Gharakhanian Raffi, Su Shi, Aprahamian Tamar
Division of Graduate Medical Sciences, Boston University School of Medicine, Boston, MA, United States.
Renal Section, Department of Medicine, Boston University School of Medicine, Boston, MA, United States.
Front Physiol. 2019 Jun 14;10:687. doi: 10.3389/fphys.2019.00687. eCollection 2019.
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. Adipose-specific VEGF-A-deficient mice were previously generated. Fabp4cre(+). VEGF and Fabp4cre(-). VEGF 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. PVAT-specific adiponectin expression was decreased in Fabp4cre(+). VEGF mice. Isometric tension measurements revealed a dose-dependent dysfunction in response to acetylcholine within the distal aortic segment of Fabp4cre(+). VEGF . Fabp4cre(+). VEGF mice exhibited increased aortic deposition of collagen within the thoracic adventitial and medial spaces. 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.
胸周血管脂肪组织（PVAT）已被证明可释放影响邻近血管组织功能的因子。肥胖的心血管并发症正在增加；因此，本研究旨在确定血管内皮生长因子-A（VEGF-A）的脂肪特异性消融是否在主动脉结构和功能的维持中起作用。先前已培育出脂肪特异性VEGF-A缺陷小鼠。将Fabp4cre(+)、VEGF和Fabp4cre(-)、VEGF小鼠维持在普通饮食状态。用实时定量PCR测量PVAT基因表达。用等长张力测量评估主动脉血管舒缩反应。对血管中层的胶原沉积进行组织学分析，并使用比例色素密度进行比较。在Fabp4cre(+)、VEGF小鼠中，PVAT特异性脂联素表达降低。等长张力测量显示，在Fabp4cre(+)、VEGF小鼠的远端主动脉段，对乙酰胆碱的反应存在剂量依赖性功能障碍。Fabp4cre(+)、VEGF小鼠在胸外膜和中层空间的主动脉胶原沉积增加。这些数据表明，胸主动脉周围脂肪组织微环境中VEGF-A表达的降低对主动脉完整性和血管功能有不利影响。调节PVAT内的血管生成途径可能为治疗肥胖及其血管并发症中的脂肪组织功能障碍提供一条重要途径。
