Browsing by Author "Wenner, Megan M."
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Item Antecubital venous endothelial ETB receptor protein expression is preserved with aging in men(American Journal of Physiology - Heart and Circulatory Physiology, 2024-01-01) Tummala, Saumya; Kuczmarski, Andrew V.; Del Vecchio, Angelica R.; Schwab, Allyson I.; Edwards, David G.; Wenner, Megan M.Changes in endothelial function precede the development of cardiovascular disease (CVD). We have previously shown that age-related declines in endothelial function in women are due in part to a reduction in endothelial cell endothelin-B receptor (ETBR) protein expression. However, it is not known if ETBR protein expression changes with aging in men. The purpose of this study was to test the hypothesis that ETBR protein expression is attenuated in older men (OM) compared with younger men (YM). Primary endothelial cells were harvested from the antecubital vein of 14 OM (60 ± 6 yr; 26 ± 3 kg/m2) and 17 YM (24 ± 5 yr; 24 ± 2 kg/m2). Cells were stained with 4′,6-diamidino-2-phenylindole, vascular endothelial cadherin, and ETBR. Images were quantified using immunocytochemistry. Endothelial function was assessed using brachial artery flow-mediated dilation (FMD). Systolic BP was similar (OM, 123 ± 11 vs. YM, 122 ± 10 mmHg) whereas diastolic BP was higher in OM (OM, 77 ± 7 vs. YM, 70 ± 6 mmHg; P < 0.01). Total testosterone was lower in OM (OM, 6.28 ± 4.21 vs. YM, 9.10 ± 2.68 ng/mL; P = 0.03). As expected, FMD was lower in OM (OM, 3.85 ± 1.51 vs. YM, 6.40 ± 2.68%; P < 0.01). However, ETBR protein expression was similar between OM and YM (OM, 0.39 ± 0.17 vs. YM, 0.42 ± 0.17 AU; P = 0.66). These data suggest that ETBR protein expression is not altered with age in men. These findings contrast with our previous data in women and further support sex differences in the endothelin system. NEW & NOTEWORTHY Our laboratory has previously shown that age-related declines in endothelial function are associated with a reduction in endothelial cell ETBR protein expression in women. However, it is unclear if endothelial cell ETBR protein expression is reduced with aging in men. This study demonstrates that endothelial cell ETBR protein expression is preserved with aging in men, and provides additional evidence for sex differences in the endothelin system.Item Evidence of reduced peripheral microvascular function in young Black women across the menstrual cycle(Journal of Applied Physiology, 2021-12-01) D’Agata, Michele N.; Hoopes, Elissa K.; Berube, Felicia R.; Hirt, Alexandra E.; Kuczmarski, Andrew V.; Ranadive, Sushant M.; Wenner, Megan M.; Witman, Melissa A.Black women (BLW) have a higher prevalence of cardiovascular disease (CVD) morbidity and mortality compared with White women (WHW). A racial disparity in CVD risk has been identified early in life as young adult BLW demonstrate attenuated vascular function compared with WHW. Previous studies comparing vascular function between premenopausal WHW and BLW have been limited to the early follicular (EF) phase of the menstrual cycle, which may not reflect their vascular function during other menstrual phases. Therefore, we evaluated peripheral microvascular function in premenopausal WHW and BLW using passive leg movement (PLM) during three menstrual phases: EF, ovulation (OV), and mid-luteal (ML). We hypothesized that microvascular function would be augmented during the OV and ML phases compared with the EF phase in both groups, but would be attenuated in BLW compared with WHW at all three phases. PLM was performed on 26 apparently healthy premenopausal women not using hormonal contraceptives: 15 WHW (23 ± 3 yr), 11 BLW (24 ± 5 yr). There was a main effect of race on the overall change in leg blood flow (ΔLBF) (P = 0.01) and leg blood flow area under the curve (LBF AUC) (P = 0.02), such that LBF was lower in BLW. However, there was no effect of phase on ΔLBF (P = 0.69) or LBF AUC (P = 0.65), nor an interaction between race and phase on ΔLBF (P = 0.37) or LBF AUC (P = 0.75). Despite peripheral microvascular function being unchanged across the menstrual cycle, a racial disparity was apparent as microvascular function was attenuated in BLW compared with WHW across the menstrual cycle. NEW & NOTEWORTHY: This is the first study to compare peripheral microvascular function between young, otherwise healthy Black women and White women at multiple phases of the menstrual cycle. Our novel findings demonstrate a significant effect of race on peripheral microvascular function such that Black women exhibit significant attenuations in microvascular function across the menstrual cycle compared with White women.Item Impact of angiotensin receptor–neprilysin inhibition on vascular function in heart failure with reduced ejection fraction: A pilot study(Physiological Reports, 2022-03-05) Nathaniel, Sangeetha; McGinty, Shane; Witman, Melissa A. H.; Edwards, David G.; Farquhar, William B.; Hosmane, Vinay; Wenner, Megan M.The mechanisms for the benefits of Angiotensin Receptor Neprilysin Inhibition (ARNi) in heart failure patients with reduced ejection fraction (HFrEF) are likely beyond blood pressure reduction. Measures of vascular function such as arterial stiffness and endothelial function are strong prognostic markers of cardiovascular outcomes in HFrEF, yet the impact of ARNi on vascular health remains to be explored. We hypothesized that arterial stiffness and endothelial function would improve after 12 weeks of ARNi in HFrEF. We tested 10 stable HFrEF patients at baseline and following 12 weeks of ARNi [64 ± 9 years, Men/Women: 9/1, left ventricular ejection fraction (EF): 28 ± 6%] as well as 10 stable HFrEF patients that remained on conventional treatment (CON: 60 ± 7 years, Men/Women: 6/4, EF: 31 ± 5%; all p = NS). Arterial stiffness was assessed via carotid-femoral pulse wave velocity (PWV) and endothelial function was assessed via brachial artery flow-mediated dilation (FMD). PWV decreased after 12 weeks of ARNi (9.0 ± 2.1 vs. 7.1 ± 1.2 m/s; p < 0.01) but not in CON (7.0 ± 2.4 vs. 7.5 ± 2.3 m/s; p = 0.35), an effect that remained when controlling for reductions in mean arterial pressure (p < 0.01). FMD increased after 12 weeks of ARNi (2.2 ± 1.9 vs. 5.5 ± 2.1%; p < 0.001) but not in CON (4.8 ± 3.8 vs. 5.4 ± 3.4%; p = 0.34). Baseline PWV (p = 0.06) and FMD (p = 0.07) were not different between groups. These preliminary data suggest that 12 weeks of ARNi therapy may reduce arterial stiffness and improve endothelial function in HFrEF. Thus, the findings from this pilot study suggest that the benefits of ARNi are beyond blood pressure reduction and include improvements in vascular function. New & Noteworthy: Twelve weeks of ARNi therapy may reduce arterial stiffness (assessed by carotid-femoral PWV) and improve endothelial function (assessed by brachial artery FMD) in HFrEF when compared to conventional treatment. Improvement in vascular function may be a physiological mechanism for the clinical benefit seen with ARNi in HFrEF. Moreover, these pleiotropic benefits of ARNi beyond BP lowering may be vital for the treatment of HFrEF and possibly other cardiovascular diseases.