Delineating Mechanisms of Impaired Vasoreactivity in Thermoneutrality

心血管疾病(CVD)对退伍军人的健康具有毁灭性的影响，是导致 入院治疗和死亡。CVD的早期病理特征是血管反应性受损(收缩 和扩张)。因为血管系统起着分配营养和调节血液的重要作用 压力，重要的是要针对血管的早期功能障碍，以进一步了解和预防这种情况 慢性病理学。我们最近将大鼠安置在中温(TN)条件下，观察到大鼠虚弱 女性的血管反应性和高血压，导致了一种非常适合进一步研究的动物模型 脑血管病变的调查及病理性别差异。考虑血管周围脂肪组织(PVAT) 棕色脂肪组织(BAT)，包围和调节血管系统。PVAT的改建，或者是 从BAT到白色脂肪组织(WAT)的PVAT表型，可能导致PVAT旁分泌功能障碍 向飞船发出信号。在初步研究中，我们将大鼠安置在室温(RT)或TN下，并 调查它们自己的PVAT或来自相反居所的动物的PVAT以及每只大鼠自己的动脉 非原位血管反应性。在用PVAT分析TN寄养动物的主动脉中， 血管表现出显著的血管扩张能力，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诱导的减弱的扩张。我们假设 PVAT美白导致血管系统旁分泌信号机制减弱，导致 血管反应性受损。此外，性别作为一个生物变量决定了弱化的病理。 PVAT和血管系统串扰。我们将确定血管组织功能障碍是否由 与PVAT美白相关的PVAT旁分泌信号改变，确定雌激素对PVAT的影响 白化和血管功能障碍，并阐明PVAT重塑是否驱动改变的β-肾上腺素能- 对温度的诱导反应。支持这些目标的实验结果不仅将产生新的数据 TN诱导的PVAT对雌雄大鼠血管系统和线粒体代谢的调节 明确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.