Molecular pathways underlying vascular impairment induced by cigarette smoke: unraveling the role of nAChR alpha 7 in hPASMC

Tobacco smoke is the main environmental risk factor for the development of chronic obstructive pulmonary disease (COPD). This chronic disease is a major health concern worldwide. Despite current therapies alleviate symptoms, there remain some limitations in the efficacy of treatments to curb COPD and its cardiovascular morbidities, particularly pulmonary hypertension. Therefore, further study of the cellular and molecular mechanisms underlying this disease is needed for more effective targeted treatment and prevention. Our previous results demonstrate that cigarette smoke has direct effects on pulmonary vascular tone homeostasis and contribute to pulmonary arterial dysfunction. This is in part due to altered activity of the voltage-dependent K+ channel, an exacerbated production of reactive oxygen species and a diminished antioxidant response which promotes a switch in the sGCs redox state. Our current studies aim to delve deeper into the molecular pathways involved in the vascular impairment induced by cigarette smoke exposure and have addressed their contribution to calcium signaling and cellular contractile machinery in pulmonary arteries. We have also addressed whether these effects can be counteracted to improve vascular tone homeostasis. Our results demonstrate deleterious effects on the contractile machinery of pulmonary artery smooth muscle cells. These effects are caused by increased oxidative stress and calcium dysregulation. Furthermore, these signaling pathways could be initiated through the activation of acetylcholine receptor (nAChR) in the pulmonary artery.