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KMID : 1144120150050030162
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Biomedical Engineering Letters
2015 Volume.5 No. 3 p.162 ~ p.171
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Role for SUMOylation in disturbed flow-induced atherosclerotic plaque formation
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Abe Jun-ichi
Le Nhat-Tu
Heo Kyung-Sun
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Abstract
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Although atherosclerosis is a multi-factorial disease, the focalization of atherosclerotic plaques on the vessel wall suggests that local factors such as patterns of local blood flow are critical in the progression of atherosclerosis. Blood flow creates various types of forces onto the surface of vascular endothelial cells (ECs). Among those various types of forces, fluid shear stress has a major influence on the structure and function of ECs. At the branch points and the lesser curvature of the aortic arch, blood flow is disturbed (dflow) and atherosclerotic plaques are frequently detected. At the straight parts of the arterial tree and the greater curvature of aortic arch, blood flow is steady (s-flow, high shear stress) and atherosclerotic plaques are rare. These two patterns of blood flow (d-flow and s-flow) affects EC structure and function differently. However, molecular mechanisms underline the difference remains unclear. To provide insights into this question, studies have suggested a number of theories with multiple proposed signaling pathways, and the role of post-translational modifications has emerged. Particularly, SUMOylation is highlighted based on its potentiality to regulate a wide range of cellular functions. EC dysfunction induced by SUMOylation is proposed to accelerate d-flowinduced atherosclerosis. In this review, we focus on SUMOylation and its role in regulating transcriptional networks and propose a mechanistic link between d-flow and EC dysfunction. Since a strong correlation exists between d-flow and atherosclerotic plaque formation, understanding the mechanism of d-flow-induced SUMOylation events may reveal new paths towards therapeutic interventions against EC dysfunction and atherosclerosis.
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KEYWORD
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Atherosclerosis, Disturbed flow, EC dysfunction, Steady flow, SUMOylation
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