The role of impaired angiogenesis on perivascular adipose tissue and macrovascular function
Gharakhanian, Raffi Abraham
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OBJECTIVE. Only recently has hypoxia within the adipose tissue microenvironment been suggested to influence metabolic dysfunction and cardiovascular complications. Although its exact function is largely unknown, thoracic perivascular adipose tissue (PVAT) has been shown to release factors which influence vascular function. The objective of this study is to determine if vascular endothelial growth factor-A (VEGF-A) within PVAT plays a role in the maintenance of aortic structure and function. MATERIALS/METHODS. Mice with adipose-specific deficiency of VEGF were previously generated in the lab. Fabp4cre(+).VEGF^flox/flox and Fabp4cre(-).VEGF^flox/flox mice were maintained on chow diet for the entirety of this study. PVAT gene expression was measured with real time quantitative PCR. Aortic vasomotor response was assessed with isometric tension measurements. Aortic stiffness was measured in vivo by Doppler ultrasound and assessed using pulse wave velocity estimation. Collagen deposition was analyzed in the vascular adventitia and media with Masson's trichrome stain. RESULTS. PVAT specific adiponectin expression was decreased in Fabp4cre(+).VEGF^flox/flox female mice. Our isometric tension measurements revealed a dose-dependent dysfunction in response to acetylcholine within the distal aortic segment of Fabp4cre(+).VEGF^flox/flox female mice. Aortic stiffness estimation via pulse wave velocity revealed no difference in VEGF-A deficient mice. Fabp4cre(+).VEGF^flox/flox male 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 potentially detrimental effect on vascular function and structure. Modulation of angiogenic pathways within PVAT may offer an important avenue towards the treatment of adipose tissue dysfunction and prevention of related metabolic disorders and cardiovascular diseases.