Background Coronary heart disease (CHD) is the number one cause of death in the US. (MCP-1) tumor necrosis factor-alpha (TNFα) cyclooxygenase-2 (COX-2) inducible nitric oxide synthase (iNOS) antioxidant capcity 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 μl propylene glycol); Group 2 ApoE-paricalcitol (200 ng i.p. 3 Group 3 ApoE-Enalapril (30 mg/kg daily); Group 4 ApoE-paricalcitol + enalapril (described dosing); and Group 5 17-AAG (KOS953) wild-type control (C57BLV). Results All treated groups presented significant changes in circulating and cardiac adiponectin cardiac cholesterol levels AMPK MCP-1 TNF-α COX-2 iNOS eNOS CuZn-SOD Mn-SOD and p22phox. There were 15 genes that differed in their expression 17-AAG (KOS953) 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 17-AAG (KOS953) for VDRA and ACEI in reducing factors associated with CHD that may lead to the discovery of new therapeutic venues. 2013 Several studies have shown an inverse association between circulating adiponectin levels and the development of CHD at almost every stage [Nimitphong 2009; Gannage-Yared 2009; Trujillo 2005; Lam 2005]. This multimeric peptide hormone has been proposed as a key effector in insulin sensitivity and lipid metabolism promoting weight loss and the reduction of triglycerides even when combined with a high-fat diet [Tsatsanis 2006; Ouchi 2003; Yamauchi 2001]. In homozygous Apo-lipoprotein E-deficient mice (ApoE-) adiponectin treatment (either globular or adenovirus-mediated) decreased the atherosclerotic-lesion formation [Ouchi 2006; Hopkins 2007; Okamoto 2002]. Adiponectin protects against vascular disorders as observed in a mouse model of spontaneous atherosclerosis [Yamauchi 2003]. It also prevents almost every pathogenic event involved in atherosclerotic plaque formation by augmenting the 17-AAG (KOS953) endothelial nitric oxide (NO) production [Ouchi 2003; Arita 2002] reducing oxidative stress [Ouedraogo 2006; Motoshima 2004; Tao 2007; Furukawa 2004; Nakanishi 2005] inhibiting endothelial cell activation [Kobashi 2005; Tan 2004] suppressing leukocyte-endothelium interaction [Ouedraogo 2006; Ouedraogo 2007; Joussen 2004] inhibiting macrophage activation and foam cell formation [Park 2007; Masaie 2007; Peake 2006; Kumada 2004] regulating phagocytosis [Takemura 2007; Saijo 2005] antithrombotic activities [Shoji 2006; Kato 2006] and inhibiting smooth muscle proliferation [Okamoto 2002; 17-AAG (KOS953) Hansmann 2007; Wang 2005; Kubota 2002]. For instance the identification of molecules that increase the production of endogenous adiponectin and as DHCR24 a consequence its cardioprotective effects would have a direct impact on the current strategies for preventing CHD. In this study we investigated the effect of the vitamin D receptor activator (VDRA) paricalcitol and angiotensin-converting enzyme inhibitor (ACEI) enalapril in the production of adiponectin in an atherosclerosis mouse model and evaluated the downstream influence on lipids profile macrophage chemo-attractant protein (MCP-1) tissue necrotic factor-alpha (TNF-α) cyclo-oxygenase 2 (COX-2) NADPH p22phox subunit inducible nitric oxide synthase (iNOS) endothelial nitric oxide synthase (eNOS) superoxide dismutases (CuZn-SOD and Mn-SOD) adenosine monophosphate-activated protein kinase (AMPK) and 81 atherosclerosis-related markers in the heart of the atherosclerosis model of ApoE deficient mice. Materials and methods Chemicals Enalapril was purchased from Sigma Chemical Company (St Louis MO USA) and VDRA (paricalcitol) was provided by Abbott Pharmaceuticals (Abbott Park IL USA). EnzyChrom Cholesterol Assay Kit (ECCH-100) EnzyChrom Triglyceride Assay Kit (ETGA-200) and EnzyChrom HDL and LDL/VLDL Assay Kit were purchased from BioAssay Systems (Hayward CA USA). Adiponectin kit was purchased from R&D Systems (Minneapolis MN USA). Antibodies were purchased from Santa Cruz Biotechnology Santa Cruz CA USA and Abcam.