摘要
The exploration of coronary microcirculatory dysfunction in diabetes has accelerated in recent years.Cardiac function is compromised in diabetes.Diabetic patients manifest accelerated atherosclerosis in coronary arteries.These data are confirmed in diabetic animal mod-els,where lesions of small coronary arteries have been described.These concepts are epitomized in the classic microvascular complications of diabetes,i.e.blindness,kidney failure and distal dry gangrene.Most importantly,accumulating data indicate that insights gained from the link between inflammation and diabetes can yield predictive and prognostic information of considerable clinical utility.This review summarizes the evidence for the predisposing factors and the mechanisms involved in diabetes,and assesses the current state of knowledge regarding the triggers for inflammation in this disease.We evaluate the roles of hyperglycemia,oxidative stress,polyol pathway,protein kinase C,advanced glycation end products,insulin resistance,peroxisome proliferator-activated receptor-γ,inflammation,and diabetic cardiomyopathy as a "stem cell disease".Furthermore,we discuss the mechanisms responsible for impaired coronary arteriole function.Finally,we consider how new insights in diabetes may provide innovative therapeutic strategies.
The exploration of coronary microcirculatory dysfunction in diabetes has accelerated in recent years. Cardiac function is compromised in diabetes. Diabetic patients manifest accelerated atherosclerosis in coronary arteries. These data are confirmed in diabetic animal models, where lesions of small coronary arteries have been described. These concepts are epitomized in the classic microvascular complications of diabetes, i.e. blindness, kidney failure and distal dry gangrene. Most importantly, accumulating data indicate that insights gained from the link between inflammation and diabetes can yield predictive and prognostic information of considerable clinical utility. This review summarizes the evidence for the predisposing factors and the mechanisms involved in diabetes, and assesses the current state of knowledge regarding the triggers for inflammation in this disease. We evaluate the roles of hyperglycemia, oxidative stress, polyol pathway, protein kinase C, advanced glycation end products, insulin resistance, peroxisome proliferator-activated receptor-γ, inflammation, and diabetic cardiomyopathy as a “stem cell disease”. Furthermore, we discuss the mechanisms responsible for impaired coronary arteriole function. Finally, we consider how new insights in diabetes may provide innovative therapeutic strategies.
基金
Supported by Grants from Pfizer Atorvastatin Research Award,No. 2004-37
American Heart Association SDG,No. 110350047A
NIH Grants,No. RO1 HL077566 and RO1 HL085119 to Zhang C
