Key result
Adipose-specific VEGF-A deficiency in mice significantly increased aortic collagen deposition (33.82% vs. 24.25%) and impaired acetylcholine-induced aortic relaxation.
Why the study?
Cardiovascular complications of obesity are rising, and thoracic perivascular adipose tissue releases factors influencing neighboring vascular tissue, prompting investigation into whether adipose-specific ablation of VEGF-A affects aortic structure and function.
Does adipose-specific ablation of VEGF-A impair aortic structure and function in mice?
Does adipose-specific ablation of VEGF-A impair aortic structure and function in mice?
Absolute Event Rate: 33.82% vs 24.25%
p-value: p=<0.05
Adipose-specific VEGF-A deficiency in perivascular adipose tissue leads to impaired aortic relaxation and increased collagen deposition, suggesting a critical role for PVAT angiogenesis in maintaining macrovascular function.
Objective. Thoracic perivascular adipose tissue (PVAT) has been shown to release factors which 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 ratio metric 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 thoracic aorta has a detrimental effect on aortic integrity and vascular function. Modulation of angiogenic pathways within PVAT may offer an important avenue towards the treatment of adipose tissue dysfunction in obesity and its vascular complications.
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Gharakhanian et al. (2019) studied Vascular dysfunction (n=12). Adipose-specific VEGF-A ablation vs. Fabp4cre(-) VEGFflox/flox (control) was evaluated on Collagen deposition within the aortic media and adventitia (p=<0.05). Adipose-specific VEGF-A deficiency in mice significantly increased aortic collagen deposition (33.82% vs. 24.25%) and impaired acetylcholine-induced aortic relaxation.
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