Platelet hyperfunction as risk factor for chronic and acute coronary events

Indians have a very high incidence of vascular complications, such as hypertension, atherosclerosis, coronary artery disease (CAD), and stroke, compared to any other ethnic group in the world. They also have a very high incidence of multiple metabolic diseases, including type 2 diabetes. Elevated levels of known risk factors in this population for CAD does not explain adequately the significant increase in the vascular disease burden in this population. There is some speculation that genetic predisposal of this population may account for this increased incidence in vascular diseases. Environmental toxicants may also contribute significantly to the acceleration of these complex risk promoters. Functional and structural changes in the arterial wall precede the development of clinical complications such as endothelial dysfunction, hypertension, atherosclerosis, hyperfunction of platelets, and coagulation cascade. Vascular dysfunction, therefore, is the major contributor for the pathogenesis of hypertension, atherogenesis, thrombosis, and stroke. Alterations in the balance between platelet-associated vasoconstrictors and endothelial-derived vasodilators result in the vascular dysfunction. Blood platelets play a very important role in the pathogenesis of hypertension, atherogenesis, thrombosis, and stroke. These cells interact with a variety of agonists. Such interactions stimulate specific receptors and lead to the activation of intracellular effector enzymes. Ionized calcium is the primary bioregulator and a variety of signaling mechanisms modulate the cellular physiology and functions. Activated platelets promote the formation of thrombin and initiate coagulation cascade. They also interact with other circulating blood cells and facilitate inflammatory response. Little is known about the effect of environmental toxicants on vascular physiology and pathology. This is true also on their effect on the circulating blood cells. There is some evidence that oxidative stress as well as proinflammatory compounds play a role in vascular biology. In this presentation an attempt will be made to briefly review the known risk factors for CAD; the role of toxicants, eicosanoids, and inflammatory mediators on vascular biology specifically; and the role of platelets and platelet-derived biomolecules on hypertension, atherogenesis, thrombosis, and intercellular communications. Alterations in signaling pathways by environmental toxicants may increase the risk for hypertension, atherosclerosis, thrombosis, and stroke.