7A.04

Abstract

Objective: Obesity is the most important risk factor for hypertension (HTN) and they are strongly associated with chronic inflammation. Treatment resistant hypertension (TRH) subjects, accounting for ∼20% of HTN, have high levels of inflammatory cytokines. This coupled with the fact that the role of adipose stem cells (ASCs) in obesity associated TRH has not been investigated, led us to hypothesize that ASCs from obese-HTN patients expressing heightened inflammatory cytokines contribute to pathogenesis of TRH. Thus, we aim to determine the relationship between ASCs, inflammation, obesity, and TRH. Design and method: 611 Subjects from the Women's Ischemia Syndrome Evaluation (WISE) study were grouped to normotensive [N, n=99, systolic BP (SBP) 120 ± 12mmHg], controlled HTN (CH, n = 247, SBP 123 ± 11mmHg), and TRH (n = 48, SBP 158 ± 21mmHg). Sera from these subjects were analyzed for high sensitive C-reactive protein (CRP), IL6, serum amyloid A (SAA) and TNF-α level. Human ASCs (hASCs, CD90+/CD11b-/HLA-DR-) were cultured from subcutaneous adipose tissues of overweight-normotensive (ON, n = 6) or obese-hypertensive subjects (OH, n = 6). Rat ASCs (rASCs, CD44+/CD90+/CD34-/CD45-) were isolated from inguinal adipose tissue of normotensive,WKY rats and spontaneously hypertensive rats (SHR). Results: BP positively correlated with the levels of inflammatory cytokines for the WISE analysis. TRH showed two-fold higher CRP (median 0.7), 1.8-fold more IL-6 (median 4.0) and 50% elevated SAA (median 0.8) than N and CH. Additionally, body mass index (BMI) was significantly associated with levels of CRP(r = 0.25, p = 0.0001), IL6(r = 0.14, p = 0.0003), and SAA(r = 0.12, p = 0.0004). hASCs from OH subjects have higher TNF-α, ROS and proliferative capacities than ON subjects. Likewise, rASCs from SHR demonstrated notably higher levels of inflammatory cytokine (TNF-α and IL-1β), ROS and proliferation than WKYrats. Conclusions: Although the magnitude of correlation differed, there was significant positive correlation among BMI, BP, and levels of inflammatory cytokines. Obese subjects are more likely to have TRH than those with lower BMI. Hyper-proliferative ASCs could contribute to elevated inflammation status. These findings imply that ASCs and inflammation plays a critical role in the BP control. Thus, BMI and inflammation status of serum and stem cells may be useful predictors for TRH.