Poster #075
Sulforaphane Blocks Olanzapine-Induced Atherosclerosis via PXR Inhibition
Mentors: Changcheng Zhou, PhD; Seunghyun Park, PhD; Jianfei Pan, PhD
Atherosclerosis-linked diseases, driven by chronic vascular inflammation, remain the primary mortality risk worldwide. Recent studies suggest that atypical antipsychotics like olanzapine promote atherogenesis and increase the risk for cardiovascular complications. Here we examine whether sulforaphane (SFN), a bioactive compound from cruciferous vegetables that has recently been shown to have anti-inflammatory properties, can counteract these effects. The pregnane X receptor (PXR) is a nuclear receptor regulating genes associated with lipid metabolism and inflammation. In vitro assays confirmed PXR activation by olanzapine, as well as inhibition by SFN. Using humanized PXR (huPXR) Apoe-deficient mice on a low-cholesterol diet, we found that olanzapine increased aortic root lesion area and that SFN co-treatment reduced lesion size in a PXR-dependent manner in vivo without alteration of body weight. These findings implicate SFN’s protective features against antipsychotic-induced atherogenesis through PXR modulation. Importantly, we gain valuable insight into informing dietary strategies aimed at alleviating the development of atherosclerosis.