phospholipase A(2)
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- MeSH
- fosfolipasy A farmakologie chemie MeSH
- fosfolipidy metabolismus MeSH
- hydrolýza MeSH
- kyselina arachidonová metabolismus MeSH
- membrány MeSH
- Publikační typ
- přehledy MeSH
Cardiac resistance against acute ischemia/reperfusion (I/R) injury can be enhanced by adaptation to chronic intermittent hypoxia (CIH), but the changes at the molecular level associated with this adaptation are still not fully explored. Phospholipase A2 (PLA2) plays an important role in phospholipid metabolism and may contribute to membrane destruction under conditions of energy deprivation during I/R. The aim of this study was to determine the effect of CIH (7000 m, 8 h/day, 5 weeks) on the expression of cytosolic PLA2α (cPLA2α) and its phosphorylated form (p-cPLA2α), as well as other related signaling proteins in the left ventricular myocardium of adult male Wistar rats. Adaptation to CIH increased the total content of cPLA2α by 14 % in myocardial homogenate, and enhanced the association of p-cPLA2α with the nuclear membrane by 85 %. The total number of β-adrenoceptors (β-ARs) did not change but the β2/β1 ratio markedly increased due to the elevation of β2-ARs and drop in β1-ARs. In parallel, the amount of adenylyl cyclase decreased by 49 % and Giα proteins increased by about 50 %. Besides that, cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2) increased by 36 and 84 %, respectively. In parallel, we detected increased phosphorylation of protein kinase Cα, ERK1/2 and p38 (by 12, 48 and 19 %, respectively). These data suggest that adaptive changes induced in the myocardium by CIH may include activation of cPLA2α and COX-2 via β2-AR/Gi-mediated stimulation of the ERK/p38 pathway.
- MeSH
- beta-2-adrenergní receptory metabolismus MeSH
- chronická nemoc MeSH
- cyklooxygenasa 2 metabolismus MeSH
- fosfolipasy A2, skupina IV metabolismus MeSH
- ischemická choroba srdeční metabolismus patologie MeSH
- krysa rodu rattus MeSH
- MAP kinasový signální systém * MeSH
- mitogenem aktivované proteinkinasy p38 metabolismus MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
American journal of cardiology, ISSN 0002-9149 vol. 101, no. 12, suppl. 12A, June 16, 2008
57 s. : il., tab. ; 28 cm
- MeSH
- 1-alkyl-2-acetylglycerofosfocholinesterasa MeSH
- fosfolipasy A2 MeSH
- koronární nemoc MeSH
- rizikové faktory MeSH
- ruptura aorty MeSH
- Publikační typ
- sborníky MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- kardiologie
Selective inhibitors of secretory phospholipase A2 and lipoprotein-associated phospholipase A2 are potential candidates for reducing recurrent cardiovascular events in patients with established coronary heart disease (CHD). With the active enrollment of CHD patients into phase III clinical trials with both classes of inhibitors, this article reviews the available experimental animal and human trial evidence that provides the rationale for the development of the phospholipase A2 inhibitors varespladib methyl and darapladib as preventive therapy. RECENT FINDINGS: Recently completed experimental animal studies, human biomarker data, and vascular imaging studies provide support for proceeding with clinical outcome trials secretory phospholipase A2 and lipoprotein-associated phospholipase A2 inhibition. SUMMARY: Both secretory phospholipase A2 and lipoprotein-associated phospholipase A2 inhibitors hold promise for the reduction of recurrent cardiovascular events in patients treated with current standards of care. The completion of the ongoing clinical event trials has the potential to provide a new dimension to secondary preventive therapy.
- MeSH
- 1-alkyl-2-acetylglycerofosfocholinesterasa antagonisté a inhibitory MeSH
- acetáty aplikace a dávkování terapeutické užití MeSH
- ateroskleróza enzymologie epidemiologie farmakoterapie patofyziologie MeSH
- benzaldehydy aplikace a dávkování terapeutické užití MeSH
- biologické markery analýza MeSH
- cílená molekulární terapie metody MeSH
- indoly aplikace a dávkování terapeutické užití MeSH
- klinické zkoušky kontrolované jako téma MeSH
- lékové formy MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši transgenní MeSH
- myši MeSH
- oximy aplikace a dávkování terapeutické užití MeSH
- rizikové faktory MeSH
- sekreční fosfolipasy A2 antagonisté a inhibitory MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
OBJECTIVE. Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is extensively expressed by advanced atherosclerotic lesions and may play a role in plaque instability. We selected a group of elderly subjects that underwent transcatheter aortic valve implantation (TAVI) or balloon angioplasty (BA) and separated them into two groups, diabetic and nondiabetic, to compare the level of Lp-PLA₂ mass between them. METHODS. 44 patients aged 79.6 ± 5.6 years with symptomatic severe aortic valve stenosis underwent TAVI (n = 35) or BA (n = 9). 21 subjects had confirmed type 2 diabetes mellitus. Lp-PLA₂ mass was measured using an enzyme-linked immunosorbent assay kit (USCN Life Science, China) before and 3 days after the procedure. RESULTS. Lp-PLA₂ mass was significantly elevated in this population (1296 ± 358 ng/mL before TAVI; 1413 ± 268 ng/mL before BA) and further increased after TAVI (1604 ± 437 ng/mL, P < 0.01) or BA (1808 ± 303 ng/mL, P < 0.01). Lp-PLA₂ mass was significantly increased on the diabetic group before these interventions. CONCLUSION. Lp-PLA₂ may be a novel biomarker for the presence of rupture-prone atherosclerotic lesions in elderly patients. Levels of Lp-PLA₂ in diabetic patients may accompany the higher amount of small dense LDL particles seen in these subjects.
- MeSH
- 1-alkyl-2-acetylglycerofosfocholinesterasa krev MeSH
- aortální chlopeň chirurgie MeSH
- aortální stenóza komplikace chirurgie terapie MeSH
- aterosklerotický plát etiologie MeSH
- ateroskleróza krev komplikace enzymologie patofyziologie MeSH
- balónková angioplastika škodlivé účinky MeSH
- biologické markery krev MeSH
- chirurgická náhrada chlopně škodlivé účinky MeSH
- diabetes mellitus 2. typu komplikace MeSH
- diabetické angiopatie krev enzymologie patofyziologie MeSH
- lidé MeSH
- následné studie MeSH
- průřezové studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stárnutí * MeSH
- stupeň závažnosti nemoci MeSH
- upregulace * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
