Role of Hic-5 in the formation of microvilli-like structures and the monocyte–endothelial interaction that accelerates atherosclerosis. (13th January 2015)

• Record Type: Journal Article
• Authors: Arita-Okubo, Shigeko; Kim-Kaneyama, Joo-ri; Lei, Xiao-Feng; Fu, Wen-Guang; Ohnishi, Koji; Takeya, Motohiro; Miyauchi, Aya; Honda, Hirokazu; Itabe, Hiroyuki; Miyazaki, Takuro; Miyazaki, Akira
• Is Part Of: Cardiovascular research. Volume 105:Number 3(2015)
• Page Start: 361
• Page End: 371
• Publication Date: 2015-01-13
• Subjects: Atherosclerosis -- Microvilli-like structures -- Endothelial cells; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Periodicals; 616.1
• DOI: 10.1093/cvr/cvv003
• Languages: English
• ISSNs: 0008-6363

Abstract

Abstract: Aims: The adhesion of circulating monocytes to endothelial cells (ECs) is an early and critical event in the formation of atherosclerotic plaques. Hydrogen peroxide-inducible clone 5 (Hic-5) serves as an adaptor molecule in cell adhesion complexes. However, the role of endothelial Hic-5 in monocyte–EC interaction and atherogenesis remains unclear. We examined the roles of endothelial Hic-5 in monocyte–EC interaction and atherogenesis using mouse models of atherosclerosis and cultured human umbilical vein endothelial cells (HUVECs). Methods and results: Hic-5 was expressed in ECs, but not in monocytes/macrophages. An ex vivo monocyte adhesion assay revealed that adhesion of THP-1 monocytes to aortas isolated from Apoe −/− and LDLR −/− mice stimulated by TNF-α or oxidized LDL was suppressed by Hic-5 deficiency. Scanning electron microscopic observations of aortas harvested from Apoe −/− mice revealed that TNF-α- or oxidized LDL-induced microvilli-like structures were markedly suppressed by Hic-5 deficiency. Relative Hic-5 deficiency suppressed 60% of the atherosclerotic lesions in aortas from Apoe −/− and LDLR −/− mice. In contrast, overexpression of Hic-5 in HUVECs promoted induction of microvilli-like structures and adherence of THP-1 cells in an adhesion receptor such as intercellular adhesion molecule-1- and vascular cell adhesion molecule-1-dependent manner. Conclusion: Hic-5 in ECs plays an important role in the formation of microvilli-like structures and in the interaction between ECs and monocytes, leading to monocyte recruitment and subsequent development of atherosclerosis.