A chronic moderate methionine administration induced hyperhomocysteinemia associated with cardiovascular disease phenotype in the sand rat Psammomys obesus

Abstract

Introduction: Cardiovascular diseases were defined as coronary artery, cerebrovascular, or peripheral arterial disease. Hyperhomocysteinemia (Hhcy) is an independent risk factor of cardiovascular diseases, including atherosclerosis. Our previous studies demonstrated the involvement of Hhcy in cardiovascular remodeling in the sand rat Psammomys obesus.

Material and methods: An experimental Hhcy was induced, in the sand rat Psammomys obesus, by a daily intraperitoneal injection of 70 mg/kg of methionine for a total duration of 6 months. The impact of Hhcy on the cellular and matrix structures of the heart, aorta and liver was analyzed using histological techniques. Additionally we treatedprimary cultures of aortic smooth muscle cells (SMCs) with high concentration of methionine to investigate the effects of methionine at the cellular level.

Results: A moderate Hhcy induced a significant increase in the extracellular matrix components particularly collagens which accumulated in the interstitial and perivascular spaces in the studied organs indicating a developing fibrosis. A liver steatosis was also observed following methionine treatment. Further analysis of the aorta showed that Hhcy also induced vascular alterations including SMCs reorientation and proliferation associated with aneurysm formation.

Conclusions: Our results show for the first time that Hhcy can induce a cardiovascular and liver diseases phenotype in Psammomys obesus, a species previously shown to be a good model for the studies of diabetes and other metabolism-related pathologies.

Keywords: Cardiovascular diseases; Hyperhomocysteinemia; Liver; Methionine; Psammomys obesus; SMCs.