Mohajeri Amin, Shin Song Yi, Padgham Samuel, Boland Devon J, Pittman Ratterree Dana, Blizman Jacob, Han Gang, Woodman Christopher R, Trache Andreea
Department of Kinesiology and Sport Management, Texas A&M University, College Station, TX, United States.
Department of Medical Physiology, Texas A&M University Health Science Center, Bryan, TX, United States.
Front Physiol. 2025 Jul 14;16:1593886. doi: 10.3389/fphys.2025.1593886. eCollection 2025.
Aging is an independent risk factor for cardiovascular disease. Preventing age-induced arterial dysfunction and the associated risk of cardiovascular disease remains a significant clinical challenge. Aerobic exercise, which induces a temporary increase in both blood flow and pressure in active tissue, has been shown to reduce macroscale arterial stiffening in humans. This study investigates the effects of mechanical stimuli on improving aging pathophysiology of vascular smooth muscle (VSM) cells isolated from soleus feed arteries (SFA). We hypothesized that age-induced impairment of VSM contractility can be rescued by mechanical stimulation that enhances formation of smooth muscle alpha-actin (SMα-actin) fibers and cell-matrix adhesions in aged VSM cells. functional studies were used to assess myogenic contractility of VSM in isolated SFA from young (4 months) and old (24 months) Fischer 344 rats. These data indicated that pre-treatment of isolated aged SFA with a short-duration increase in intraluminal pressure rescued contractility. The mechanical stretch-induced remodeling of the cellular architecture was assessed in VSM cells isolated from young and old SFA. To dissect the mechanisms involved, the structural and functional properties of VSM cells were assessed by using mechanical stimulation combined with fluorescence confocal microscopy. Results showed that aged VSM cells respond faster than young cells to 2D biaxial cyclic stretch by increasing actin stress fiber formation and vinculin recruitment at cell-matrix adhesions. In addition, hydrostatic pressure treatment applied to aged VSM cells plated on stiffer substrates restored actin fibers and integrin β1 recruitment. Taken together, these findings suggest that discrete VSM cell mechanical properties and their ability to adapt to external mechanical signals are key in restoring VSM contractility in aging. These results are significant because they provide a novel understanding of the mechanisms by which mechanical stimulation improves VSM contractility in aged resistance arteries. Our results provide new insights into the role of VSM in vascular aging and highlight a new direction for mitigating age-related effects via mechanical stimulation-induced VSM remodeling.
衰老 是心血管疾病的一个独立风险因素。预防年龄诱导的动脉功能障碍以及相关的心血管疾病风险仍然是一项重大的临床挑战。有氧运动可使活动组织中的血流量和压力暂时增加，已被证明可减少人类的宏观动脉僵硬。本研究调查了机械刺激对改善从比目鱼肌供血动脉（SFA）分离的血管平滑肌（VSM）细胞衰老病理生理学的影响。我们假设，通过机械刺激可以挽救年龄诱导的VSM收缩功能障碍，这种刺激可增强衰老VSM细胞中平滑肌α-肌动蛋白（SMα-肌动蛋白）纤维的形成和细胞-基质粘附。功能研究用于评估来自年轻（4个月）和年老（24个月）Fischer 344大鼠的分离SFA中VSM的肌源性收缩性。这些数据表明，对分离的老年SFA进行腔内压力短期升高的预处理可挽救收缩性。在从年轻和老年SFA分离的VSM细胞中评估了机械拉伸诱导的细胞结构重塑。为了剖析其中涉及的机制，通过机械刺激结合荧光共聚焦显微镜评估了VSM细胞的结构和功能特性。结果表明，衰老的VSM细胞通过增加肌动蛋白应力纤维形成和细胞-基质粘附处的纽蛋白募集，对比年轻细胞对二维双轴循环拉伸的反应更快。此外，对铺在更硬基质上的衰老VSM细胞施加静水压力处理可恢复肌动蛋白纤维和整合素β1募集。综上所述，这些发现表明，离散的VSM细胞机械特性及其适应外部机械信号的能力是恢复衰老VSM收缩性的关键。这些结果意义重大，因为它们为机械刺激改善老年阻力动脉中VSM收缩性的机制提供了新的理解。我们的结果为VSM在血管衰老中的作用提供了新的见解，并突出了通过机械刺激诱导的VSM重塑减轻年龄相关影响的新方向。
