Homocysteinylated Albumin Promotes Increased Monocyte-Endothelial Cell Adhesion and Up-Regulation of MCP1, Hsp60 and ADAM17

PLoS One

Alessandra F. Perna¹  Sofia Salemme²  Rosanna Capasso²  Irene Sambri²  Diego Ingrosso³  Filomena Acanfora³  Cinzia Lombardi³  Ersilia Satta³  Amelia Cimmino⁴  Donald L. Puppione⁵ 

[1] Cardiovascular Research Centre, School of Medicine, Second University of Naples, Naples, Italy;Department of Biochemistry and Biophysics “F. Cedrangolo”, School of Medicine, Second University of Naples, Naples, Italy;First Division of Nephrology, School of Medicine, Second University of Naples, Naples, Italy;Institute of Genetics and Biophysics, National Research Council, Naples, Italy;The Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, United States of America

关键词: Albumins;    Monocytes;    Endothelial cells;    Electrospray ionization mass spectrometry;    Serum albumin;    Gene expression;    Cell adhesion;    Enzyme-linked immunoassays;   

DOI  :  10.1371/journal.pone.0031388

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Rationale The cardiovascular risk factor homocysteine is mainly bound to proteins in human plasma, and it has been hypothesized that homocysteinylated proteins are important mediators of the toxic effects of hyperhomocysteinemia. It has been recently demonstrated that homocysteinylated proteins are elevated in hemodialysis patients, a high cardiovascular risk population, and that homocysteinylated albumin shows altered properties. Objective Aim of this work was to investigate the effects of homocysteinylated albumin - the circulating form of this amino acid, utilized at the concentration present in uremia - on monocyte adhesion to a human endothelial cell culture monolayer and the relevant molecular changes induced at both cell levels. Methods and Results Treated endothelial cells showed a significant increase in monocyte adhesion. Endothelial cells showed after treatment a significant, specific and time-dependent increase in ICAM1 and VCAM1. Expression profiling and real time PCR, as well as protein analysis, showed an increase in the expression of genes encoding for chemokines/cytokines regulating the adhesion process and mediators of vascular remodeling (ADAM17, MCP1, and Hsp60). The mature form of ADAM17 was also increased as well as Tnf-α released in the cell medium. At monocyte level, treatment induced up-regulation of ICAM1, MCP1 and its receptor CCR2. Conclusions Treatment with homocysteinylated albumin specifically increases monocyte adhesion to endothelial cells through up-regulation of effectors involved in vascular remodeling.

【 授权许可】

CC BY