Inflammation and neovascularization in diabetic atherosclerosis.
Diabetes mellitus, the major cardiovascular risk factor, accentuates the inflammation and neovascularization processes leading to enhanced progression of atherosclerotic complications. Inflammation in diabetes mellitus is the key initiator of atherosclerotic process, which results in acute coronary events. Atherosclerosis evolves from the endothelial cell dysfunction and succeeding entry of hemodynamically derived leukocytes by migration, activation and production of lipid gruel leading to atheromatous plaque progression and subsequent regression. Diabetic plaque progression is associated with increased neovascularization, which is a nature's compliment in the sustenance of plaque growth by its nutrient supply. Neovessels may act as conduit for lipid debridment and alternative channel for inflammatory process. In addition, neovascularization induces intra-plaque hemorrhage due to the fragility of the neovessels and associated inflammation, resulting in plaque instability. The intra-plaque hemorrhage is a detrimental base, which begets the progress of atheroma by inducing oxidative stress and endothelial dysfunction. Intra-plaque hemorrhage is increased in diabetes with an associated increase in hemoglobin-haptoglobin complex (Hb-Hp2-2), which further induces oxidative stress and endothelial cell dysfunction. We conclude that inflammation and neovascularization of the plaque may act as major mechanism augmenting plaque instability in diabetes mellitus.
Purushothaman
K R
KR
Zena and Michael A. Wiener Cardiovascular Institute and The Marie-Jose and Henry R. Kravis Cardiovascular Health Center, The Mount Sinai School of Medicine, Box 1030, New York, NY, USA. purushothaman.kothandaraman@msnyuhealth.org
Meerarani
P
P
Moreno
P R
PR
D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D003925:Diabetic Angiopathies / Q000473:pathology*; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D023084:alpha-Defensins / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D023084:alpha-Defensins; C406416:human neutrophil peptide 2