Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulating evidence points towards a role for proteases and protease inhibitors in tissue remodelling and repair in a variety of organs. In particular-besides the matrix metalloprotease system-the plasminogen activator (PA)/plasmin system has been implicated in these processes in the heart. Urokinase type PA (u-PA) and PA inhibitor type 1 (PAI-1) seem to modulate cardiac rupture and infarct healing. In this study we aimed to investigate whether inflammatory mediators can regulate the expression of components of the PA/plasmin system in human adult cardiac myocytes (HACM). We could demonstrate that HACM, isolated from pieces of myocardial tissue by mechanical dispersion and characterized by positive immunostaining for the cardiac markers troponin I, tropomyosin, cardiotin and myocardial muscle-actin, in vitro express PAI-1 and tissue type PA (t-PA) whereas u-PA was not detectable in these cells. PAI-1 protein production was increased up to twofold by interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) and up to fivefold by transforming growth factor-beta (TGF-beta) and oncostatin M (OSM). Similar changes were observed in PAI-1 transcript levels after cytokine treatment. t-PA production in HACM was not affected by these agonists. No effect of these cytokines on PAI-1 production in fibroblasts isolated from human myocardial tissue was seen. In an ex vivo model we could show that incubation of pieces of human myocardial tissue with these cytokines also resulted in an increase in PAI-1 in cardiac myocytes as evidenced by immuno-histochemistry. Furthermore we found increased PAI-1 expression in myocardial tissue from a patient suffering from acute myocarditis. Thus for the first time we provide evidence that inflammatory mediators modulate PAI-1 expression in human adult cardiac myocytes in vitro and ex vivo and could demonstrate that PAI-1 expression is increased in the in vivo setting under inflammatory conditions. If the effect on PAI-1 expression brought about by IL-1alpha, TNF-alpha, TGF-beta and OSM is not only operative under in vitro and ex vivo conditions but also in the in vivo setting one could speculate that these cytokines contribute to upregulation of PAI-1 in myocardial tissue and that PAI-1, when upregulated in myocardial tissue during inflammatory processes, could serve as a defence mechanism against excessive matrix degradation by proteases. Thus we propose a role for PAI-1 produced in the heart by cardiac myocytes in cardiac remodelling and repair processes.
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PMID:Plasminogen activator inhibitor 1 expression is regulated by the inflammatory mediators interleukin-1alpha, tumor necrosis factor-alpha, transforming growth factor-beta and oncostatin M in human cardiac myocytes. 1250 65

A 38-year-old cocaine abuser was admitted to the Emergency Department with a one hour history of precordial chest pain associated with shortness of breath and extreme discomfort. On admission his blood pressure was 90/60 mmHg, the resting 12-lead ECG showed ventricular tachycardia at about 300 beats per minute, and oxygen saturation was 86 percent in room air. After electrical cardioversion, the 12-lead ECG revealed sinusal rhythm and a significative ST segment elevation in leads I, aVL and V1-V6, that was about 0.5 mV in leads I and aVL and more than 1 mV in leads V2, V3 and V4. Laboratory determinations showed elevated creatine-chinase MB (CK-MB) and troponin I. An emergency coronary angiogram was normal. Cocaine use is a major cause of acute myocardial infarction in patients with normal epicardial coronary arteries but the exact mechanism still remains unclear. We hypothesize a non-IgE mediated mast-cell activation, with a direct action played by cocaine, and consequent massive expression of several factors effecting the microcirculatory system, including pro-inflammatory cytokines and chemokines. Our hypothesis is supported by an elevated serum tryptase levels in the patient.
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PMID:High serum tryptase value in massive acute myocardial infarction with ventricular arrhythmia exortion in a cocaine abuser. 1950 5

Kounis syndrome (KS) is characterized by concurrent acute coronary syndrome and allergic reaction, in which acute inflammatory mediators cause spasm and/or erosion and rupture of coronary atheromatous plaque. In this report, we remind clinicians to consider KS in patients who are subjected to allergenic substances and demonstrate acute chest pain. A 36-year-old woman had chest pain, severe dyspnea, hypotension, and symmetrical negative T waves on the anterior leads during electrocardiography approximately two hours after the use of clarithromycin. KS was considered as a possible diagnosis based on the presentation. Laboratory tests revealed an elevated level of troponin I, suggesting myocardial infarction, and an elevated level of serum tryptase level, suggesting an allergic reaction. The patient promptly underwent coronary angiography, which revealed only plaques in all main coronary arteries without any obstructive lesion. To the best of our knowledge, we report herein the first case in the literature describing an association between clarithromycin and KS.
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PMID:Acute coronary syndrome secondary to clarithromycin: the first case and review of the literature. 2508 Sep 53