Farb Melissa G, Park Song-Young, Karki Shakun, Gokce Noyan
Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine.
Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine;
J Vis Exp. 2017 Sep 29(127):56079. doi: 10.3791/56079.
While obesity is closely linked to the development of metabolic and cardiovascular disease, little is known about mechanisms that govern these processes. It is hypothesized that pro-atherogenic mediators released from fat tissues particularly in association with central/visceral adiposity may promote pathogenic vascular changes locally and systemically, and the notion that cardiovascular disease may be the consequence of adipose tissue dysfunction continues to evolve. Here, we describe a unique method of videomicroscopy that involves analysis of vasodilator and vasoconstrictor responses of intact small human arterioles removed from the adipose depot of living human subjects. Videomicroscopy is used to examine functional properties of isolated microvessels in response to pharmacological or physiological stimuli using a pressured system that mimics in vivo conditions. The technique is a useful approach to gain understanding of the pathophysiology and molecular mechanisms that contribute to vascular dysfunction locally within the adipose tissue milieu. Moreover, abnormalities in the adipose tissue microvasculature have also been linked with systemic diseases. We applied this technique to examine depot-specific vascular responses in obese subjects. We assessed endothelium-dependent vasodilation to both increased flow and acetylcholine in adipose arterioles (50 - 350 µm internal diameter, 2 - 3 mm in length) isolated from two different adipose depots during bariatric surgery from the same individual. We demonstrated that arterioles from visceral fat exhibit impaired endothelium-dependent vasodilation compared to vessels isolated from the subcutaneous depot. The findings suggest that the visceral microenvironment is associated with vascular endothelial dysfunction which may be relevant to clinical observation linking increased visceral adiposity to systemic disease mechanisms. The videomicroscopy technique can be used to examine vascular phenotypes from different fat depots as well as compare findings across individuals with different degrees of obesity and metabolic dysfunction. The method can also be used to examine vascular responses longitudinally in response to clinical interventions.
虽然肥胖与代谢性疾病和心血管疾病的发生密切相关,但对于调控这些过程的机制却知之甚少。据推测,脂肪组织释放的促动脉粥样硬化介质,特别是与中心性/内脏性肥胖相关的介质,可能在局部和全身促进致病性血管变化,并且心血管疾病可能是脂肪组织功能障碍的后果这一观点也在不断发展。在此,我们描述了一种独特的视频显微镜方法,该方法涉及对从活体人类受试者脂肪库中取出的完整小型人小动脉的血管舒张和血管收缩反应进行分析。视频显微镜用于使用模拟体内条件的压力系统,检查分离的微血管对药理学或生理学刺激的功能特性。该技术是一种有助于了解脂肪组织微环境中局部血管功能障碍的病理生理学和分子机制的有用方法。此外,脂肪组织微血管的异常也与全身性疾病有关。我们应用该技术检查肥胖受试者中特定脂肪库的血管反应。我们评估了在同一肥胖症手术个体的两个不同脂肪库中分离出的脂肪小动脉(内径50 - 350 µm,长度2 - 3 mm)对流量增加和乙酰胆碱的内皮依赖性血管舒张。我们证明,与从皮下脂肪库分离的血管相比,来自内脏脂肪的小动脉表现出内皮依赖性血管舒张受损。这些发现表明,内脏微环境与血管内皮功能障碍有关,这可能与将内脏肥胖增加与全身疾病机制联系起来的临床观察结果相关。视频显微镜技术可用于检查来自不同脂肪库的血管表型,以及比较不同肥胖程度和代谢功能障碍个体的研究结果。该方法还可用于纵向检查对临床干预的血管反应。