Journal
ANTIOXIDANTS & REDOX SIGNALING
Volume 37, Issue 10-12, Pages 820-841Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2021.0126
Keywords
shear stress; metabolic disorder; cross talk; atherosclerosis
Funding
- Research Grants Council Collaborative Research Fund [C4024-16W]
- Research Grants Council General Research Fund [14112919]
- Health and Medical Research Fund [05161746]
- National Natural Science Foundation of China [91939302, 81561128017]
- Research Grants Council Senior Research Fellow Scheme [2021-4S04]
- Hong Kong PhD Fellowship
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Shear stress and metabolic disorder play crucial roles in the pathogenesis of atherosclerosis, with complex interactions between them potentially amplifying the proatherogenic effects through increased oxidative stress and inflammation. A deeper understanding of the cross talk network holds promise for comprehensive clinical management of atherosclerosis and the development of novel therapeutic strategies.
Significance: 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. Recent Advances: 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. Critical Issues: 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. Future Directions: 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.
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