Effects of adipocyte-derived cytokines on endothelial functions: implication of vascular disease.
Adipose tissue has recently emerged as an active endocrine organ that secretes a variety of metabolically important substances, collectively called adipocytokines or adipokines. In this review we summarize the effects of the adipokines leptin, adiponectin, and resistin on the vasculature and their potential role for pathogenesis of vascular disease. Leptin is associated with arterial wall thickness, decreased vessel distensibility, and elevated C reactive protein (CRP) levels. Leptin possesses procoagulant and antifibrinolytic properties, and it promotes thrombus and atheroma formation, probably through the leptin receptors by promoting vascular inflammation, proliferation, and calcification, and by increasing oxidative stress. Research for development of pharmacologic antagonism for the leptin receptor is currently under way. Adiponectin inhibits the expression of the adhesion molecules ICAM-1, VCAM-1, and P selectin. Therefore, it interferes with monocyte adherence to endothelial cells and their subsequent migration to the subendothelial space, one of the initial events in the development of atherosclerosis. Adiponectin also inhibits the transformation of macrophages to foam cells in vitro and decreases their phagocytic activity. Resistin, discovered in 2001, represents the newest of the adipokines and was named for its ability to promote insulin resistance. Resistin increases the expression of the adhesion molecules VCAM-1 and ICAM-1, up-regulates the monocyte chemoattractant chemokine-1, and promotes endothelial cell activation via ET-1 release. Although many aspects of its function need further clarification, it appears that resistin will add significantly to our knowledge of the pathophysiology of vascular disease and the metabolic syndrome.
Kougias
Panagiotis
P
Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Chai
Hong
H
Lin
Peter H
PH
Yao
Qizhi
Q
Lumsden
Alan B
AB
Chen
Changyi
C
D052242:Adiponectin; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D004730:Endothelium, Vascular / Q000502:physiology*; D006729:Hormones, Ectopic / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D020738:Leptin / Q000502:physiology*; D052243:Resistin; D013927:Thrombosis / Q000209:etiology; D014652:Vascular Diseases / Q000209:etiology*
D052242:Adiponectin; D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; C499624:RETN protein, human; D052243:Resistin