Taylor Mark S, Lowery Jordan, Choi Chung-Sik, Francis Michael
Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile, AL, United States.
Department of Pathology, University of South Alabama College of Medicine, Mobile, AL, United States.
Front Physiol. 2022 Mar 22;13:848681. doi: 10.3389/fphys.2022.848681. eCollection 2022.
Endothelial dysfunction is a key feature of cardiovascular disease (CVD) including atherosclerosis. Impaired endothelial signaling leads to plaque formation, vascular wall remodeling and widespread cardiovascular dysregulation. The specific changes along the vascular intima associated with atherosclerosis, including the vulnerable circulation downstream of the flow obstruction, remain poorly understood. Previous findings from animal models suggest that preservation of a distinct Ca signaling profile along the arterial endothelial network is crucial for maintaining vasculature homeostasis and preventing arterial disease. Ca signaling in the intact human artery intima has not been well characterized. Here, we employed confocal imaging and a custom analysis algorithm to assess the spatially and temporally dynamic Ca signaling profiles of human peripheral arteries isolated from the amputated legs of patients with advanced CVD (peripheral artery disease and/or diabetes) or patients who had lost limbs due to non-cardiovascular trauma. In all tibial artery branches (0.5-5 mm diameter) assessed, the intima consistently elicited a broad range of basal Ca signals ranging from isolated focal transients to broad waves. Arteries from patients with existing CVD displayed a restricted intimal Ca signaling pattern characterized by diminished event amplitude and area. Stimulation of type-4 vanilloid transient receptor potential channels (TRPV4) amplified endothelial Ca signals; however, these signals remained smaller and spatially confined in arteries from patients with CVD verses those without CVD. Our findings reveal a characteristic underlying basal Ca signaling pattern within the intima of human peripheral arteries and suggest a distinct truncation of the inherent Ca profile with CVD.
内皮功能障碍是包括动脉粥样硬化在内的心血管疾病（CVD）的关键特征。内皮信号传导受损会导致斑块形成、血管壁重塑和广泛的心血管调节异常。与动脉粥样硬化相关的血管内膜的具体变化，包括血流阻塞下游的易损循环，仍知之甚少。此前动物模型的研究结果表明，沿动脉内皮网络保留独特的钙信号特征对于维持血管系统稳态和预防动脉疾病至关重要。完整人类动脉内膜中的钙信号尚未得到很好的表征。在此，我们采用共聚焦成像和定制分析算法，以评估从患有晚期CVD（外周动脉疾病和/或糖尿病）的患者或因非心血管创伤而截肢的患者的截肢腿部分离出的人类外周动脉的时空动态钙信号特征。在所有评估的胫动脉分支（直径0.5 - 5毫米）中，内膜持续引发广泛的基础钙信号，范围从孤立的局灶性瞬变到广泛的波。患有现有CVD的患者的动脉显示出一种受限的内膜钙信号模式，其特征为事件幅度和面积减小。对4型香草酸瞬时受体电位通道（TRPV4）的刺激放大了内皮钙信号；然而，与没有CVD的患者的动脉相比，这些信号在患有CVD的患者的动脉中仍然较小且在空间上受限。我们的研究结果揭示了人类外周动脉内膜内潜在的特征性基础钙信号模式，并表明CVD会使固有钙信号特征明显截断。
