The roles of endothelin and its receptors in cigarette smoke-associated pulmonary hypertension with chronic lung disease

Chronic exposure to cigarette smoke is the major risk factor for the development of pulmonary hypertension (PH) with chronic lung disease (i.e. PH group III). The pathogenesis of smoke-associated PH group III in chronic obstructive pulmonary disease (COPD) involves cigarette smoke exposure-induced damage to lung tissue and dysfunction of pulmonary system with increased synthesis and release of endothelin-1 (ET-1), hypoxia, inflammation, pulmonary vascular remodeling. Many studies have demonstrated that cigarette smoke exposure induces activation of mitogen-activated protein kinase (MAPK) signal pathway that leads to up-regulation of ET-1 and its receptors with the receptor-mediated enhanced contraction, proliferation of pulmonary vascular smooth muscle cells, pulmonary vascular remodeling, elevated pulmonary arterial pressure and finally PH group III. This mini-review article aims to summarize the current state of understanding on the roles of cigarette smoke-induced up-regulation of ET-1 and its receptors in the development of PH group III. Understanding the underlying molecular mechanisms that cigarette smoke exposure leads to PH group III may provide a novel strategy for the treatment.