Research Article Open Access Clinical & Experimental Cardiology Hadi et al., J Clin Exp Cardiolog 2013, 4:6 http://dx.doi.org/10.4172/2155-9880.1000249 Volume 4 • Issue 6 • 1000249 J Clin Exp Cardiolog ISSN: 2155-9880 JCEC, an open access journal *Corresponding author: Najah R Hadi, Department of Pharmacology and Therapeutics, Kufa College of Medicine, Kufa, po: 21, Iraq, Tel: 009647801241456; E-mail: drnajahhadi@yahoo.com Received May 02, 2013; Accepted June 10, 2013; Published June 12, 2013 Citation: Hadi NR, Abdulkadhim H, Almudhafer A, Majeed SA (2013) Effect of Vildagliptin on Atherosclerosis Progression in High Cholesterol –Fed Male Rabbits. J Clin Exp Cardiolog 4: 249. doi:10.4172/2155-9880.1000249 Copyright: © 2013 Hadi NR, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Background: Atherosclerosis is a progressive disease of large and medium-sized arteries characterized by the accumulation of lipids and fbrous elements in the large arteries. Aim of the study: This study was undertaken to assess the effect of vildagliptin on the progression of atherosclerosis via interfering with infammatory and oxidative pathways. Materials and Methods: 18 local domestic male rabbits were included in this study. The animals were randomly divided into three groups (6 rabbits for each group): Group I rabbits fed normal chow (oxiod) diet for 12 weeks. Group II rabbits fed 1% cholesterol enriched diet for 12 weeks. Group III rabbits fed with cholesterol enriched diet for 6 weeks, and then continued on cholesterol-enriched diet and treated with vildaglipin 50 mg/kg/day orally for the next 6 weeks. Blood samples were collected at the start of the study, at 6weeks of the study and then at the end of treatment course to measure Serum lipids profle [(TC), (TG), (HDL)], hsCRP and TNFα. At the end of the study the aorta were removed for measurement of aortic MDA, glutathione, sectioning for histopathology and measuring aortic intima- media thickness. Results: Treatment of rabbits with vildagliptin for 6 weeks results in a signifcant reduction (P<0.05) in serum level of TC, TG, hsCRP and TNFα and a signifcant increase (P<0.05) in serum HDL level. There was a signifcant reduction (P<0.05) in aortic MDA and intima-media thickness, in comparison to the rabbits in the induced untreated control group. vildagliptin treatment cause signifcant increment (P<0.05) in aortic GSH in comparison to induced untreated group. Regarding the histopathological results, vildagliptin treatment for 6 weeks results in a signifcant reduction (P<0.05) in atherosclerotic lesions in comparison to the induced untreated group and signifcant reduction in aortic intima- media thickness (P<0.05). Conclusions: Vildagliptin reduced atherosclerosis progression in hyperlipidemic rabbit via its effect on lipid parameters and interfering with infammatory and oxidative stress pathway. Effect of Vildagliptin on Atherosclerosis Progression in High Cholesterol –Fed Male Rabbits Najah R Hadi*, Hussain Abdulkadhim, Ahmad Almudhafer and Sahar A Majeed Department of Pharmacology and Therapeutics, Kufa College of Medicine, Kufa, po: 21 Iraq Keywords: Vildagliptin; Atherosclerosis; Oxidative stress; Infammation Background Atherosclerosis is a multifactorial, multistep disease that involves chronic infammatory at every stage, from initiation to progression and, eventually, plaque rupture [1]. Cardiovascular disease (CVD) is the principal cause of death and disability in developed countries and is increasing rapidly in the developing world [1,2]. Endothelial dysfunction is the early step that allows dissemination of lipids and infammatory cells into the endothelial and sub-endothelial spaces. Secretion of cytokines and growth factors promote SMC proliferation, accumulation of collagen matrix, monocytes infltration, and other white blood cells, forming an atheroma [3]. Incretin hormones Te role of the gastrointestinal tract in regulating the secretion of insulin is demonstrated by the thought that insulin secretion is substantially increased in response to oral glucose load, compared to intravenous glucose administration. Tis diference is known as the incretin efect; these peptides are secreted from endocrine cells (L-cells) in the gastrointestinal tract, and are released in response to ingestion of food and subsequent oral glucose load. Te two main incretin hormones are glucagon-like peptide-1 (GLP-1) and glucose- dependent insulinotropic polypeptide (GIP). Dipeptidyl peptidase- IV (DDP-IV) is proteolytic enzyme that is widely expressed in many tissues, including the capillary bed of the gut mucosa and is responsible for rapid inactivation of (GLP-1) [4]. In cretin-like agents and DPP- 4 inhibitors show the need to act on the underlying disease rather than on its symptoms. Tey enhance glucose-dependent insulin secretion by pancreatic beta cells, and consequently there is less risk of hypoglycemia. Tey also suppress elevated glucagon secretion and increase feeling of satiety. It has been theorized that they may reestablish beta-cell sensitivity to glucose, which could mean that they may be able to delay the onset of type 2 diabetes, slow its progression, and reduce its cardiovascular and metabolic complications [5]. Vildagliptin is a potent, reversible, competitive inhibitor of DPP-4, with high selectivity for DPP-4 over other peptidases enzymes [6]. Materials and Methods Eighteen local domestic male rabbits were included in this study. Te animals were randomly divided into three groups (6rabbits in each group): Group I rabbits fed normal chow (oxiod) diet for 12 weeks. Group II rabbits fed 1% cholesterol enriched diet for 12 weeks. Group