Inhibition of type 2A secretory phospholipase A2 reduces death of cardiomyocytes in acute myocardial infarction
| Autor: | Richard Berney, Marieke D. Spreeuwenberg, C. Erik Hack, Paul A.J. Krijnen, Florine J. van Milligen, Annemieke van Dijk, Amanda Pronk, Hans W.M. Niessen, Rob A. Vermond, Frans C. Visser, Walter Paulus |
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| Přispěvatelé: | Pathology, Surgery, Epidemiology and Data Science, Cardiology, Physiology, Clinical chemistry, ICaR - Heartfailure and pulmonary arterial hypertension |
| Rok vydání: | 2009 |
| Předmět: |
Simvastatin
Cancer Research medicine.medical_specialty Neutrophils Clinical Biochemistry Myocardial Infarction Ischemia Pharmaceutical Science Apoptosis Inflammation Pharmacology Group II Phospholipases A2 Cell Movement In vivo medicine Animals Myocyte Myocytes Cardiac Myocardial infarction Enzyme Inhibitors Rats Wistar Biochemistry medical Caspase 3 business.industry Macrophages Cell Membrane Biochemistry (medical) Cell Biology medicine.disease Immunohistochemistry In vitro Rats Surgery Disease Models Animal Solubility Heart Function Tests medicine.symptom Wound healing business |
| Zdroj: | van Dijk, A, Krijnen, P A J, Vermond, R A, Pronk, A C B, Spreeuwenberg, M D, Visser, F C, Berney, R, Paulus, W J, Hack, C E, van Milligen-Kummer, F J & Niessen, J W M 2009, ' Inhibition of type 2A secretory phospholipase A(2) reduces death of cardiomyocytes in acute myocardial infarction ', Apoptosis, vol. 14, no. 6, pp. 753-763 . https://doi.org/10.1007/s10495-009-0350-x Apoptosis, 14(6), 753-763. Springer Netherlands |
| ISSN: | 1573-675X 1360-8185 |
| DOI: | 10.1007/s10495-009-0350-x |
| Popis: | During acute myocardial infarction (AMI), ischemia leads to necrotic areas surrounded by border zones of reversibly damaged cardiomyocytes, showing membrane flip-flop. During reperfusion type IIA secretory phopholipase A(2) (sPLA(2)-IIA) induces direct cell-toxicity and facilitates binding of other inflammatory mediators on these cardiomyocytes. Therefore, we hypothesized that the specific sPLA(2)-IIA-inhibitor PX-18 would reduce cardiomyocyte death and infarct size in vivo. Wistar rats were treated with PX-18 starting minutes after reperfusion, and at day 1 and 2 post AMI. After 28 days hearts were analyzed. Furthermore, the effect of PX-18 on membrane flip-flop and apoptosis was investigated in vitro. PX-18 significantly inhibited sPLA(2)-IIA activity and reduced infarct size (reduction 73 +/- 9%, P0.05), compared to the vehicle-treated group, without impairing wound healing. In vitro, PX-18 significantly reduced reversible membrane flip-flop and apoptosis in cardiomyocytes. However, no sPLA(2)-IIA activity could be detected, suggesting that PX-18 also exerted a protective effect independent of sPLA(2)-IIA. In conclusion, PX-18 is a potent therapeutic to reduce infarct size by inhibiting sPLA(2)-IIA, and possibly also by inhibiting apoptosis of cardiomyocytes in a sPLA(2)-IIA independent manner. |
| Databáze: | OpenAIRE |
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