Premium
Modulation of vascular endothelial cell senescence by integrin β4
Author(s) -
Sun ChunHui,
Liu Xia,
Qi Lei,
Xu JiPing,
Zhao Jing,
Zhang Yun,
Zhang ShangLi,
Miao JunYing
Publication year - 2010
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22262
Subject(s) - senescence , umbilical vein , enos , microbiology and biotechnology , integrin , biology , endothelial stem cell , cell , nitric oxide synthase , nitric oxide , immunology , in vitro , endocrinology , biochemistry
Increasing evidence has demonstrated that the senescence of vascular endothelial cells (VECs) has critical roles in the pathogenesis of vascular dysfunction. Finding important factors that regulate VEC senescence will help provide novel therapeutic strategies for vascular disorders. Previously, we found that integrin β4 was involved in VEC senescence. However, the mechanism underlying VEC senescence mediated by integrin β4 remains poorly understand. In this study, we used a mouse in vivo model and showed that the level of integrin β4 in the endothelium of mouse thoracic aorta was increased during natural aging and atherosclerosis. Furthermore, we found that H‐ras, caveolin‐1, and AP‐1 were implicated in the senescent signal pathway mediated by integrin β4 in human umbilical vein ECs (HUVECs). Knockdown of integrin β4 could attenuate HUVEC senescent features, including increased interleukin‐8 (IL‐8) release and decreased endothelial nitric oxide synthase (eNOS) and NO levels and mitochondrial membrane potential in vitro. Our findings provide new clues illustrating the mechanism of VEC senescence. Integrin β4 might be a potential target for therapy in cardiovascular diseases. J. Cell. Physiol. 225: 673–681, 2010. © 2010 Wiley‐Liss, Inc.