Angiotensin-(1-7) upregulates expression of adenosine triphosphate-binding cassette transporter A1 and adenosine triphosphate-binding cassette transporter G1 through the Mas receptor through the liver X receptor alpha signalling pathway in THP-1 macrophag

Abstract

Adenosine triphosphate-binding cassette transporter A1 (ABCA1) and ABCG1 play crucial roles in reverse cholesterol transport, and have anti-atherosclerosis effects, and liver X receptor alpha (LXRα) can stimulate cholesterol efflux through these transporters. Angiotensin (Ang)-(1-7) can protect endothelial cells, inhibit smooth muscle cell growth, ameliorate inflammation and exert anti-atherosclerotic effects. In the present study, we attempted to clarify the effect of Ang-(1-7) on expression of ABCA1 and ABCG1, and explored the role of LXRα in the regulation of ABCA1 and ABCG1 in THP-1 macrophages that had been incubated with angiotensin-II (AngII). Ang-(1-7) increased ABCA1 and ABCG1 expression in a concentration-dependent manner at both the mRNA and protein levels, promoted cholesterol efflux, and decreased cholesterol content in THP-1 macrophages treated with AngII. Furthermore, Ang-(1-7) upregulated the expression of LXRα in a concentration-dependent manner in these cells. LXRα small interfering RNA, as well as the Mas receptor antagonist A-779, completely abolished these effects of Ang-(1-7). In summary, Ang-(1-7) upregulates ABCA1 and ABCG1 expression in THP-1 macrophages treated with AngII through the Mas receptor, via the LXRα pathway. This novel insight into the molecular mechanism underlying Ang-(1-7) and AngII interaction could prove useful for developing new strategies for treatment of cardiovascular diseases.

Dyslipoproteinaemia: Important Concern in Type 2 Diabetes

“…Two hormones significantly affect lipid metabolism: adiponectin and insulin. Adiponectin promotes ApoA-I-mediated cholesterol efflux from macrophages by upregulating ABCA1 expression [10]. Adiponectin may directly reduce HDL metabolism and, therefore, is antiatherogenic.…”

Cholesterol Efflux: Does It Contribute to Aortic Stiffening?

“…On the other hand, animal studies reveal that FGF-21 deletion aggravates diabetes-induced aortic remodeling and inflammation in type 1 diabetic mice [ 51 ] and Apo E(−/−) mice [ 52 ]; the blockage of endogenous angiotensin remarkably enhances contents of lipids and macrophages and decreases contents of VSMCs and collagens in aortic lesions in Apo E(−/−) mice [ 53 ]. As suggested by studies showing that angiotensin and FGF-21 enhance cholesterol efflux by upregulating ABCA1 and/or ABCG1 in macrophages [ 54 , 55 ], angiotensin and FGF-21 could act as compensatory mechanisms against arterial stiffness by enhancing cholesterol efflux. A proposed hypothesis is that ABCA1 and/or ABCG1-dependant cholesterol efflux may serve as mediators of arterial stiffness.…”