Chatzizisis Yiannis S, Coskun Ahmet Umit, Jonas Michael, Edelman Elazer R, Feldman Charles L, Stone Peter H
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
J Am Coll Cardiol. 2007 Jun 26;49(25):2379-93. doi: 10.1016/j.jacc.2007.02.059. Epub 2007 Jun 8.
Although the entire coronary tree is exposed to the atherogenic effect of the systemic risk factors, atherosclerotic lesions form at specific arterial regions, where low and oscillatory endothelial shear stress (ESS) occur. Low ESS modulates endothelial gene expression through complex mechanoreception and mechanotransduction processes, inducing an atherogenic endothelial phenotype and formation of an early atherosclerotic plaque. Each early plaque exhibits an individual natural history of progression, regression, or stabilization, which is dependent not only on the formation and progression of atherosclerosis but also on the vascular remodeling response. Although the pathophysiologic mechanisms involved in the remodeling of the atherosclerotic wall are incompletely understood, the dynamic interplay between local hemodynamic milieu, low ESS in particular, and the biology of the wall is likely to be important. In this review, we explore the molecular, cellular, and vascular processes supporting the role of low ESS in the natural history of coronary atherosclerosis and vascular remodeling and indicate likely mechanisms concerning the different natural history trajectories of individual coronary lesions. Atherosclerotic plaques associated with excessive expansive remodeling evolve to high-risk plaques, because low ESS conditions persist, thereby promoting continued local lipid accumulation, inflammation, oxidative stress, matrix breakdown, and eventually further plaque progression and excessive expansive remodeling. An enhanced understanding of the pathobiologic processes responsible for atherosclerosis and vascular remodeling might allow for early identification of a high-risk coronary plaque and thereby provide a rationale for innovative diagnostic and/or therapeutic strategies for the management of coronary patients and prevention of acute coronary syndromes.
尽管整个冠状动脉树都暴露于全身风险因素的致动脉粥样硬化作用之下，但动脉粥样硬化病变却形成于特定的动脉区域，即出现低切应力和振荡切应力的部位。低切应力通过复杂的机械感受和机械转导过程调节内皮基因表达，诱导致动脉粥样硬化的内皮表型并形成早期动脉粥样硬化斑块。每个早期斑块都呈现出进展、消退或稳定的个体自然病程，这不仅取决于动脉粥样硬化的形成和进展，还取决于血管重塑反应。尽管动脉粥样硬化壁重塑所涉及的病理生理机制尚未完全明了，但局部血流动力学环境，尤其是低切应力与血管壁生物学特性之间的动态相互作用可能很重要。在本综述中，我们探讨了支持低切应力在冠状动脉粥样硬化自然病程和血管重塑中作用的分子、细胞和血管过程，并指出了与各个冠状动脉病变不同自然病程轨迹相关的可能机制。与过度扩张性重塑相关的动脉粥样硬化斑块会演变为高危斑块，因为低切应力状态持续存在，从而促进局部脂质持续积聚、炎症、氧化应激、基质破坏，最终导致斑块进一步进展和过度扩张性重塑。对动脉粥样硬化和血管重塑相关病理生物学过程的深入了解，可能有助于早期识别高危冠状动脉斑块，从而为冠状动脉疾病患者的管理和急性冠状动脉综合征的预防提供创新诊断和/或治疗策略的理论依据。
