PMID- 25037058 OWN - NLM STAT- MEDLINE DCOM- 20150707 LR - 20211021 IS - 1753-9455 (Electronic) IS - 1753-9447 (Print) IS - 1753-9447 (Linking) VI - 8 IP - 6 DP - 2014 Dec TI - Adiponectin expression and the cardioprotective role of the vitamin D receptor activator paricalcitol and the angiotensin converting enzyme inhibitor enalapril in ApoE-deficient mice. PG - 224-36 LID - 10.1177/1753944714542593 [doi] AB - BACKGROUND: Coronary heart disease (CHD) is the number one cause of death in the US. The adipokine adiponectin has been studied intensively for presenting and inversed association with almost every stage of CHD. For instance, the evaluation of molecules capable of enhancing endogenous adiponectin expression is well justified. In this study, we investigated the effect of the vitamin D receptor activator (VDRA) paricalcitol and the angiotensin-converting enzyme inhibitor (ACEI) enalapril on adiponectin expression, lipid profiles, adenosine monophosphate activated protein kinase (AMPK) expression, monocyte chemo-attractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNFalpha),cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), antioxidant capacity, CuZn-superoxide dismutase (CuZn-SOD), Mn-SOD, NADPH p22phox subunits, inducible nitric oxidesynthase (iNOS), endothelial marker eNOS, and 81 atherosclerosis-related genes in ApoE-deficient mice. METHOD: Seven-week-old ApoE-deficient mice were treated for 16 weeks as follows: Group 1, ApoE vehicle control (intraperitoneal [i.p.] 100 microl propylene glycol); Group 2, ApoE-paricalcitol (200 ng i.p., 3/week); Group 3, ApoE-Enalapril (30 mg/kg daily); Group 4, ApoE-paricalcitol + enalapril (described dosing); and Group 5, wild-type control (C57BLV). RESULTS: All treated groups presented significant changes in circulating and cardiac adiponectin, cardiac cholesterol levels, AMPK, MCP-1, TNF-alpha, COX-2, iNOS, eNOS, CuZn-SOD, Mn-SOD and p22phox. There were 15 genes that differed in their expression, 5 of which are involved in cardioprotection and antithrombotic mechanisms: Bcl2a1a, Col3a1, Spp1 (upregulated), Itga2, and Vwf (downregulated). CONCLUSION: Together, our data presented a novel role for VDRA and ACEI in reducing factors associated with CHD that may lead to the discovery of new therapeutic venues. CI - (c) The Author(s), 2014. FAU - Suarez-Martinez, Edu AU - Suarez-Martinez E AD - Department of Biology, University of Puerto Rico in Ponce, PO Box 7186, Ponce, PR 00732, USA esuarez@psm.edu. FAU - Husain, Kazim AU - Husain K AD - Department of Physiology, Pharmacology, and Toxicology, Ponce School of Medicine and Health Sciences, PO Box 7004, Ponce, PR 00732, USA. FAU - Ferder, Leon AU - Ferder L AD - Department of Physiology, Pharmacology, and Toxicology, Ponce School of Medicine and Health Sciences, PO Box 7004, Ponce, PR 00732, USA. LA - eng GR - G12 RR003050/RR/NCRR NIH HHS/United States GR - G12RR003050/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140718 PL - England TA - Ther Adv Cardiovasc Dis JT - Therapeutic advances in cardiovascular disease JID - 101316343 RN - 0 (Adiponectin) RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Apolipoproteins E) RN - 0 (Ergocalciferols) RN - 0 (Receptors, Calcitriol) RN - 63231-63-0 (RNA) RN - 6702D36OG5 (paricalcitol) RN - 69PN84IO1A (Enalapril) SB - IM MH - Adiponectin/biosynthesis/*genetics MH - Angiotensin-Converting Enzyme Inhibitors/pharmacology MH - Animals MH - Apolipoproteins E/deficiency MH - Blotting, Western MH - Coronary Artery Disease/genetics/metabolism/*prevention & control MH - Disease Models, Animal MH - Drug Therapy, Combination MH - Enalapril/*pharmacology MH - Ergocalciferols/*pharmacology MH - Female MH - *Gene Expression Regulation MH - Mice MH - Mice, Inbred C57BL MH - Oxidative Stress MH - Polymerase Chain Reaction MH - RNA/*genetics MH - Receptors, Calcitriol/*drug effects/metabolism PMC - PMC4389636 MID - NIHMS671778 OTO - NOTNLM OT - Adiponectin OT - Enalapril OT - Inflammatory markers OT - Oxidative Stress OT - Paricalcitol OT - VDRA OT - cardio-protection COIS- Conflict of interest statement: The authors declare no conflict of interest in preparing this article. EDAT- 2014/07/20 06:00 MHDA- 2015/07/08 06:00 PMCR- 2015/04/08 CRDT- 2014/07/20 06:00 PHST- 2014/07/20 06:00 [entrez] PHST- 2014/07/20 06:00 [pubmed] PHST- 2015/07/08 06:00 [medline] PHST- 2015/04/08 00:00 [pmc-release] AID - 1753944714542593 [pii] AID - 10.1177/1753944714542593 [doi] PST - ppublish SO - Ther Adv Cardiovasc Dis. 2014 Dec;8(6):224-36. doi: 10.1177/1753944714542593. Epub 2014 Jul 18.