Reactive oxygen species (ROS) are implicated in cardiovascular and neurologic disorders including atherosclerosis, heart attack, stroke, and traumatic brain injury. Whereas oxidative stress can lead to apoptosis of vascular cells, such findings are largely based upon isolated vascular smooth muscle cells (SMCs) and endothelial cells (ECs) studied in culture. Studying intact resistance arteries, we have focused on understanding how SMCs and ECs in the blood vessel wall respond to acute oxidative stress induced by hydrogen peroxide, a ubiquitous, membrane-permeant ROS. We find that apoptosis induced by H₂O₂ is far greater in SMCs compared to ECs. For both cell types, apoptosis is associated with a rise in intracellular calcium concentration ([Ca²⁺]_i) during H₂O₂ exposure. Consistent with their greater death, the rise in [Ca²⁺]_i for SMCs exceeds that in ECs. Finding that disruption of the endothelium increases SMC death, we address how myoendothelial coupling and paracrine signaling attenuate apoptosis. Remarkably, conditions associated with chronic oxidative stress (advanced age, western-style diet) protect SMCs during H₂O₂ exposure, as does female sex. In light of intracellular Ca²⁺ handling, we consider how glycolytic vs. oxidative pathways for ATP production and changes in mitochondrial structure and function impact cellular resilience to H₂O₂-induced apoptosis. Gaining new insight into protective signaling within and between SMCs and ECs of the arterial wall can be applied to promote vascular cell survival (and recovery of blood flow) in tissues subjected to acute oxidative stress as occurs during reperfusion following myocardial infarction and thrombotic stroke.

中文翻译：

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过氧化氢诱导的阻力动脉细胞凋亡：内皮与平滑肌相比具有更大的弹性

活性氧 (ROS) 与心血管和神经系统疾病有关，包括动脉粥样硬化、心脏病发作、中风和创伤性脑损伤。尽管氧化应激可导致血管细胞凋亡，但这些发现主要基于在培养中研究的分离的血管平滑肌细胞 (SMC) 和内皮细胞 (EC)。通过研究完整的阻力动脉，我们专注于了解血管壁中的 SMC 和 EC 如何对过氧化氢（一种普遍存在的膜渗透性 ROS）诱导的急性氧化应激作出反应。_{我们发现，与 ECs 相比，H 2} O ₂在 SMCs中诱导的细胞凋亡要大得多。对于这两种细胞类型，细胞凋亡都与细胞内钙浓度（[Ca ²⁺ ]_i ) 在 H ₂ O ₂暴露期间。^{与他们更大的死亡相一致，SMCs [Ca 2+} ] _i的上升超过了 ECs。发现内皮的破坏会增加 SMC 死亡，我们解决了肌内皮耦合和旁分泌信号如何减弱细胞凋亡。值得注意的是，与慢性氧化应激相关的疾病（高龄、西式饮食）在 H ₂ O ₂暴露期间可保护 SMC，女性也一样。鉴于细胞内 Ca ²⁺处理，我们考虑了 ATP 产生的糖酵解与氧化途径以及线粒体结构和功能的变化如何影响细胞对 H ₂ O _{2的恢复力}-诱导的细胞凋亡。获得对动脉壁 SMC 和 EC 内部和之间的保护性信号传导的新见解，可用于促进遭受急性氧化应激的组织中的血管细胞存活（和血流恢复），如心肌梗塞和血栓性中风后再灌注期间发生的那样。