Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report describes studies on the activation of coagulation factor VII (FVII) and the inhibition of the extrinsic coagulation pathway in acute ischaemic heart disease. FVII and the inhibitor of the tissue thromboplastin-FVII complex, called extrinsic pathway inhibitor (EPI), were determined in plasma from 68 patients and compared to findings in 37 normal individuals. The mean FVII amidolytic activity, the mean FVII clotting activity, as well as the FVII clotting/FVII amidolytic ratio were not significantly different in the patient groups as compared to the controls. The fraction of FVII clotting activity that is sensitive to phospholipase C, 'the FVII-phospholipid complex', was 8% in controls, 19% (P less than 0.05) in patients with acute myocardial infarction, 15% (n.s.) in angina pectoris and 13% (n.s.) in heart failure/arrhythmia patients. The 'FVII-phospholipid complex' was highly significantly correlated to triglycerides in plasma in patients with acute myocardial infarction (r = 0.88, P less than 0.001) and angina pectoris (r = 0.89, P less than 0.001). The mean EPI levels were significantly increased in patients with acute myocardial infarction (132%), angina pectoris (134%), and heart failure (150%) as compared to the control population (110%). The FVII clotting/EPI ratio was significantly decreased both in patients with acute myocardial infarction and heart failure, whereas the FVII amidolytic/EPI ratio was significantly decreased only in the heart failure group. Apparently, in patients with acute ischaemic heart disease, a moderate increase in the procoagulant activity is accompanied by a marked increase in the anticoagulant activity of the extrinsic coagulation pathway, suggesting a balanced activation system.
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PMID:Factor VII and extrinsic pathway inhibitor in acute coronary disease. 278 54

Endothelin-1 (ET-1) induces severe pathologic conditions such as coronary spasm followed by vasospastic angina pectoris and acute myocardial infarction. The related pathophysiologic mechanisms have remained obscure. Endothelin-1 receptor (ET(A) and ET(B)) is reported to couple with several types of G protein-involved pathways that participate in phospholipase C activation and atrial myofibrils organization into sarcomeric units. Here we demonstrate that ET-1 induces histologic and pathologic dysfunction in the rabbit myocardium and that such pathologic events are prevented by the Rho-kinase inhibitor fasudil. Although the bolus injection of ET-1 (1.4 nmol/kg) via the auricular vein of the rabbit induced only transient T-wave elevation, irreversible, severe histologic changes were observed in papillary muscles of the ventricle, and multifocal myocardial necrosis with infiltration of neutrophils and macrophages in the left ventricle occurred. Oral administration of fasudil (10 mg/kg) significantly reduced the occurrence of myocardial injury determinants, whereas conventional Ca2+ channel blockers (nifedipine, diltiazem) and a K+ channel opener (nicorandil; 10 mg/kg, p.o. each) showed a lesser or no effect on such determinants. These results suggest that ET-1 induces severe myocardial dysfunction based not only on the occurrence of vasospastic ischemia but also on its direct effects on the myocardium.
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PMID:The protein kinase inhibitor fasudil protects against ischemic myocardial injury induced by endothelin-1 in the rabbit. 1067 51

Leukocyte-released antimicrobial peptides contribute to pathogen elimination and activation of the immune system. Their role in thrombosis is incompletely understood. Here we show that the cathelicidin LL-37 is abundant in thrombi from patients with acute myocardial infarction. Its mouse homologue, CRAMP, is present in mouse arterial thrombi following vascular injury, and derives mainly from circulating neutrophils. Absence of hematopoietic CRAMP in bone marrow chimeric mice reduces platelet recruitment and thrombus formation. Both LL-37 and CRAMP induce platelet activation in vitro by involving glycoprotein VI receptor with downstream signaling through protein tyrosine kinases Src/Syk and phospholipase C. In addition to acute thrombosis, LL-37/CRAMP-dependent platelet activation fosters platelet-neutrophil interactions in other inflammatory conditions by modulating the recruitment and extravasation of neutrophils into tissues. Absence of CRAMP abrogates acid-induced lung injury, a mouse pneumonia model that is dependent on platelet-neutrophil interactions. We suggest that LL-37/CRAMP represents an important mediator of platelet activation and thrombo-inflammation.
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PMID:Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation. 2967 76