| Autor: |
Ilona Kareinen, Marc Baumann, Su Duy Nguyen, Katariina Maaninka, Andrey Anisimov, Minoru Tozuka, Matti Jauhiainen, Miriam Lee-Rueckert, Petri T. Kovanen |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| Zdroj: |
Journal of Lipid Research, Vol 59, Iss 6, Pp 945-957 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
0022-2275 |
| DOI: |
10.1194/jlr.M077503 |
| Popis: |
ApoA-I, the main structural and functional protein of HDL particles, is cardioprotective, but also highly sensitive to proteolytic cleavage. Here, we investigated the effect of cardiac mast cell activation and ensuing chymase secretion on apoA-I degradation using isolated rat hearts in the Langendorff perfusion system. Cardiac mast cells were activated by injection of compound 48/80 into the coronary circulation or by low-flow myocardial ischemia, after which lipid-free apoA-I was injected and collected in the coronary effluent for cleavage analysis. Mast cell activation by 48/80 resulted in apoA-I cleavage at sites Tyr192 and Phe229, but hypoxic activation at Tyr192 only. In vitro, the proteolytic end-product of apoA-I with either rat or human chymase was the Tyr192-truncated fragment. This fragment, when compared with intact apoA-I, showed reduced ability to promote migration of cultured human coronary artery endothelial cells in a wound-healing assay. We propose that C-terminal truncation of apoA-I by chymase released from cardiac mast cells during ischemia impairs the ability of apoA-I to heal damaged endothelium in the ischemic myocardium. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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