Department of Exercise Physiology, West Virginia University School of Medicine, Morgantown, WV, USA.
Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA.
Exp Physiol. 2021 Jun;106(6):1343-1358. doi: 10.1113/EP089449. Epub 2021 May 14.
What is the central question of this study? Thoracic perivascular adipose tissue (tPVAT) is known to, in part, regulate aortic function: what are the effects of unpredictable chronic mild stress (UCMS) on the tPVAT regulation of aortic function and what is the role of exercise training in alleviating the potential negative actions of UCMS on tPVAT? What is the main finding and its importance? UCMS causes tPVAT to disrupt endothelium-dependent dilatation, increases inflammatory cytokine production and diminishes tPVAT-adiponectin. Exercise training proved efficacious in preventing tPVAT-mediated disruption of aortic function. The data support a tPVAT mechanism through which chronic stress negatively impacts vascular health, which adds to our knowledge of how psychological disorders might increase the risk of cardiovascular disease.
Chronic stress is a major risk for cardiovascular disease. Perivascular adipose tissue (PVAT) has been shown to regulate vascular function; however, the impact of chronic stress and the comorbidity of metabolic syndrome (MetS) on thoracic (t)PVAT is unknown. Additionally, aerobic exercise training (AET) is known to combat the pathology of MetS and chronic stress, but the role of tPVAT in these actions is also unknown. Therefore, the purpose of this study was to examine the effects of unpredictable chronic mild stress (UCMS) on the tPVAT regulation of aortic function and the preventative effect of AET. Lean (LZR) and obese (OZR) Zucker rats (16-17 weeks old) were exposed to 8 weeks of UCMS with and without treadmill exercise (AET). In LZR, UCMS impaired aortic endothelium-dependent dilatation (EDD) (assessed ex vivo by wire myography) and aortic stiffness (assessed by elastic modulus) with no change in OZR subject to UCMS. However, both LZR and OZR UCMS tPVAT impaired EDD compared to respective controls. LZR and OZR subject to UCMS had higher oxidative stress production, diminished adiponectin and impaired aortic nitric oxide levels. Divergently, UCMS induced greater inflammatory cytokine production in LZR UCMS tPVAT, but not in OZR UCMS tPVAT. AET prevented the tPVAT impairment of aortic relaxation with UCMS in LZR and OZR. Additionally, AET reduced aortic stiffness in both LZR and OZR. These beneficial effects on tPVAT regulation of the aorta are likely due to AET preservation of adiponectin, reduced oxidative stress and inflammation, and enhanced nitric oxide. UCMS impaired tPVAT-regulated aortic function in LZR, and augmented MetS-induced EDD in OZR. Conversely, AET in combination with UCMS largely preserved aortic function and the tPVAT environment, in both groups.
本研究的核心问题是什么？胸主动脉周围脂肪组织（tPVAT）已知部分调节主动脉功能：不可预测的慢性轻度应激（UCMS）对 tPVAT 调节主动脉功能有何影响，运动训练在减轻 UCMS 对 tPVAT 的潜在负面影响方面有何作用？主要发现及其重要性是什么？UCMS 导致 tPVAT 破坏内皮依赖性扩张，增加炎性细胞因子的产生，并减少 tPVAT-脂联素。运动训练在预防 tPVAT 介导的主动脉功能障碍方面被证明是有效的。数据支持通过 tPVAT 机制，慢性应激对血管健康产生负面影响，这增加了我们对心理障碍如何增加心血管疾病风险的认识。
慢性应激是心血管疾病的主要危险因素。已经表明，血管周围脂肪组织（PVAT）可调节血管功能；然而，尚不清楚慢性应激以及代谢综合征（MetS）的合并症对胸（t）PVAT 的影响。此外，有氧运动训练（AET）已知可对抗 MetS 和慢性应激的病理学，但 tPVAT 在这些作用中的作用尚不清楚。因此，本研究的目的是研究不可预测的慢性轻度应激（UCMS）对 tPVAT 调节主动脉功能的影响以及 AET 的预防作用。瘦（LZR）和肥胖（OZR） Zucker 大鼠（16-17 周龄）接受 8 周的 UCMS 加和/或跑步机运动（AET）。在 LZR 中，UCMS 损害了主动脉内皮依赖性扩张（EDD）（通过线描测功法在体评估）和主动脉僵硬度（通过弹性模量评估），但 OZR 中 UCMS 无变化。然而，与各自的对照组相比，LZR 和 OZR 的 UCMS tPVAT 均损害了 EDD。LZR 和 OZR 接受 UCMS 的 tPVAT 产生更高的氧化应激产物，减少脂联素并损害主动脉一氧化氮水平。相反，UCMS 在 LZR UCMS tPVAT 中诱导更大的炎性细胞因子产生，但在 OZR UCMS tPVAT 中则没有。AET 预防了 LZR 和 OZR 中 UCMS 引起的 tPVAT 对主动脉松弛的损害。此外，AET 降低了 LZR 和 OZR 中的主动脉僵硬度。AET 对 tPVAT 调节主动脉的这些有益作用可能是由于 AET 保留了脂联素，减少了氧化应激和炎症，并增强了一氧化氮。UCMS 损害了 LZR 的 tPVAT 调节的主动脉功能，并增强了 OZR 中 MetS 诱导的 EDD。相反，UCMS 与 AET 联合在两组中均在很大程度上保留了主动脉功能和 tPVAT 环境。
