September 9, 2026Journal of the American College of Cardiology337 citationsOpen Access
New aspects in the pathogenesis of diabetic atherothrombosis
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Key Result
Diabetic atherothrombosis pathogenesis involves inflammation, oxidative stress, and tissue factor, with HDL therapy and PPAR-gamma agonists showing promise for plaque stabilization.
Key Points
- To examine the cellular and molecular mechanisms underlying accelerated plaque formation and clot development in diabetes.
- Synthesized biological and clinical evidence exploring vascular endothelium changes, platelet hyperactivity, and coagulation cascades in diabetic states.
- Reviewed the pathological roles of sustained hyperglycemia, insulin resistance, and oxidative stress in arterial disease.
- Hyperglycemia and insulin resistance drive endothelial dysfunction, increase oxidative stress, and destabilize arterial atherosclerotic plaques.
- Platelet hyperreactivity and altered fibrin clot structures significantly elevate arterial thrombosis risk in diabetic patients.
Structured PICO
P
Population
Patients with diabetes mellitus and experimental models of diabetic atherosclerosis
This review summarizes the complex interplay of inflammation, hyperglycemia, and oxidative stress in diabetic atherothrombosis, highlighting emerging therapies like HDL and PPAR-gamma agonists.
Abstract
Diabetes mellitus is increasing worldwide, resulting from the interaction of obesity, inflammation, and hyperglycemia. Activated immunity and cytokine production lead to insulin resistance and other components of the metabolic syndrome, establishing the link between diabetes and atherosclerosis. Hyperglycemia-induced endothelial dysfunction is mediated by increased oxidative stress, a promoter of adventitial inflammation and vasa vasorum neovascularization in experimental models of diabetic atherosclerosis. Recent studies have documented increased inflammation, neovascularization, and intraplaque hemorrhage in human diabetic atherosclerosis. This inflammatory microangiopathic process is independently associated with plaque rupture, leading to coronary thrombosis. Tissue factor, the most potent trigger of the coagulation cascade, is increased in diabetic patients with poor glycemic control. Circulating tissue factor microparticles are also associated with apoptosis of plaque macrophages, closing the link among inflammation, plaque rupture, and blood thrombogenicity. High-density lipoproteins, responsible for free cholesterol removal, are reduced in patients with insulin resistance and diabetes. High-density lipoprotein therapy leads to a significant decrease in plaque macrophages and increase in smooth-muscle cells. These beneficial effects may be responsible for coronary plaque stabilization in patients treated with recombinant Apolipoprotein A-I Milano/phospholipid complex. Finally, peroxisomal proliferator-activated receptors (PPARs) are now considered the nuclear transcriptional regulators of atherosclerosis. Three subfamilies, including PPAR-alpha, -delta, and -gamma, have been identified with crucial roles in lipid metabolism, plaque inflammation, expression of adhesion molecules and cytokines, and regulation of matrix metalloproteinases. Multiple experimental studies have documented plaque stabilization with PPAR-gamma agonists, a group of medications holding great promise in the treatment of diabetes atherosclerosis.
Cite This Study
Moreno et al. (2004) conducted a review in Diabetic atherothrombosis. Diabetic atherothrombosis pathogenesis involves inflammation, oxidative stress, and tissue factor, with HDL therapy and PPAR-gamma agonists showing promise for plaque stabilization.