Abstract P246: Sex Differences In The Association Between Soluble Prorenin Receptor And Physiological And Cardiometabolic Risk Factors In Healthy Humans Varying In Age And Obesity

Abstract

The prorenin receptor (PRR), which regulates renin-angiotensin system in multiple tissues, can be cleaved to generate soluble PRR (sPRR) in plasma. sPRR concentrations vary with clinical conditions such as metabolic syndrome, pregnancy, chronic kidney disease and heart failure in humans. However, whether sPRR is associated with aging and healthy obesity in men and women is unknown. We aimed to evaluate if there are sex-specific associations of sPRR with cardiometabolic risk factors among healthy women and men varying in age and obesity. Circulating cardiometabolic, vascular and inflammatory risk factors and sPRR (via ELISA) were measured in unmedicated healthy men (n=55; age 39 ± 16 yrs; BMI 29 ± 4 kg/m2) and women (n=34; age 44 ± 16 yrs; BMI 30 ± 7 kg/m2) at the University of Iowa. Women were classified by menopausal status [pre-menopausal, pre-M (n=18) and post-menopausal, post-M (n=16)]. Independent t -test was used to compare means and pearson correlation was examined. In men, sPRR was not related to age, systolic blood pressure (SBP), BMI, cholesterol or endothelial function (brachial artery flow mediated dilation, FMD), but was correlated with plasma TNFα (r=0.50, P<0.05). sPRR was higher in overweight/obese (BMI ≥ 25 kg/m2) compared with non-obese men (n=48; 10.8 ± 0.4 vs. n=7; 8.3 ± 0.4 ng/ml, P<0.05). In women, sPRR did not correlate with BMI or SBP, but correlated with total cholesterol (r=0.49, P<0.05) and TNFα (r=0.49, P<0.05). sPRR correlated with age in women with a BMI<30 (r=0.54, P<0.05) but not a BMI ≥30 kg/m2. sPRR was significantly higher in post-M compared with Pre-M women independent of obesity or hypertension status (12.1 ± 0.5 vs. 10.1 ± 0.4 ng/ml, P<0.05). sPRR correlated with FMD only in obese women (%FMD: r=-0.50, P<0.05), indicating a relation of sPRR with endothelial dysfunction in obese women. Interestingly, sPRR was significantly higher in Pre-M compared with non-obese men and menopause further exacerbated the difference. In conclusion, sPRR is associated with TNFα in both men and women, but there are sex differences in the relation with BMI, age, cholesterol and endothelial function in humans. sPRR concentrations were higher in post-M compared with pre-M women, suggesting that PRR could contribute to cardiovascular risk in post-M women.