Abstract
Objective: Thoracic perivascular adipose tissue (PVAT) has been shown to release factors that influence the functioning of neighboring vascular tissue. Cardiovascular complications of obesity are on the rise; therefore, this study set out to determine if adipose-specific ablation of vascular endothelial growth factor-A (VEGF-A) plays a role in the maintenance of aortic structure and function.Methods: Adipose-specific VEGF-A-deficient mice were previously generated. Fabp4cre(+). VEGFflox/flox and Fabp4cre(−). VEGFflox/flox mice were maintained on chow diet. PVAT gene expression was measured with real-time quantitative PCR. Aortic vasomotor response was assessed with isometric tension measurements. Collagen deposition was analyzed histologically in the vascular media and compared using ratiometric pigment density.Results: PVAT-specific adiponectin expression was decreased in Fabp4cre(+). VEGFflox/flox mice. Isometric tension measurements revealed a dose-dependent dysfunction in response to acetylcholine within the distal aortic segment of Fabp4cre(+). VEGFflox/flox. Fabp4cre(+). VEGFflox/flox mice exhibited increased aortic deposition of collagen within the thoracic adventitial and medial spaces.Conclusion: These data demonstrate that decreased expression of VEGF-A within the surrounding adipose tissue microenvironment of the thoracic aorta has a detrimental effect on aortic integrity and vascular function. Modulation of angiogenic pathways within PVAT may offer an important avenue toward the treatment of adipose tissue dysfunction in obesity and its vascular complications.
Highlights
Arterial stiffening is a loss of arterial elasticity, progressing with age (Bramwell and Hill, 1922; Hallock, 1934; Eliakim et al, 1971; Tounian et al, 2001; Mitchell et al, 2004; McEniery et al, 2005) and obesity (Sutton-Tyrrell et al, 2001; Safar et al, 2006), affecting a large portion of the population
It should be noted that these studies were performed on adipose tissue depots that are phenotypically similar to white adipose tissue (WAT)
We recently published that the vast majority of VEGF in adipose tissue is derived from the adipocyte precursor fraction, with minimal expression of VEGF in other cell populations
Summary
Arterial stiffening is a loss of arterial elasticity, progressing with age (Bramwell and Hill, 1922; Hallock, 1934; Eliakim et al, 1971; Tounian et al, 2001; Mitchell et al, 2004; McEniery et al, 2005) and obesity (Sutton-Tyrrell et al, 2001; Safar et al, 2006), affecting a large portion of the population. The quantity of BAT is negatively correlated with obesity and age (Yoneshiro et al, 2011); in addition, imaging studies show metabolically active BAT along the thoracic, but not the abdominal, spinal area (Cypess et al, 2015). This adipose tissue surrounding the thoracic aorta is similar to interscapular BAT in structure and gene expression pattern (Fitzgibbons et al, 2011). The detailed examination of the paracrine function of perivascular brown adipocytes is warranted and important, as it will provide novel targets to modulate cardiovascular pathologies associated with both aging and obesity
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