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 arter...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.展开更多
Endothelial progenitor cells(EPCs)are a heterogeneous population of cells that are provided by the bone marrow and other adult tissue in both animals and humans.They express both hematopoietic and endothelial surface ...Endothelial progenitor cells(EPCs)are a heterogeneous population of cells that are provided by the bone marrow and other adult tissue in both animals and humans.They express both hematopoietic and endothelial surface markers,which challenge the classic dogma that the presumed differentiation of cells into angioblasts and subsequent endothelial and vascular differentiation occurred exclusively in embryonic development.This breakthrough stimulated research to understand the mechanism(s)underlying their physiologic function to allow development of new therapeutic options.One focus has been on their ability to form new vessels in injured tissues,and another has been on their ability to repair endothelial damage and restore both monolayer integrity and endothelial function in denuded vessels.Moreover,measures of their density have been shown to be a better predictor of cardiovascular events,both in healthy and coronary artery disease populations than the classical tools used in the clinic to evaluate the risk stratification.In the present paper we review the effects of EPCs on revascularization and endothelial repair in animal models and human studies,in an attempt to better understand their function,which may lead to potential advancement in clinical management.展开更多
基金Supported by Grants from Pfizer Atorvastatin Research Award,No. 2004-37American Heart Association SDG,No. 110350047ANIH Grants,No. RO1 HL077566 and RO1 HL085119 to Zhang C
文摘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.
基金Supported by Grants from American Heart Association grant-in-aid,No.0455435BAmerican Heart Association SDG,No. 110350047ANIH Grant No.RO1-HL077566 and No.RO1-HL085119 to Zhang C
文摘Endothelial progenitor cells(EPCs)are a heterogeneous population of cells that are provided by the bone marrow and other adult tissue in both animals and humans.They express both hematopoietic and endothelial surface markers,which challenge the classic dogma that the presumed differentiation of cells into angioblasts and subsequent endothelial and vascular differentiation occurred exclusively in embryonic development.This breakthrough stimulated research to understand the mechanism(s)underlying their physiologic function to allow development of new therapeutic options.One focus has been on their ability to form new vessels in injured tissues,and another has been on their ability to repair endothelial damage and restore both monolayer integrity and endothelial function in denuded vessels.Moreover,measures of their density have been shown to be a better predictor of cardiovascular events,both in healthy and coronary artery disease populations than the classical tools used in the clinic to evaluate the risk stratification.In the present paper we review the effects of EPCs on revascularization and endothelial repair in animal models and human studies,in an attempt to better understand their function,which may lead to potential advancement in clinical management.
