Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
J Smooth Muscle Res. 2021;57(0):94-107. doi: 10.1540/jsmr.57.94.
Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are major cell types that control vascular function, and hence dysfunction of these cells plays a key role in the development and progression of vasculopathies. Abnormal vascular responsiveness to vasoactive substances including vasoconstrictors and vasodilators has been observed in various arteries in diseases including diabetes, hypertension, chronic kidney diseases, and atherosclerosis. Several substances derived from ECs tightly control vascular function, such as endothelium-derived relaxing and contracting factors, and it is known that abnormal vascular signaling of these endothelium-derived substances is often observed in various diseases. Derangement of signaling in VSMCs and altered function influence vascular reactivity to vasoactive substances and tone, which are important determinants of vascular resistance and blood pressure. However, understanding the molecular mechanisms underlying abnormalities of vascular functions in pathological states is difficult because multiple substances interact in the development of these processes. Advanced glycation end products (AGEs), a heterogeneous group of bioactive compounds, are thought to contribute to vascular dysfunction, which in turn cause the development of several diseases including diabetes, hypertension, stroke, and atherosclerosis. A growing body of evidence suggests that AGEs could affect these cells and modulate vascular function. This study is focused on the link between AGEs and functions of ECs and VSMCs, particularly the modulative effects of AGEs on vascular reactivities to vasoactive substances.
血管平滑肌细胞 (VSMCs) 和内皮细胞 (ECs) 是控制血管功能的主要细胞类型，因此这些细胞的功能障碍在血管病变的发生和发展中起着关键作用。在包括糖尿病、高血压、慢性肾脏病和动脉粥样硬化在内的各种疾病中，已经观察到各种动脉对包括血管收缩剂和血管扩张剂在内的血管活性物质的血管反应异常。一些源自 ECs 的物质可以紧密控制血管功能，例如内皮衍生的舒张和收缩因子，并且已知这些内皮衍生物质的异常血管信号在各种疾病中经常观察到。VSMCs 中的信号转导紊乱和功能改变会影响血管对血管活性物质和张力的反应性，这是血管阻力和血压的重要决定因素。然而，由于在这些过程的发展中多种物质相互作用，因此理解病理状态下血管功能异常的分子机制是困难的。晚期糖基化终产物 (AGEs) 是一组异质的生物活性化合物，被认为有助于血管功能障碍，进而导致包括糖尿病、高血压、中风和动脉粥样硬化在内的几种疾病的发生。越来越多的证据表明，AGEs 可能会影响这些细胞并调节血管功能。本研究重点关注 AGEs 与 ECs 和 VSMCs 功能之间的联系，特别是 AGEs 对血管活性物质血管反应性的调节作用。
