NLRP3 Inflammasome: A Novel Mediator in Pulmonary Hypertension

Abstract

Pulmonary hypertension (PH) is marked by elevated mean pulmonary arterial pressure, unfavorable vascular remodeling and right ventricular failure. Current enormous amounts of clinical and preclinical data suggest the role of inflammation as a crucial factor for PH onset and development by modulating both innate and adaptive immune responses. In this context, NLRP3 inflammasome appears as a key step in the signaling cascade that negatively regulates various PH-associated conditions by inducing inflammatory outbursts. The activation of NLRP3 by pathogen-associated molecular pattern molecules/damage-associated molecular pattern molecules and caspase-1 mediated release of proinflammatory cytokines IL-1β and IL-18 are the key molecular events associated with NLRP3 inflammasomal pathway. Released IL-1β and IL-18 bring about adverse consequences on the pulmonary vasculature and the resulting onset of PH. Within this section, we will provide an in-depth understanding of present pulmonary hypertension (PH) treatments and their shortcomings. We will also discuss the contribution of NLRP3 inflammasomes in promoting inflammation within the context of PH pathobiology, as well as explore potential therapeutic approaches to target them.