Cellular senescence in adult pulmonary hypertension: current state and future challenges.

Abstract

Pulmonary hypertension (PH) is a life-threatening disease increasingly being diagnosed in the elderly population, marked by vascular injury, excessive vasoconstriction and progressive remodelling of the pulmonary arteries (PAs). These lead to sustained elevation of PA pressure and subsequent development of right ventricular failure. Despite the beneficial effects on disease progression and quality of life, current treatments do not cure PH, highlighting the need for a deeper understanding of the underlying mechanisms. Recently, cellular senescence has gained much attention as a stress response programme with substantial and somewhat controversial implications for both functional and structural changes within the pulmonary vasculature. Herein, we provide updated insights into the complex role and duelling good and bad effects of senescent cells in the development and progression of PH and discuss the novel therapeutic avenues that this connection opens. Finally, we identify challenges and unmet needs in understanding the two-faced nature of cellular senescence in PH and leveraging senescence therapeutically.