Abstract
Mechanosensitive genes regulate multiple cardiovascular pathophysiological processes and disorders; however, the role of flow-sensitive genes in atherosclerosis is still unknown. In this study, we identify LIM Zinc Finger Domain Containing 2 (LIMS2) that acts as a mechanosensitive gene downregulated by disturbed flow (d-flow) both in human endothelial cells (ECs) in vitro and in mice in vivo. Mechanistically, d-flow suppresses LIMS2 expression, which leads to endothelial inflammation by upregulating typical inflammatory factors, VCAM-1, and ICAM-1 in human ECs. The findings indicate that LIMS2, the new flow-sensitive gene, may help us to find a new insight to explain how d-flow caused endothelial inflammation and provide a new therapeutic approach for atherosclerosis in the future.
Keywords:
Atherosclerosis; biomarker; endothelial inflammation.
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Apolipoproteins E / deficiency
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Apolipoproteins E / metabolism
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Atherosclerosis / genetics
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Atherosclerosis / pathology
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Endothelial Cells / metabolism*
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Endothelial Cells / pathology*
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Gene Silencing
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Humans
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Inflammation / genetics
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Inflammation / pathology*
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Intercellular Adhesion Molecule-1 / metabolism
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LIM Domain Proteins / genetics
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LIM Domain Proteins / metabolism*
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Mechanotransduction, Cellular
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice, Inbred C57BL
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Plaque, Atherosclerotic / pathology
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Rheology*
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Stress, Mechanical*
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Up-Regulation / genetics
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Vascular Cell Adhesion Molecule-1 / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Apolipoproteins E
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LIM Domain Proteins
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LIMS2 protein, human
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Lims2 protein, mouse
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Membrane Proteins
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Vascular Cell Adhesion Molecule-1
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Intercellular Adhesion Molecule-1