Aortic stiffness is lower when PVAT is included: a novel ex vivo mechanics study

Abstract

Perivascular adipose tissue (PVAT) is increasingly recognized as an essential layer of the functional vasculature, being responsible for producing vasoactive substances and assisting arterial stress relaxation. Here we test the hypothesis that PVAT reduces aortic stiffness. Our model was the thoracic aorta of the male Sprague Dawley rat. Uniaxial mechanical tests for three groups of tissue were performed: aorta +PVAT (+PVAT), aorta - PVAT (-PVAT), and isolated PVAT (PVAT only). The output of the mechanical test is reported in the form of a Cauchy stress-stretch curve. This work presents a novel, physiologically relevant approach to measure mechanical stiffness ex vivo in isolated PVAT. Low-stress stiffness (), high-stress stiffness (), and the stress corresponding to a stretch of 1.2 () were measured as metrics of distensibility. The low-stress stiffness was largest in the -PVAT samples and smallest in PVAT only samples. Both the high-stress stiffness and the stress at 1.2 stretch were significantly higher in -PVAT samples when compared to +PVAT samples. Taken together these results suggest that -PVAT samples are stiffer (less distensible) both at low stress (not significant) as well as at high stress (significant) when compared to +PVAT samples. These conclusions are supported by the results of the continuum mechanics material model we also used to interpret the same experimental data. Thus, tissue stiffness is significantly lower when considering PVAT as part of the aortic wall. As such, PVAT should be considered as a target for improving vascular function in diseases with elevated aortic stiffness, including hypertension.

Connecting Aortic Stiffness to Vascular Contraction: Does Sex Matter?

“…Second, our functional studies only evaluated vascular responses to adrenergic stimulation, which means that endothelial function was not directly assessed. Third, the contributions of PVAT to arterial stiffness were disregarded in this study, but recent evidence shows that vessel stiffness is lower when PVAT is present [ 18 ]. Notwithstanding these limitations, we firmly believe that our work narrows a fundamental knowledge gap: how sex as a variable affects intrinsic media-layer stiffness in young animals.…”

“…Briefly, 2 mm endothelium-intact rings were obtained from the thoracic aorta, and mounted with a physiological preload of 15 mN/mm. Since PVAT modifies aortic stiffness [ 18 ], studies were conducted in PVAT-denuded vessels. Each myograph chamber was filled with physiological salt solution (PSS; mmol/L: 130 NaCl, 4.7 KCl, 1.18 KH 2 PO 4 , 1.18 MgSO 4 * 7H 2 O, 14.9 NaHCO 3 , 5.6 Dextrose, 1.56 CaCl 2 * H 2 O, 0.026 EDTA), which was gassed with carbogen (95% CO 2 / 5% O 2 , pH: 7.4) and kept at 37 C. Samples were allowed to equilibrate for approximately 1 h. To test for the viability of the rings, we used a high K + solution (120 mmol/L for 10 min) modified from PSS.…”

“…The most widely used technique, PWV, non-invasively derives stiffness by calculating the transit time of the CV pulse [ 17 ]. However, PWV does not provide information about the mechanistic aspects (i.e., active and passive components) leading to variations in vessel stiffness, which can be altered by changes in endothelial function, vascular smooth muscle cells (VSMCs), extracellular matrix (ECM) [ 17 ], and perivascular adipose tissue (PVAT) [ 18 ]. Atomic force microscopy (AFM) provides nanoscale resolution of the biomechanical properties of soft biological tissues, including the vasculature [ 17 , 19 ].…”

Vascular homeostasis in atherosclerosis: A holistic overview

“…Also, another intriguing and largely unexplored research question is the precise role of perivascular adipose tissue (PVAT) in vascular health and diseases, such as atherosclerosis ( 45 , 47 ). Recent evidence has implicated PVAT as the fourth layer of the blood vessel wall (the tunica adiposa), which produces adipokines and vasoactive substances (such as leptin, adiponectin, resistin, and visfatin)/cytokines/growth factors that regulate vascular tone/homeostasis ( 4 , 48 ). One study from Tang laboratory have revealed that periaortic knockdown of ribosomal protein S3A (RPS3A) in mouse PVAT impaired PVAT browning, promoted vascular inflammation and atherosclerosis development by modulating UCP-1 expression in ApoE -/- mice ( 49 ).…”

“…These findings uncover the important role of PVAT in regulating endothelial function, inflammation and atherosclerosis. Future studies including PVAT in measuring aortic wall’s mechanical behavior, such as aortic stiffness and vasorelaxation/constriction is important ( 48 ).…”