Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151814 (coronary occlusion)
 3,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We support the concept of a common anatomic and physiologic link between the acute coronary syndromes, which consists of plaque fissuring or rupture, leading to exposure of the circulating blood to collagen, lipids, and smooth muscle cells. This, in turn, results in marked platelet activation and the initiation of the coagulation sequence, both of which lead to thrombus formation. What determines the clinical outcome in these patients is the suddenness of coronary occlusion, the completeness of blood flow deprivation, and most importantly, its duration. In unstable angina, either plaque disruption resulting in an abrupt change in its morphologic configuration with reduction of coronary blood flow or increased myocardial oxygen demand are associated with increased exertional symptoms. In rest angina, two events may take place: formation of a transient and labile thrombus due to platelet and clotting activation, or vasospasm associated with the release of platelet-derived vasoconstrictive substances or loss of endothelial relaxing properties. As a result, transient myocardial ischemia occurs, which may be intermittent and recurrent and may progress to myocardial infarction or sudden death. In myocardial infarction, plaque rupture is usually more severe, leading to the formation of an occlusive or near-occlusive thrombus which may be more persistent and fixed to the arterial wall. The duration of coronary blood flow deprivation needs to be sufficiently long in order to produce myocardial cell death. Moreover, the difference between Q-wave and non-Q-wave infarction is probably determined by the duration of blood flow obstruction, being longer in the former. The presence of a functionally adequate collateral circulation will, in part, determine the survival of the area of myocardium at jeopardy. The coronary events that take place in ischemic sudden death are probably similar to those in unstable angina, namely plaque rupture with thrombus formation. In sudden death, the resulting myocardial ischemia may precipitate fatal ventricular arrhythmias. Alternatively, platelet microemboli from ulcerated arterial plaques may produce multiple areas of myocardial necrosis which can result in electrical instability and ventricular fibrillation.
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PMID:Thrombosis/platelets and other blood factors in acute coronary syndromes. 265 27

Platelets are suggested to exacerbate ischemia-induced myocardial injury, which has led to the study of various antiplatelet therapies including thromboxane synthetase inhibitors (TXSI). Two such agents, benzylimidazole and OKY-046, reduce infarct size commensurate with a diminution in serum thromboxane B2 formation in anesthetized dogs subjected to 90 minutes of coronary artery occlusion followed by 5 hours of reperfusion. In contrast, platelet depletion with specific antiserum does not reduce infarct size but prevents the cardioprotection afforded by the TXSI. Platelet-derived prostaglandin endoperoxides (PGG2 and PGH2), which cannot be converted to thromboxane A2 in the inhibited platelet, can be transformed to PGE2 and PGD2 in plasma and to PGI2 by the blood vessel wall. These prostaglandins are considered "cardioprotective." Consequently, a low dose of aspirin (3-5 mg/kg) given 24 hours before coronary occlusion was used to selectively block the platelet cyclooxygenase enzyme. Aspirin, by itself, does not reduce infarct size, but it suppresses the myocardial salvage induced by OKY-046. Thus, TXSI reduce infarct size by platelet-dependent, aspirin-sensitive mechanism that depends on the redirection of platelet-derived PGG2 and PGH2 to protective metabolites, rather than inhibition of thromboxane A2 per se. Moreover, myocardial salvage induced by the TXSI is accompanied by a reduction in neutrophil accumulation in the myocardium, as indicated by the levels of the neutrophil-specific myeloperoxidase enzyme. Platelet depletion or pretreatment with aspirin prevents the TXSI-induced suppression of neutrophil accumulation. Consequently, it is proposed that the prostaglandin-mediated protective effects of TXSI can be resolved, at least in part, in terms of a braking action on neutrophil activation to prevent leukocyte-dependent tissue injury.
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PMID:Thromboxane synthetase inhibitors reduce infarct size by a platelet-dependent, aspirin-sensitive mechanism. 312 73

Platelets become activated during myocardial infarction (MI), but the direct contribution of activated platelets to myocardial reperfusion injury in vivo has yet to be reported. We tested the hypothesis that activated platelets contribute importantly to reperfusion injury during MI in mice. After 30 min of ischemia and 60 min of reperfusion, P-selectin knockout mice had a significantly smaller infarct size than that of wild-type mice (P < 0.05). Platelets were detected by P-selectin antibody in the previously ischemic region of wild-type mice as early as 2 min postreperfusion after 45 min, but not 20 min, of ischemia. The appearance of neutrophils in the heart was delayed when compared with platelets. Flow cytometry showed that the number of activated platelets more than doubled after 45 min of ischemia when compared with 20 min of ischemia or sham treatment (P < 0.05). Platelet-rich or platelet-poor plasma was then transfused from either sham-operated or infarcted mice after 45 and 10 min of ischemia-reperfusion to mice undergoing 20 and 60 min of ischemia-reperfusion. Infarct size was increased by threefold and platelet accumulation was remarkably enhanced in mice treated with wild-type, MI-activated platelet-rich plasma but not in mice receiving either platelet-poor plasma from wild types or MI-activated platelet-rich plasma from P-selectin knockout mice. In conclusion, circulating platelets become activated early during reperfusion and their activation depends on the duration of the preceding coronary occlusion and is proportional to the extent of myocardial injury. Activated platelets play an important role in the process of myocardial ischemia-reperfusion injury, and platelet-derived P-selectin is a critical mediator.
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PMID:Activated platelets contribute importantly to myocardial reperfusion injury. 1619 80

Cardiovascular disease--a leading cause of morbidity and mortality among adults-is strongly influenced by platelet function through acute thrombotic and atherogenic mechanisms. Pathways that regulate platelet activity and lead to coronary occlusion are central to the pathogenesis of acute coronary syndromes. Platelet activation contributes to other thrombotic disorders and cardiovascular diseases, including stroke. Anucleate platelets are now understood to contain transcripts that might relate to other physiological or pathophysiological conditions, be released into the circulation, participate in protein formation, and engage in horizontal RNA transfer to other vascular cells. These platelet transcripts include microRNAs (miRNAs), which are small noncoding RNAs involved in many molecular processes, most notably regulation of gene expression. In platelets, these noncoding RNAs seem to participate in vascular homeostasis, inflammation, and platelet function. In addition, levels of platelet miRNAs in the circulation are associated with the presence or extent of cardiovascular diseases, such as atrial fibrillation and peripheral vascular disease. Accumulating data suggest mechanistic roles for platelet-derived miRNAs in haemostasis, thrombosis, and unstable coronary syndromes. In addition, evidence suggests that platelet-derived miRNAs might have important roles as biomarkers of cardiovascular disease susceptibility, prognosis, or treatment.
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PMID:MicroRNAs in platelet function and cardiovascular disease. 2614 83