Role of NLRP-3 Inflammasome in Hypertension: A Potential Therapeutic Target

Abstract

Background: Hypertension is a multifactorial and chronic cardiovascular condition whose complications are responsible for worldwide morbidity and mortality. An increasing body of experimental data, recognize low-grade inflammation as a basic process in hypertension onset and development since there is a strong contribution of both the innate and the adaptive immune system according to the so-called Danger-Model. In this contest, NLRP3 inflammasome represents a key signaling platform as demonstrated by its implication in several hypertension-associated conditions, such as vascular smooth muscle remodeling and proliferation. This intracellular receptor is activated by Pathogenassociated molecular pattern molecules/damage-associated molecular pattern molecules signals and its mechanism of action converges on the final production of caspase-1 and, consequently, of the proinflammatory cytokines IL-1β and IL-18.

Objective: The aim of the present work was to point out the role of the NLRP3 inflammasome complex in the hypertensive pathology and to describe it as a new potential therapeutic target.

Method: A systematic review of the literature data related to NLRP3 and hypertension correlation has been performed.

Results: Numerous and well-designed experiments demonstrate that the inflammasome plays a crucial role in essential and high-salt dependent hypertension, as well as in preeclampsia, in pulmonary hypertension, and in its related secondary disorders; its mechanism includes both a central nervous and a peripheral modulation of the inflammatory pathways. To date, research is trying to design inflammasome antagonists or equivalent inhibition strategies.

Conclusion: The inflammasome represents a leading promoter of hypertensive inflammation opening new perspective in the field of the clinical approach in this pathology.

Keywords: Cytokines; hypertension; inflammasome; inflammation; preeclampsia; vascular remodeling..