Byline: Gundu. Rao
The role of blood components including platelets, in initiating inflammation, endothelial dysfunction, atherosclerosis, thrombus formation, thrombus growth, and acute vascular ischemic events, is well established. Given this recognized role played by platelets, there is a considerable interest in understanding the physiology and function of platelets, as well as in the development of novel platelet function-inhibitory drugs. The generation of the second messengers, calcium mobilization, shape change, adhesion, aggregation, contraction, release of granule contents, thrombus development, thrombus growth, and formation of hemostatic plug at the injured vessel surfaces, in brief, constitute platelet activation. Some of the known compounds that inhibit platelet activation include inhibitors of arachidonic metabolism (cyclooxygenase-1 inhibitors; aspirin, ibuprofen, etc.), adenosine diphosphate receptor antagonists (P2Y [sub]12 inhibitors), adenylyl and guanylyl cyclase stimulators, calcium antagonists, and GP11b/111a receptor antagonists. Since platelets have multiple mechanisms of achieving in vivo activation, it is difficult to design a novel drug that offers total protection for developing acute ischemic vascular events, without compromising coagulation mechanisms. Given this complexity, any aggressive antiplatelet therapy results in increased bleeding episodes. Having said that, we feel that there is a great window of opportunity for developing novel antiplatelet therapies. There is also scope for the development of fixed-dose combinations for the primary and secondary management of chronic diseases such as hypertension, heart disease, and type-2 diabetes.
Atherosclerosis is a chronic, complex, inflammatory disease of the blood vessels, which leads to the narrowing and hardening of the arteries.  Thrombosis is another associated multifactorial disease that causes reduction and blockage of the flow of blood to the tissues, causing ischemia and tissue injury. Together, these vascular diseases leading to heart attacks and stroke are the leading causes of morbidity and mortality worldwide. , A variety of risk factors contribute to the pathogenesis of these diseases. Some of the well-known risk factors include smoking, inflammation, endothelial dysfunction, hypertension, diabetes, repeated injury of the vascular tissues, elevated levels of low-density lipoproteins, low levels of high-density lipoproteins (HDL), visceral adiposity, and sedentary lifestyle. Some of the newer emerging risk factors include increased levels of fibrinogen, elevation of circulating activating factor, circulating endothelial cells, increased stress, depression, decreased levels of Vitamin B [sub]12 , Vitamin D, elevated blood phosphorous, C-reactive protein, platelet microparticles, platelet hyperfunction, and hypercoagulability. Since the time Framingham trials listed the predictors of risk (http://www.framinghamheartstudy.org/risk) (age, diabetes, smoking, systolic blood pressure (BP), total cholesterol, HDL cholesterol, and body mass index) for acute vascular events, there has been a great interest in reducing modifiable risks with appropriate intervention. In spite of decades of research in this field, the role of platelets in the initiation of inflammation, vascular dysfunction, atherosclerosis, ischemic heart disease, and stoke is not very well defined. In this overview, an attempt is made to provide some evidence to support the hypothesis that platelets play a very significant role in the promotion of events leading to acute coronary and cerebrovascular events. ,,,,,,,,,,,,,,,,, Unlike other reviews on the subject, no attempt will be made to catalog...