Delineating Mechanisms of Impaired Vasoreactivity in Thermoneutrality

心血管疾病（CVD）对退伍军人的健康有着毁灭性的影响，是导致 住院和死亡。CVD的早期病理学特征为血管反应性受损（收缩 和膨胀）。由于脉管系统具有分配营养和调节血液的关键功能， 因此，重要的是要针对血管中的早期功能障碍，以进一步了解和预防这种情况。 慢性病理学我们最近将大鼠置于热中性（TN）条件下， 血管反应性沿着女性高血压，导致非常适合进一步研究的动物模型。 脑血管病的调查沿着有性别病理差异。血管周围脂肪组织（PVAT），考虑 棕色脂肪组织（BAT）围绕并调节脉管系统。PVAT的重塑，或 PVAT表型从BAT转变为白色脂肪组织（WAT），可能导致PVAT的旁分泌功能障碍 向船只发出信号。在初步研究中，我们将大鼠饲养在室温（RT）或TN下， 研究了它们自己的PVAT或来自相反圈养的动物的PVAT沿着每只大鼠自己的主动脉， 血管反应性异位。在用RT圈养动物的PVAT分析的TN圈养动物的主动脉中， 血管显示血管舒张能力显著增加，强烈表明PVAT不仅 调节血管反应性，但可以修复持续观察到的TN诱导的扩张减弱。我们假设 PVAT变白导致血管系统的旁分泌信号机制减少， 血管反应性受损此外，性别作为一个生物学变量决定了病理减少 PVAT和脉管系统串扰。我们将确定血管组织的功能障碍是否由 改变PVAT旁分泌信号与PVAT美白，定义雌激素对PVAT的影响 白化和血管功能障碍，并阐明PVAT重塑是否驱动改变β-肾上腺素能- 诱导对温度的反应。支持这些目标的实验结果不仅会产生新的数据， 对TN诱导的PVAT调节雌性和雄性大鼠的血管和线粒体代谢的影响，而且 查明所有患有心血管疾病的退伍军人血管功能受损治疗方式的性别差异。

Cardiovascular disease (CVD) has a devastating impact on Veteran health and is a leading cause of both hospitalization and death. Early pathology of CVD is characterized by impaired vasoreactivity (constriction and dilation). As the vasculature serves the critical functions of distributing nutrients and regulating blood pressure, it is important to target early dysfunction in the vascular to further understand and prevent this chronic pathology. We recently housed rats at thermoneutral (TN) conditions and observed debilitated vasoreactivity along with high blood pressure in females, resulting in an animal model well-suited to further CVD investigation along with sex differences in pathology. Perivascular adipose tissue (PVAT), considered brown adipose tissue (BAT), surrounds and regulates the vasculature. Remodeling of PVAT, or the change in PVAT phenotype from BAT to white adipose tissue (WAT), may cause dysfunction in PVAT’s paracrine signaling to the vessel. In a preliminary study, we housed rats at either room temperature (RT) or TN and investigated their own PVAT or PVAT from the oppositely- housed animals along with each rat’s own aorta for vasoreactivity ex situ. In aorta of TN-housed animals analyzed with PVAT from RT-housed animals, the vessels showed a significant increase in vasodilation capacity, strongly suggesting that PVAT not only regulates vasoreactivity, but can repair consistently observed TN-induced diminished dilation. We hypothesize that PVAT whitening results in diminished paracrine signaling mechanisms to the vasculature, causing damaged vasoreactivity. Furthermore, sex as a biological variable determines the pathology of diminished PVAT and vasculature crosstalk. We will determine whether dysfunction in vascular tissue is governed by altered PVAT paracrine signaling associated with PVAT whitening, define the impact of estrogen on PVAT whitening and vascular dysfunction, and elucidate whether PVAT remodeling drives altered β-adrenergic- induced response to temperature. Experimental results supporting these aims will not only generate novel data on TN-induced PVAT regulation of vasculature and mitochondrial metabolism in female and male rats, but also pinpoint sex differences in treatment modalities for impaired vascular function in all Veterans with CVD.