Poster #014, Charles R. Drew University of Medicine and Science
Follistatin Inhibition of α7 Nicotinic Acetylcholine Receptor during Electronic Cigarette-Induced Atherosclerosis
Mentor: Rajan Singh, PhD
Electronic cigarettes (E-Cigs) are increasingly linked to elevated cardiovascular disease risk in adolescents and adults. Nicotine, the primary bioactive component of E-Cigs, promotes atherosclerosis largely through the activation of the α7-nicotinic acetylcholine receptor (α7-nAChR). Specifically, activation of the α7-nAChR, pERK1/2, and Snail-mediated signaling pathways plays a critical role in driving endothelial-to-mesenchymal transition (EMT) and remodeling, thereby promoting nicotine- and smoking-induced atherosclerosis. Because the downstream mechanisms governing this pathology remain poorly characterized, identifying novel molecular inhibitors of α7-nAChR is critical to mitigating E-Cig-induced vascular damage. We investigated the effects of nicotine-containing JUUL aerosol on α7-nAChR expression and its downstream target, phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), in human aortic endothelial cell (HAEC) cultures, while evaluating the therapeutic potential of Follistatin (Fst). In vitro cell culture studies were conducted using HAECs exposed to JUUL aerosol (5% nicotine) bubbled cell culture medium in the presence or absence of recombinant Fst protein. Molecular and phenotypic changes in the treated cells were quantified via Western blot analysis to evaluate specific protein expression levels. Exposure of JUUL-bubbled cell culture media significantly upregulated the expression of α7-nAChR and its downstream signaling target pERK1/2 within the endothelial cultures. Treatment with recombinant Fst protein (0.5μg/ml) markedly reversed these JUUL-induced effects, effectively suppressing JUUL-induced upregulation of both α7-nAChR and pERK1/2 protein expression levels back toward baseline. Follistatin effectively inhibits JUUL/nicotine-induced activation of α7-nAChR, and its downstream target pERK1/2 known to contribute during the progression of electronic cigarette/nicotine-induced atherosclerosis. These preliminary findings suggest that follistatin may serve as a promising therapeutic agent to counteract E-Cig-mediated endothelial dysfunction and subsequent cardiovascular risk.