Elevated luteinizing hormone contributes to atherosclerosis formation by inhibiting nitric oxide synthesis via PI3K/Akt pathway

Background: The contentious effects of estrogen therapy on the risk of postmenopausal cardiovascular disease (CVD) indicate that this type of atherosclerosis is not solely induced by estrogen deficiency. Other sex hormones such as elevated luteinizing hormone (LH) may also affect CVD risk in this population. We therefore explored the relationship between LH and atherosclerosis in ovariectomized (OVX) female mice. Methods: Aortic atherosclerotic lesions were assessed in OVX ApoE knock out (ApoE(-/-)) female mice administered with LH. Human umbilical vascular endothelial cells (HUVECs) were cultured as cell model. The influence of LHon NO release, phosphorylated endothelial nitric oxide synthase (eNOS) and Akt levels were evaluated. Immunoprecipitation and lentiviral particle transfection were applied to assess the role of G alpha q on PI3K activity. Results: LH increased the atherosclerotic lesion area and carotid artery intima-media thickness (IMT) in OVX ApoE(-/-) female mice. High levels of LH attenuated vasodilation induced by Ach and inhibited NO release from HUVECs. These effects were related to the findings that LH enhanced interaction between Gaq and p110 alpha, which subsequently inhibited PI3K activity and suppressed the phosphorylation of Akt and eNOS. Conclusions: Elevated LH promotes atherosclerosis formation in OVX ApoE(-/-) female mice. This effect may be mediated by inhibiting endothelial NO synthesis via PI3K/Akt signaling pathway.