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.

Atherothrombosis: role of tissue factor; link between diabetes, obesity and inflammation.

Atherothrombotic vascular disease is a complex disorder in which inflammation and coagulation play a pivotal role. Rupture of high-risk, vulnerable plaques with the subsequent tissue factor (TF) exposure is responsible for coronary thrombosis, the main cause of unstable angina, acute myocardial infarction, and sudden cardiac death. Tissue factor (TF), the key initiator of coagulation is an important modulator of inflammation. TF is widely expressed in atherosclerotic plaques and found in macrophages, smooth muscle cells, extracellular matrix and acellular lipid-rich core. TF expression can be induced by various stimulants such as C-reactive protein, oxLDL, hyperglycemia and adipocytokines. The blood-born TF encrypted on the circulating microparticles derived from vascular cells is a marker of vascular injury and a source of procoagulant activity. Another form of TF, called alternatively spliced has been recently identified in human and murine. It is soluble, circulates in plasma and initiates coagulation and thrombus propagation. Evidence indicates that elevated levels of blood-borne or circulating TF has been associated with metabolic syndrome, type 2 diabetes and cardiovascular risk factors and is a candidate biomarker for future cardiovascular events. Therapeutic strategies have been developed to specifically interfere with TF activity in the treatment of cardiovascular disease.