesis is true, the density of the vasa vasorum should be reduced in the coronary arteries of people with diabetes. This cross-sectional autopsy study was therefore conducted to compare the coronary artery vasa vasorum in individuals with normal versus high HbA 1c at the time of death and to assess the relationship between HbA 1c and vasa vasorum density. RESEARCH DESIGN AND METHODSDeceased individuals undergoing forensic autopsy whose families consented to a full or limited postmortem examination were included if they were aged 50 or older, their coronary arteries could be sectioned and stained, a postmortem blood sample was available, and the autopsy occurred during the pathologist's (V.N.) working hours. Age, sex, history of diabetes, and cause of death were collected, and a postmortem whole-blood sample was sent for HbA 1c . The study was approved by the Research Ethics Board at Hamilton Health Sciences and McMaster University.

Diabetic patients have a twofold to fourfold increased risk of cardiovascular disease. Despite a vast amount of research, the underlying mechanisms that predispose individuals with diabetes to the development of cardiovascular disease are unclear. To further our understanding of how diabetes promotes atherosclerosis, we have established, characterized, and manipulated a new model of hyperglycemia-induced atherosclerosis: the apolipoprotein E-deficient (ApoE(-/-)):Ins2(+/Akita) mouse. All mice were fed a standard chow diet. Male ApoE(-/-):Ins2(+/Akita) mice developed chronic hyperglycemia, which significantly accelerated atherosclerosis. Female ApoE(-/-):Ins2(+/Akita) mice presented hyperglycemia that normalized by 15 weeks of age. Despite the transient hyperglycemia, advanced atherosclerosis was observed at 15 weeks of age compared with ApoE(-/-) females. To better understand these differences, subsets of mice were castrated or ovariectomized at 5 weeks of age. Castrated ApoE(-/-):Ins2(+/Akita) mice showed a reduction in blood glucose levels that correlated with the amelioration of atherosclerosis. Interestingly, castrated normoglycemic ApoE(-/-) mice developed larger atherosclerotic lesions than sham-operated on controls. Ovariectomized ApoE(-/-):Ins2(+/Akita) mice presented chronic hyperglycemia, and atherosclerosis appeared to be advanced. We have characterized the distinctive sex-specific phenotypes exhibited by the ApoE(-/-):Ins2(+/Akita) mouse model and present evidence for the action of sex hormones on pancreatic β-cell function and the vasculature that affect the regulation of blood glucose levels and the development of atherosclerosis. This model will provide a test bed to further delineate these effects.