Hypertension resulting from overexpression of translationally controlled tumor protein increases the severity of atherosclerosis in apolipoprotein E knock-out mice

Abstract

Hypertension is a well-established etiological factor for atherogenesis. We previously showed that transgenic mice overexpressing translationally controlled tumor protein (TCTP) develop systemic arterial hypertension. In this study we explored the cardiovascular effects of TCTP overexpression and possibly of the resultant hypertension on the severity of atherosclerosis in apolipoprotein E-deficient mice. Through multiple mating of TCTP-overexpressing transgenic mice (TCTP-TG) with apolipoprotein E knock-out mice (ApoE KO), we generated non-transgenic (nTG), TCTP-TG, nTG/ApoE KO and TCTP-TG/ApoE KO mice with similar genetic background. Male mice, 7-week old, were fed a lipid-enriched Western diet for 16 weeks, and blood pressure and body weight change were monitored every 2 weeks. Plasma lipid profiles and atherosclerotic lesions in aorta were quantified at the end of study. We found that blood pressure levels of TCTP-TG and TCTP-TG/ApoE KO, were similarly elevated while nTG and nTG/ApoE KO mice were normotensive. TCTP overexpression in ApoE KO mice led to significant exacerbation of atherosclerotic lesions. Feeding Western diet resulted in increases in total cholesterol, triglyceride (TG) and low density lipoprotein, and decreased high density lipoprotein (HDL) in ApoE KO mice. No significant differences were found in plasma lipid profiles of nTG/ApoE KO and TCTP-TG/ApoE KO. This study suggests that overexpression of TCTP, which induces hypertension, also accelerates the development of atherosclerotic lesion caused by high-fat and high-cholesterol diet without significantly altering plasma lipid profiles. We conclude that TCTP-induced hypertension could increase the severity of atherosclerotic lesion and suggest that inhibition of TCTP or its signaling pathways may be a potential approach to the therapy of both diseases, hypertension and atherosclerosis.