New aspects in the pathogenesis of diabetic atherothrombosis
Pedro R. Moreno, MD*, ,* and
Valentin Fuster, MD, PhD*
* Zena and Michael Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York
Gill Heart Institute, University of Kentucky, Lexington, Kentucky
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Figure 1 Age-specific prevalence of the metabolic syndrome among 8,814 U.S. adults aged at least 20 years of age, by gender, National Health and Nutrition Examination Survey III, 1988 to 1994. Modified with permission from Zimmet et al. (8).
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Figure 2 Age-adjusted prevalence of coronary heart disease (CHD) in the U.S. population over 50 years of age categorized by presence of metabolic syndrome (MS) and diabetes mellitus (DM). Combinations of metabolic syndrome and diabetes mellitus status are shown. Reprinted with permission from Alexander et al. (11).
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Figure 3 Several factors such as altered nutrition, inactivity, age, fetal metabolic programming, and genetic propensity are known activators of the innate immune system. Cytokine production leads to insulin resistance, type 2 diabetes, and other components of the metabolic syndrome, such as dyslipidemia. Activated innate immunity is a possible common antecedent of both type 2 diabetes and atherosclerosis. IL-6 = interleukin-6; TNF = tumor necrosis factor-alpha. Modified with permission from Pickup (12).
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Figure 4 (Left) Increased percent macrophage area in coronary tissue from patients with diabetes mellitus versus tissue from patients without diabetes. (Right) Photomicrographs of coronary atherectomy tissue immunostained with antihuman pan-macrophage antibody. Larger macrophage content is seen in coronary tissue from a patient with diabetes mellitus (A) than in coronary tissue from a patient without diabetes (B). Reprinted with permission from Moreno PR, et al. Circulation 2000;102:2180–4.
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Figure 5 Rupture of the internal elastic lamina (IEL). Photomicrograph of advanced aortic diabetic atherosclerosis illustrating an aggressive inflammatory pattern at the intimomedial junction. The continuity of IEL (left side) is interrupted (right side) where multiple round-nuclei inflammatory cells are observed, expanding the atherosclerotic process from the tunica intima into the tunica media (elastic trichrome stain). Courtesy of Dr. K-Raman Purushothaman (Mount Sinai Medical Center, New York, New York).
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Figure 6 Photomicrographs of microvessels identified by double-label immunochemistry stain using CD34 and CD68/CD3 (left) and CD34 and smooth-muscle actin (right). (A) Microvessels are labeled with blue chromogen and macrophages/T lymphocytes are labeled with a red chromogen at the base of the plaque. (B) Tunica media microvessels are labeled with a purple chromogen and the smooth-muscle cells with a brown chromogen. Reprinted with permission from Moreno PR, et al. Circulation 2004;110:2032–8.
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Figure 7 Error bars showing the mean (95% confidence interval) of microvessel content in non-disrupted and disrupted human atherosclerotic plaques. Comparisons of microvessel content within plaque/shoulder, tunica media, medial, plaque base, and total neovessel numbers between non-ruptured and ruptured plaques are presented.
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Figure 8 Direct and indirect effects of peroxisomal proliferator-activated receptors (PPARs). Peroxisomal proliferator-activated receptor activation by synthetic ligands induces metabolic changes that may limit inflammation and atherosclerosis indirectly. Alternatively, the expression of PPARs in most major vascular and inflammatory cells and PPAR regulation of relevant target genes in those cells raises the possibility that PPARs have a direct effect on inflammation and atherosclerosis. ABCA1 = ATP-binding cassette transporter 1; HDL = high-density lipoprotein; IFN = interferon gamma; MCP1 = monocyte chemoattractive protein-1; VCAM1 = vascular cell adhesion molecule-1. Reprinted with permission from Plutzky (67).
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