Finosh G Thankam1, Victoria E D Wilson2, Mohamed M Radwan1, Aleem Siddique3, Devendra K Agrawal4. 1. Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766, USA. 2. School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland. 3. Division of Cardiothoracic Surgery, University of Nebraska Medical Center, Omaha, NE, USA. 4. Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766, USA. DAgrawal@WesternU.edu.
Abstract
AIMS: Expression status of pro-resolvin lipid mediators (PLM) and receptors in the post-Coronary artery bypass grafting (CABG) coronary arteries are largely unknown. Here, we aim to investigate the expression of the enzymes involved in PLM synthesis and their receptors in the atherosclerotic post-CABG swine (AS) left anterior descending (LAD) compared to without CABG (LAD-AS), and in isolated coronary artery smooth muscle cells (CASMCs) cultured under ischemia. METHODOLOGY: The arteries of interest were harvested from post-CABG atherosclerotic swine and the histomorphology and the expression status of key PLM mediators were quantified using immunostaining. Smooth muscle cells (SMCs) were cultured under ischemia and confirmed the expression on PLM mediators at transcript and protein level. RESULTS: The histomorphometric analysis revealed considerable alterations in the tissue architecture in LAD-CABG and LAD-AS arteries compared to control. PLM synthetic enzyme 5-lipoxygenases (5LO) was significantly upregulated in LAD-CABG and LAD-AS whereas the other enzymes including 12LO, 15LO, and cyclooxygenase-2, and the receptors including Chemokine like receptor 1 (ChemR23), 7-transmembrane G-protein coupled receptor-18 (GPCR18), GPCR120 were decreased in LAD-CABG than control. LO enzymes and PLM receptors were upregulated in ischemic CASMCs with respect to control. Western blot showed the upregulation of 5LO, and ChemR23. Additionally, higher level of resolvin-E1 (RvE1) was observed in ischemic control CASMCs which was decreased following reperfusion. CONCLUSION: These findings suggest that the CASMCs withstand the ischemia-triggered proinflammatory episodes by increasing the secretion of RvE1 mediated through 5LO and ChemR23 signaling.
AIMS: Expression status of pro-resolvin lipid mediators (PLM) and receptors in the post-Coronary artery bypass grafting (CABG) coronary arteries are largely unknown. Here, we aim to investigate the expression of the enzymes involved in PLM synthesis and their receptors in the atherosclerotic post-CABG swine (AS) left anterior descending (LAD) compared to without CABG (LAD-AS), and in isolated coronary artery smooth muscle cells (CASMCs) cultured under ischemia. METHODOLOGY: The arteries of interest were harvested from post-CABG atherosclerotic swine and the histomorphology and the expression status of key PLM mediators were quantified using immunostaining. Smooth muscle cells (SMCs) were cultured under ischemia and confirmed the expression on PLM mediators at transcript and protein level. RESULTS: The histomorphometric analysis revealed considerable alterations in the tissue architecture in LAD-CABG and LAD-AS arteries compared to control. PLM synthetic enzyme 5-lipoxygenases (5LO) was significantly upregulated in LAD-CABG and LAD-AS whereas the other enzymes including 12LO, 15LO, and cyclooxygenase-2, and the receptors including Chemokine like receptor 1 (ChemR23), 7-transmembrane G-protein coupled receptor-18 (GPCR18), GPCR120 were decreased in LAD-CABG than control. LO enzymes and PLM receptors were upregulated in ischemic CASMCs with respect to control. Western blot showed the upregulation of 5LO, and ChemR23. Additionally, higher level of resolvin-E1 (RvE1) was observed in ischemic control CASMCs which was decreased following reperfusion. CONCLUSION: These findings suggest that the CASMCs withstand the ischemia-triggered proinflammatory episodes by increasing the secretion of RvE1 mediated through 5LO and ChemR23 signaling.
Authors: Vasundhara Kain; Kevin A Ingle; Romain A Colas; Jesmond Dalli; Sumanth D Prabhu; Charles N Serhan; Medha Joshi; Ganesh V Halade Journal: J Mol Cell Cardiol Date: 2015-04-11 Impact factor: 5.000
Authors: Madhur P Motwani; Romain A Colas; Marc J George; Julia D Flint; Jesmond Dalli; Angela Richard-Loendt; Roel Ph De Maeyer; Charles N Serhan; Derek W Gilroy Journal: JCI Insight Date: 2018-03-22
Authors: Finosh G Thankam; Joseph G Ayoub; Mohamed M Radwan Ahmed; Aleem Siddique; Thomas C Sanchez; Rafael A Peralta; Thomas J Pennington; Devendra K Agrawal Journal: Transl Res Date: 2020-08-28 Impact factor: 7.012