Greater aortic perivascular adipose tissue density is associated with aging, aortic stiffness, and central blood pressure in humans.

Abstract

Aging results in aortic perivascular adipose tissue (aPVAT)-mediated aortic stiffening in preclinical animal models to promote cardiovascular dysfunction. We hypothesized that greater human aPVAT density will be associated with aging, higher aortic stiffness, and blood pressure (BP). Fourteen apparently healthy adults (6 M/8 F, age range 20-79 yr) were recruited for this study. Aortic stiffness, assessed by carotid-femoral pulse wave velocity (cfPWV), resting aortic BP via pulse wave analysis, and aPVAT and abdominal visceral adipose tissue (VAT) density by computed tomography attenuation were acquired. aPVAT and epididymal (visceral) fat from young (4-6 mo) and old (27-29 mo) mice were used for ex vivo-conditioned media intrinsic mechanical stiffness experiments. Compared with younger adults, older adults had higher cfPWV (8.6 ± 0.4 vs. 6.2 ± 0.6 m/s, P < 0.05) and greater aPVAT attenuation (-80.2 ± 2.0 vs. -95.9 ± 1.5 HU, P < 0.05), but not VAT attenuation (P > 0.05). aPVAT-conditioned media from old mice compared with young mice increased intrinsic mechanical stiffness of the aorta (4,519 ± 510 vs. 2,325 ± 563 kPa, P < 0.05), which was not observed with epididymal fat-conditioned media from old mice (P > 0.05). aPVAT, but not VAT density, was positively associated with age (r = 0.89), cfPWV (r = 0.56), resting augmentation index normalized to heart rate 75 (AIxHR75; r = 0.67), aortic systolic BP (r = 0.58), and aortic pulse pressure (PP; r = 0.59; P < 0.05, all) and were independent of VAT density (P < 0.05, all). These data herein provide evidence for aPVAT as a novel fat depot and therapeutic target to lower aortic stiffness and future cardiovascular disease risk with aging in humans.NEW & NOTEWORTHY Aortic perivascular adipose tissue (aPVAT) promotes age-related aortic stiffening in preclinical animal models, but the relation between aPVAT density and cardiovascular function in adults is unknown. We demonstrate that aPVAT, but not abdominal visceral adipose tissue density, is positively associated with aging, aortic stiffness, and higher resting aortic blood pressure in apparently healthy adults. These findings provide novel evidence for aPVAT as a viable therapeutic target for improving cardiovascular function in humans.