New indole-thiazolidine attenuates atherosclerosis in LDLr-/- mice

Author(s)

Cesar, Fernanda A. ^[1] ; Rudnicki, Martina ^[1] ; de las Heras, Beatriz ^[2] ; Bosca, Lisardo ^[3] ; Lima, Maria C. A. ^[4] ; Pitta, Ivan R. ^[4] ; Abdalla, Dulcineia S. P. ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo, SP - Brazil

^[2] Univ Complutense Madrid, Fac Pharm, Dept Pharmacol, Madrid - Spain

^[3] CSIC UAM, Inst Invest Biomed Alberto Sols, Madrid - Spain

^[4] Univ Fed Pernambuco, Ctr Hlth Sci, Recife, PE - Brazil

• Document type: Journal article
• Source: VASCULAR PHARMACOLOGY; v. 71, p. 174-180, AUG 2015.
• Web of Science Citations: 4

Abstract

Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists that improve insulin-mediated glucose uptake and possess beneficial vasculoprotective actions. However, because undesirable side effects are associated with these drugs, novel TZDs are under development. In this study, we evaluated the biological activity of LYSO-7, a new indole-thiazolidine, on PPAR activation, inflammation and atherogenesis using a gene reporter assay, lipopolysaccharide (LP5)-activated RAW 264.7 cell culture, and a low-density lipoprotein receptor knockout (LDLr-/-) mouse model of atherosclerosis. LYSO-7 shows low cytotoxicity in RAW 264.7 cells and at 2.5 mu mol/L induces PPAR alpha and PPAR gamma transactivation as well as inhibits LPS-induced nitrite production and the mRNA gene expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1). In addition, treatment with LYSO-7 reduces the development of atherosclerosis in LDLr-/- mice, improves the lipid profile, blood glucose levels, and downregulates CD40 and CD40L expression without affecting the body weight of the animals. Altogether, our data show that LYSO-7 possesses anti-inflammatory properties and that treatment with this TZD attenuates atherosclerosis progression in LDLr-/- mice by modulating lipid metabolism and inflammation. Thus, LYSO-7 shows potential as a new drug candidate for the treatment of atherosclerosis. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 12/51316-5 - Study of the activity of biodrugs, PPARs agonists and natural products with therapeutic potential in atherosclerosis
• Grantee: Dulcineia Saes Parra Abdalla
• Support Opportunities: Research Projects - Thematic Grants