Pulmonary hypertension (PH) is a disease syndrome that is typified by significant pulmonary vascular remodeling and a progressive elevation of pulmonary vascular resistance. The majority of individuals with PH ultimately succumb to right heart failure. Currently, the overall incidence of pulmonary hypertension in Western countries is estimated to range from 1.1 to 7.6 cases per million people per year, with a 5-year survival rate is even less than 50 % [1], [2], [3], [4]. Despite the growing body of research on the pathogenesis and treatment of pulmonary hypertension, the precise mechanisms underlying its development remain unclear [5], [6], [7]. At present, the most efficacious treatment for advanced pulmonary hypertension remains lung transplantation or combined heart-lung transplantation. However, these approaches face significant challenges in terms of donor availability and economic burden, which impede their broader implementation. Current pharmacological treatment strategies for pulmonary hypertension are primarily aimed at improving endothelial function [7], [8], [9]; however, their efficacy in ameliorating pulmonary vascular remodeling (PVR) and right ventricular hypertrophy (RVH) in advanced-stage patients remains less than ideal. Therefore, it is urgent to find the novel molecular mechanism of PH and implement a targeted therapeutic approach to reverse PVR and RVH, thus improving the prognosis of patients with advanced pulmonary hypertension.

The current literature analysis indicates that majority of nuclear receptors may be associated with occurrence and development of pulmonary hypertension. These include the mineralocorticoid receptor (MR), glucocorticoid receptor (GR), estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), thyroid hormone receptor (THR), vitamin D receptor (VDR), retinoic acid receptor (RAR), farnesoid X receptor (FXR), liver X receptor (LXR), retinoid X receptor (RXR), peroxisome proliferator-activated receptor (PPAR), nuclear receptor 77 (NUR77), nuclear receptor-related 1 (NURR1), neuron-derived orphan receptor 1 (NOR1), and estrogen-related receptor (ERR). Other nuclear receptors, such as retinoid-related orphan receptor (ROR), reverse-ERB (REV-ERB), and small heterodimer partner (SHP), have not been identified as playing a role in pulmonary hypertension. This review aims to summarize the molecular mechanisms of various nuclear receptors involved in the pathogenesis and development of pulmonary hypertension, and to discuss their potential clinical implications based on previous studies.