Human Perivascular Adipose Tissue Contains an Adrenergic System

Abstract

Perivascular adipose tissue (PVAT), fat tissue that wraps most blood vessels of the body, can alter vascular tone through various mechanisms. Our team discovered a source of a releasable pool of catecholamines in PVAT from the rat but the relevance to human physiology is unknown. Increased adipose tissue mass is observed in obesity. Sympathetic activity is also increased in obesity‐associated hypertension. Thus, the link between obesity and hypertension could be the PVAT adrenergic system. PVAT may affect vascular tone negatively in disease leading to hypertensive states. We hypothesized that similar to the rat, human PVAT would contain an adrenergic system that could synthesize and store catecholamines. Tissue was collected from patients (body mass index= 43.58±3.23, age range 29–58; mean age= 41.56±3.62, 8 females and 1 male) during elective bariatric surgery and placed into physiological saline solution (PSS). Splanchnic blood vessels with associated PVAT were dissected from the tissue and snap frozen for HPLC analysis or saved for immununohistochemistry (IHC). Dopamine (DA) and norepinephrine (NE) were quantified by HPLC in human mesenteric artery PVAT. NE was the most abundant catecholamine with concentrations of 14.63±1.39 ng/g NE vs. 0.80±0.09 ng/g DA (N=9). Two key enzymes in catecholamine synthesis; tyrosine hydroxylase and dopamine β‐hydroxylase, were located to PVAT adipocytes by IHC (N=9). In order for catecholamines to be released, a storage reservoir that holds catecholamines may be present in PVAT. IHC for the vesicular monoamine transporter 2 (VMAT2) indicated the presence of the transporter in the adipocyte cytoplasm (N=9). Negative controls were performed without the inclusion of the primary antibody and these were not positive. These data indicate that human PVAT contains elements of an adrenergic system complete with capabilities of synthesis and storage of catecholamines. Sympathetic activity of an adrenergic system located within PVAT may effect vascular tone in a balance that could be altered in disease to promote contraction. Future studies aimed to understand the differences in the PVAT adrenergic system of obese hypertensives compared to obese non‐hypertensives are necessary to address the question as to why a subset and not all obese people develop hypertension.Support or Funding InformationNIH NHLBI P01HL70687IPSTP 5 T32 GM 92715‐4NIH NRSA F31 HL128035‐01