Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.
Function (Oxf). 2022 Dec 9;4(2):zqac063. doi: 10.1093/function/zqac063. eCollection 2023.
Arteries and veins are lined by nonproliferating endothelial cells that play a critical role in regulating blood flow. Endothelial cells also regulate tissue perfusion, metabolite exchange, and thrombosis. It is thought that endothelial cells rely on ATP generated via glycolysis, rather than mitochondrial oxidative phosphorylation, to fuel each of these energy-demanding processes. However, endothelial metabolism has mainly been studied in the context of proliferative cells, and little is known about energy production in endothelial cells within the fully formed vascular wall. Using intact arteries isolated from rats and mice, we show that inhibiting mitochondrial respiration disrupts endothelial control of vascular tone. Basal, mechanically activated, and agonist-evoked calcium activity in intact artery endothelial cells are each prevented by inhibiting mitochondrial ATP synthesis. Agonist-evoked calcium activity was also inhibited by blocking the transport of pyruvate, the master fuel for mitochondrial energy production, through the mitochondrial pyruvate carrier. The role for mitochondria in endothelial cell energy production is independent of species, sex, or vascular bed. These data show that a mitochondrial ATP supply is necessary for calcium-dependent, nitric oxide-mediated endothelial control of vascular tone, and identifies the critical role of endothelial mitochondrial energy production in fueling perfused blood vessel function.
动脉和静脉由非增殖性内皮细胞排列而成，这些细胞在调节血流方面起着至关重要的作用。内皮细胞还调节组织灌注、代谢物交换和血栓形成。人们认为，内皮细胞依赖于糖酵解产生的 ATP，而不是线粒体氧化磷酸化，来为这些能量需求高的过程提供燃料。然而，内皮细胞代谢主要在增殖细胞的背景下进行研究，对于完全形成的血管壁中内皮细胞的能量产生知之甚少。我们使用从大鼠和小鼠中分离的完整动脉，结果表明，抑制线粒体呼吸会破坏内皮细胞对血管张力的控制。完整动脉内皮细胞的基础、机械激活和激动剂诱导的钙活性均因抑制线粒体 ATP 合成而受到抑制。通过阻断线粒体丙酮酸载体运输线粒体能量产生的主要燃料丙酮酸，也抑制了激动剂诱导的钙活性。线粒体在内皮细胞能量产生中的作用与物种、性别或血管床无关。这些数据表明，线粒体 ATP 供应对于钙依赖性、一氧化氮介导的内皮细胞对血管张力的控制是必要的，并且确定了内皮线粒体能量产生在为充满血液的血管功能提供燃料方面的关键作用。
