Pewowaruk Ryan J
Research Service, William S. Middleton Memorial Veterans Hospital, Madison, WI USA.
Department of Medicine Division of Cardiovascular Medicine, University of WI - Madison, Madison, WI USA.
Artery Res. 2023;29(3):94-100. doi: 10.1007/s44200-023-00037-1. Epub 2023 Jul 25.
Arteries can stiffen via different mechanisms due to the distending effects of blood pressure, the extracellular (ECM) and vascular smooth muscle cells (VSMC). This short review discusses how these simple models can be applied to the complex biomechanics of arteries to gain physiological insight into why an individual's arteries are stiff and identify new therapeutic strategies. In the Multi-Ethnic Study of Atherosclerosis, the important question of whether arteries stiffen with aging due to load-dependent or structural stiffening was investigated. Structural stiffening was consistently observed with aging, but load-dependent stiffening was highly variable. Importantly, the high load-dependent stiffness was associated with future cardiovascular disease events, but structural stiffness was not. Clinical studies in older, hypertensive adults surprisingly show that decreasing vascular smooth muscle tone can cause clinically significant increases in arterial stiffness. To understand this paradox, the author developed a model simple enough for clinical data but with biologically relevant extracellular matrix (ECM) and vascular smooth muscle cell (VSMC) stiffness parameters. The effect of VSMC tone on arterial stiffness depends on the ECM-VSMC stiffness ratio. Future research is needed to develop a framework that incorporates both the blood pressure dependence of arterial stiffness and the VSMC-ECM interaction on hemodynamics. This could result in personalized arterial stiffness treatments and improved CVD outcomes. The subtitle of this review is "Learning to De-Stiffen Arteries" because our results have so far only shown that we can acutely make arteries stiffer. We are optimistic though that the findings and the analytic techniques covered here will be one of the many steps along the path of the arterial stiffness research community learning how to de-stiffen arteries.
由于血压、细胞外基质（ECM）和血管平滑肌细胞（VSMC）的扩张作用，动脉可通过不同机制发生硬化。本简短综述讨论了如何将这些简单模型应用于动脉的复杂生物力学，以深入了解个体动脉僵硬的原因并确定新的治疗策略。在动脉粥样硬化多民族研究中，研究了动脉是否因负荷依赖性或结构硬化而随年龄增长变硬这一重要问题。随着年龄增长，结构硬化持续存在，但负荷依赖性硬化变化很大。重要的是，高负荷依赖性僵硬与未来心血管疾病事件相关，但结构僵硬则不然。对老年高血压成年人的临床研究令人惊讶地表明，降低血管平滑肌张力可导致动脉僵硬出现临床上的显著增加。为理解这一矛盾现象，作者开发了一个足够简单以适用于临床数据，但具有生物学相关细胞外基质（ECM）和血管平滑肌细胞（VSMC）刚度参数的模型。VSMC张力对动脉僵硬的影响取决于ECM-VSMC刚度比。未来需要开展研究以建立一个框架，该框架既要纳入动脉僵硬对血压的依赖性，又要纳入VSMC-ECM对血流动力学的相互作用。这可能会带来个性化的动脉僵硬治疗方法并改善心血管疾病的治疗效果。本综述的副标题是“学会让动脉软化”，因为到目前为止我们的研究结果仅表明我们可以使动脉急性变硬。不过，我们乐观地认为，此处涵盖的研究结果和分析技术将是动脉僵硬研究界学习如何使动脉软化道路上众多步骤中的一步。
