SY 17-4 NEURO-IMMUNE COMMUNICATION IN HYPERTENSION: A NEW THERAPEUTIC ANGLE?

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Abstract

Hypertension (HTN) is the most prevalent modifiable risk for cardiovascular disease (CVD) and disorders directly influencing CVD (i.e. obesity, diabetes, chronic kidney disease, obstructive sleep apnea, etc.). About one billion people worldwide have HTN, with American adults having 90% lifetime risk of developing HTN. Despite aggressive campaign for lifestyle changes and advances in drug therapy, HTN remains an immense health, emotional, and economic challenge. This is due, in part, to the fact that ∼50% of HTN patients’ blood pressure remains uncontrolled and ∼20% of HTN patients are resistant to or require > antihypertensive drugs. This resistant HTN (R-HTN) is primarily neurogenic in origin, and is characterized by dysfunctional autonomic nervous system with heightened inflammatory and neuroinflammatory profiles. Unfortunately, few treatment options are available for such patients at the present time. We have proposed a novel hypothesis for the development and establishment of R-HTN, validation of which could offer an innovative strategy for the treatment of this group of patients. We propose that a brain-bone marrow (BM) communication is critical in the maintenance of vascular repair and inflammatory status of the cardiovascular system. Autonomic-medicated increase in the sympathetic nerve activity to the BM (sSNA) impairs this balance resulting in an increased production of proinflammatory progenitor cells and decrease in angiogenic progenitor cells. This increases peripheral inflammatory status and compromises vascular repair capabilities, hallmarks of HTN. Furthermore, some of the proinflammatory progenitor cells extravasate into the autonomic brain regions, differentiate into activated microglia, and contribute to neuroinflammation. Neuroinflammation-induced release of cytokines, chemokines, ROS, etc. further elevates autonomic neuronal activity. This perpetual cycle of increased sSNA, proinflammatory progenitors, and neuroinflammation are critical events in the establishment of R-HTN. Evidence will be presented in support of this hypothesis. In addition, we will present the concept that minocycline-based anti-inflammatory molecule could be a potential target for drug development for R-HTN.

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