1. α4β7 Integrin (LPAM-1) is Upregulated at Atherosclerotic Lesions and is Involved in Atherosclerosis Progression.
- Author
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Zhi, Kangkang, Li, Mengfan, Zhang, Xiaoping, Gao, Zhiwei, Bai, Jun, Wu, Yongfa, Zhou, Sili, Li, Maoquan, and Qu, Lefeng
- Subjects
INTEGRINS ,ATHEROSCLEROSIS ,LYMPHOCYTES ,CELL migration ,CELL adhesion ,LIGANDS (Biochemistry) ,IMMUNOHISTOCHEMISTRY ,IMMUNOFLUORESCENCE - Abstract
Background/Aims: Integrin activation and lymphocyte migration to the vascular intima is a key event in early atherosclerosis. α4β7 integrin (LPAM-1) and its ligand, mucosal addressin cell adhesion molecule (MAdCAM-1) are known to play an important role in homing of activated lymphocytes to gut-associated lymphoid tissues. However, it is unclear whether α4β7 integrin is involved in the pathogenesis of atherosclerosis. Methods: The expressions of α4β7 integrin and its ligands in atherosclerosis plaques from 12 week high fat diet (HFD) fed ApoE
-/- and C57BL/6 mice were examined using immunofluorescent and immunohistochemical assays, respectively. We also generated ApoE/β7 double deficient mice and compared atherosclerotic lesion development in β7+/+ ApoE-/- and β7-/- ApoE-/- mice that were fed with HFD for 12 weeks. Results: We found an upregulation of α4β7 integrin and its ligands VCAM-1 and MAdCAM-1 at atherosclerosis plaques in Apolipoprotein E deficient (ApoE-/- ) mice fed with HFD for 12 weeks. Over the 12 week HFD period, peripheral blood lymphocyte (PBL) expression of α4β7 integrin increased in parallel with aortic lesion size. A removal of α4β7 integrin by genetic deletion of the β7 chain in the ApoE-/- mouse resulted in a markedly decreased 12 week-HFD atherosclerotic plaque area. β7-/- ApoE-/- macrophages showed reduced acetylated and native LDL uptake and phagocytic activity, revealing possible roles for α4β7 at two distinct stages of macrophage dysfunction during atherogenesis. Finally, a reduced activity of integrin downstream signalling components focal adhesion kinase (FAK) and MAPK/ERK1/2 in macrophage indicates their possible engagement during α4β7 integrin signalling in atherosclerosis. Conclusions: Together our results reveal a critical role of α4β7 in diet-induced atherosclerosis in mouse. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]- Published
- 2014
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