Heart and Vascular Institute, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
Shenzhen Research Institute, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
Antioxid Redox Signal. 2022 Oct;37(10-12):820-841. doi: 10.1089/ars.2021.0126. Epub 2021 Jul 23.
Shear stress and metabolic disorder are the two sides of the same atherosclerotic coin. Atherosclerotic lesions are prone to develop at branches and curvatures of arteries, which are exposed to oscillatory and low shear stress exerted by blood flow. Meanwhile, metabolic disorders are pivotal contributors to the formation and advancement of atherosclerotic plaques. Accumulated evidence has provided insight into the impact and mechanisms of biomechanical forces and metabolic disorder on atherogenesis, in association with mechanotransduction, epigenetic regulation, and so on. Moreover, recent studies have shed light on the cross talk between the two drivers of atherosclerosis. There are extensive cross talk and interactions between shear stress and metabolic disorder during the pathogenesis of atherosclerosis. The communications may amplify the proatherogenic effects through increasing oxidative stress and inflammation. Nonetheless, the precise mechanisms underlying such interactions remain to be fully elucidated as the cross talk network is considerably complex. A better understanding of the cross talk network may confer benefits for a more comprehensive clinical management of atherosclerosis. Critical mediators of the cross talk may serve as promising therapeutic targets for atherosclerotic vascular diseases, as they can inhibit effects from both sides of the plaque. Hence, further in-depth investigations with advanced omics approaches are required to develop novel and effective therapeutic strategies against atherosclerosis. . 37, 820-841.
切应力和代谢紊乱是动脉粥样硬化的一体两面。动脉粥样硬化病变易发生于动脉分支和弯曲处，这些部位受到血流产生的振荡和低切应力的作用。同时，代谢紊乱是动脉粥样硬化斑块形成和进展的关键因素。越来越多的证据揭示了生物力学力和代谢紊乱对动脉粥样硬化形成的影响和机制，涉及机械转导、表观遗传调控等。此外，最近的研究还揭示了动脉粥样硬化两个驱动因素之间的相互作用。在动脉粥样硬化的发病机制中，切应力和代谢紊乱之间存在广泛的相互作用和交流。这种交流可以通过增加氧化应激和炎症来放大促动脉粥样硬化的作用。然而，由于相互作用网络非常复杂，这种相互作用的确切机制仍有待充分阐明。更好地了解相互作用网络可能有助于更全面地管理动脉粥样硬化。这种相互作用的关键介质可以作为动脉粥样硬化性血管疾病有前途的治疗靶点，因为它们可以抑制斑块两侧的作用。因此，需要采用先进的组学方法进行进一步的深入研究，以开发针对动脉粥样硬化的新的有效治疗策略。
