Hypothyroidism induces the expression of atherosclerosis markers in Psammomys obesus

Abstract

Thyroid hormones (TH) have several effects on the cardiovascular system. A slight decline in TH levels has harmful effects on the vascular system. The current study aimed to investigate whether a decrease in TH plasma levels was responsible for the expression of some atherosclerosis markers. Experimental hypothyroidism was induced in Psammomys obesus by administering 0.03% carbimazole in their drinking water for five months (M5). The animals were sacrificed at M5, and histopathological analysis of the thoracic aorta and thyroid gland was performed after Masson's trichrome staining. The expression of the angiotensinogen (Agt) gene and the genes implicated in cholesterol metabolism regulation in the liver and vascular smooth muscle cells (VSMCs) was determined by qRT-PCR. Finally, we assessed the in vitro proliferation rate of VSMCs derived from the aortas of the two groups of animals. Hypothyroidism was associated with increased expression of Agt in the liver and 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr) and Acyl CoA:cholesterol acyltransferase (Acat) 1 genes (cholesterol synthesis and esterification pathway) in VSMCs, with failure to increase efflux pathway genes (ATP-binding cassette subfamily G member (Abcg) 1 and 4) in these vascular cells. Moreover, reduction in TH induces aortic endothelial cell and subendothelium hypertrophy, and disorganization of the media with rupture of the elastic fiber network. All these results suggest that hypothyroidism can lead to atherosclerosis through the alteration of the physiology of VSMCs, mainly the phenotype switch and gene expression modification involved in the regulation of cholesterol metabolism.