B1R-TLR4 interactions and their implications in neurogenic hypertension
Grant
Overview
abstract
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Hypertension is the single most predisposing risk factor for cardiovascular disease globally. Despite extensive research establishing hypertension as the primary driver for the development of cardiovascular disease, targeted blood pressure reduction is met in only 50% of hypertensive adults using a combination of readily available antihypertensive drugs, indicating a paramount need for novel therapeutic approaches. We previously showed that B1R activation induces proinflammatory cytokine production and redox imbalance in key autonomic brain regions such as the hypothalamic paraventricular nucleus leading to autonomic dysfunction and hypertension. Studies have shown that TLR4 inhibition in the PVN can attenuate inflammation and hypertension, however, the signaling mechanisms and interactions between B1R and TLR4 have not been studied in models of neurogenic hypertension. Therefore, in this proposal, we test the central hypothesis that B1R blockade will reduce TLR4 mediated signaling mechanisms within the brain, preventing neuroinflammation and mitochondrial dysfunction, thereby attenuating the progression of neurogenic hypertension. This project will identify a novel and vital role for B1R signaling and provide insights for developing novel therapeutics for the treatment of human neurogenic hypertension.
date/time interval
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January 2025 - December 2026
awarded by