Abstract P287: Hypertension and Danger-associated Molecular Patterns

Abstract

Recent advances in immunobiology have established the importance of endogenous self-molecules or danger-associated molecular patterns (DAMPs) in the initiation of various inflammatory processes as well as the development and progression of atherosclerotic cardiovascular disease (CVD). High-mobility group box 1 (HMGB1) and heat shock protein 72 (Hsp72) are prototypical DAMPs that initiate sterile inflammation, drive inflammatory processes and promote atherogenesis. Hypertension is associated with increased inflammatory burden. The mechanisms underlying blood pressure-related inflammatory stress are not fully understood. It is currently unknown whether DAMPs are dysregulated with elevated blood pressure. Accordingly, the aim of this ongoing study is to determine the influence of hypertension, independent of other risk factors, on circulating expression of HMGB1 and Hsp72. To date, 20 sedentary, middle-aged adults have been studied: 10 normotensive (6M/4F; age: 58±2 yr; BMI: 28.0±1.5 kg/m 2 ; BP: 112/68±2/1 mmHg) and 10 hypertensive (5M/5F; age: 59±1 yr; BMI: 28.1±1.3 kg/m 2 ; BP: 151/92±2/1 mmHg). All subjects were non-smokers, normolipidemic, normoglycemic, non-medicated and free of overt CVD. Plasma concentrations of HMGB1 and Hsp72 were determined by enzyme immunoassay. Circulating concentrations of both HMGB1 (92.2±4.4 vs 69.5±4.3 ng/mL) and Hsp72 (1.6±0.4 vs 0.8±0.1 ng/mL) were significantly higher (35% and 100%, respectively) in the hypertensive compared with normotensive group. HMGB1 concentration was strongly and positively associated with both systolic (r=0.60; p<0.01) and diastolic (r=0.57; p<0.01) blood pressure; whereas Hsp72 was positively correlated with systolic (r=050; p<0.01) blood pressure only. Elevated circulating concentrations of HMGB1 and Hsp72 are consistent with activation of sterile inflammation pathways that, in turn, promote a hyper-inflammatory state. These initial results suggest that dysregulation of DAMPs may contribute mechanistically to the heightened inflammatory burden associated with hypertension and deserve further study.