Jazzar Ashley, Jacques Danielle, Abou-Aichi Amira, Bkaily Ghassan
Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Pathophysiology. 2025 Mar 13;32(1):12. doi: 10.3390/pathophysiology32010012.
Elevated circulating insulin levels between 80 and 100 µU/mL characterize hyperinsulinemia, which often leads to metabolic disorders such as obesity, insulin resistance, and type 2 diabetes (T2D). Elevated circulating insulin levels can directly affect vascular function and contribute to the pathophysiology of the cardiovascular system, including secondary arterial hypertension (SAH) and atherosclerosis. It is well known that hyperinsulinemia induced remodeling of the heart. However, there is no information on whether intrinsic differences exist between human vascular smooth muscle cells (VSMCs) and if in vitro mimicking hyperinsulinemia induces human VSMCs morphological and intracellular homeostasis remodeling in a sex- and sex hormones-dependent manner. Our in vitro cultured human VSMCs, coupled with quantitative 3D confocal imaging results, show that intrinsic differences exist between VSMCs from young men and women. Chronic hyperinsulinemia (80 µU/mL, 48 h treatment) increases cell and nuclear volumes associated with increased intracellular calcium (Ca) and ROS and decreased glutathione. In the absence of hyperinsulinemia, pretreatment with testosterone in VSMCs from men and oestradiol in VSMCs from women had no effect. Both sex hormones partially but not completely prevented hyperinsulinemia-induced remodeling of VSMCs from young men and women. The increase in VSMC volume may increase the thickness of the tunica media, leading to a decrease in the lumen of the blood vessel, which promotes the development of SAH and atherosclerosis in a sex-dependent manner.
循环胰岛素水平在80至100 µU/mL之间升高是高胰岛素血症的特征，高胰岛素血症常导致肥胖、胰岛素抵抗和2型糖尿病（T2D）等代谢紊乱。循环胰岛素水平升高可直接影响血管功能，并促成心血管系统的病理生理学变化，包括继发性动脉高血压（SAH）和动脉粥样硬化。众所周知，高胰岛素血症会导致心脏重塑。然而，关于人类血管平滑肌细胞（VSMC）之间是否存在内在差异，以及体外模拟高胰岛素血症是否会以性别和性激素依赖的方式诱导人类VSMC形态和细胞内稳态重塑，目前尚无相关信息。我们体外培养的人类VSMC，结合定量3D共聚焦成像结果，表明年轻男性和女性的VSMC之间存在内在差异。慢性高胰岛素血症（80 µU/mL，处理48小时）会增加细胞和细胞核体积，同时细胞内钙（Ca）和活性氧（ROS）增加，谷胱甘肽减少。在不存在高胰岛素血症的情况下，男性VSMC用睾酮预处理和女性VSMC用雌二醇预处理均无效果。两种性激素都部分但未完全阻止高胰岛素血症诱导的年轻男性和女性VSMC重塑。VSMC体积增加可能会增加中膜厚度，导致血管腔减小，从而以性别依赖的方式促进SAH和动脉粥样硬化的发展。
