Connecting the Dots: Nlrp3 Inflammasome As a Key Mediator in the Intersection of Depression and Cardiovascular Disease – a Narrative Review Publisher



Jahromi GG^{1, 2} ; Rezaei N^{2, 3, 4, 5} Show Affiliations
Source: Heart and Mind Published:2025

Abstract

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide and frequently coexist with depressive disorders. The consequence of their concurrence is the exacerbation of both conditions. Numerous studies seek to understand the pathophysiological connection between this mental disorder and CVDs, and theories such as autonomic dysfunction, endocrine dysregulation, platelet dysfunction, and inflammation have been suggested. However, in this review, we propose that these theories are all related and that etiology of both diseases can be explained by the involvement of the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome-mediated inflammation. To elucidate, we investigate the inflammasome contribution to the central nervous system (CNS), the vasculature, the heart, and the autonomic nervous system. We presented evidence of neurotransmitter imbalances, hypothalamic pituitary adrenal axis dysregulation, microglial activation, and inflammatory damage to the CNS. We put forward the research on NLRP3 activation showing vascular damage that could alter the brain blood barrier, cause endothelial dysfunction, alter lipid metabolism, hypertension, atherosclerosis, aneurisms, and hypercoagulable states. Similarly, we explore its involvement in the development of heart failure, cardiac remodeling, myocardial infarction, cardiac arrythmias, and hyperactive tuning of the sympathetic response. © 2025 Heart and Mind | Published by Wolters Kluwer - Medknow.