Nuclear receptors in pulmonary hypertension: From pathophysiological mechanisms to clinical implications

Pulmonary hypertension is one of the most intractable cardiovascular diseases in the world today. The current pharmacological treatments can temporarily relieve symptoms, but the therapeutic effect is unsatisfactory in advanced pulmonary hypertension with severe pulmonary vascular remodeling and right ventricular hypertrophy. The nuclear receptor superfamily is a vital class of transcriptional regulators in the human body. Extensive research has demonstrated that these regulators play pivotal roles in a multitude of physiological processes and are involved in the regulation of the pathogenesis of a variety of pathological diseases, providing potential therapeutic targets for pulmonary hypertension. The targeting of nuclear receptors, such as MR, PPARγ, and NUR77, has demonstrated potential in improving pulmonary vascular remodeling and preventing the progression of experimental pulmonary hypertension. However, further in-depth mechanistic exploration and large-scale preclinical studies are necessary to facilitate eventual clinical application. In this review, we describe in detail the various types of nuclear receptors that affect the function of pulmonary vascular endothelial cells and smooth muscle cells by regulating inflammation, oxidative stress, metabolism, and other processes, thereby affecting the prognosis of pulmonary hypertension, and highlight the clinical therapeutic potential of nuclear receptors. Intensive research on the regulatory role of nuclear receptors in pulmonary hypertension has yielded new avenues for targeted therapy of pulmonary hypertension and has prompted the exploration of new therapeutic strategies to combat this life-threatening disease.