التفاصيل البيبلوغرافية
| العنوان: |
Lysophosphatidic acid acts on LPA1 receptor to increase H2 O2 during flow-induced dilation in human adipose arterioles. |
| المؤلفون: |
Chabowski, Dawid S, Kadlec, Andrew O, Ait‐Aissa, Karima, Hockenberry, Joseph C, Pearson, Paul J, Beyer, Andreas M, Gutterman, David D, Ait-Aissa, Karima |
| المصدر: |
British Journal of Pharmacology; Nov2018, Vol. 175 Issue 22, p4266-4280, 15p, 2 Charts, 6 Graphs |
| مصطلحات موضوعية: |
LYSOPHOSPHOLIPIDS, LYSOPHOSPHATIDIC acid receptors, HYDROGEN peroxide, ADIPOSE tissues, CORONARY disease, ANALYSIS of hydrogen peroxide, ARTERIES, CELL culture, CELL receptors, COMPARATIVE studies, RESEARCH methodology, MEDICAL cooperation, MITOCHONDRIA, PHOSPHOLIPIDS, PATHOLOGICAL physiology, RESEARCH, RESEARCH funding, EVALUATION research |
| مستخلص: |
Background and Purpose: NO produces arteriolar flow-induced dilation (FID) in healthy subjects but is replaced by mitochondria-derived hydrogen peroxide (mtH2 O2 ) in patients with coronary artery disease (CAD). Lysophosphatidic acid (LPA) is elevated in patients with risk factors for CAD, but its functional effect in arterioles is unknown. We tested whether elevated LPA changes the mediator of FID from NO to mtH2 O2 in human visceral and subcutaneous adipose arterioles.Experimental Approach: Arterioles were cannulated on glass micropipettes and pressurized to 60 mmHg. We recorded lumen diameter after graded increases in flow in the presence of either NOS inhibition (L-NAME) or H2 O2 scavenging (Peg-Cat) ± LPA (10 μM, 30 min), ±LPA1 /LPA3 receptor antagonist (Ki16425) or LPA2 receptor antagonist (H2L5186303). We analysed LPA receptor RNA and protein levels in human arterioles and human cultured endothelial cells.Key Results: FID was inhibited by L-NAME but not Peg-Cat in untreated vessels. In vessels treated with LPA, FID was of similar magnitude but inhibited by Peg-Cat while L-NAME had no effect. Rotenone attenuated FID in vessels treated with LPA indicating mitochondria as a source of ROS. RNA transcripts from LPA1 and LPA2 but not LPA3 receptors were detected in arterioles. LPA1 but not LPA3 receptor protein was detected by Western blot. Pretreatment of vessels with an LPA1 /LPA3 , but not LPA2 , receptor antagonist prior to LPA preserved NO-mediated dilation.Conclusions and Implications: These findings suggest an LPA1 receptor-dependent pathway by which LPA increases arteriolar release of mtH2 O2 as a mediator of FMD. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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