Homocysteinylated albumin promotes increased monocyte-endothelial cell adhesion and up-regulation of MCP1, Hsp60 and ADAM17.
BACKGROUND
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.


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.
Department of Biochemistry and Biophysics "F. Cedrangolo", School of Medicine, Second University of Naples, Naples, Italy.
Rosanna
R
Capasso
Irene
I
Sambri
Amelia
A
Cimmino
Sofia
S
Salemme
Cinzia
C
Lombardi
Filomena
F
Acanfora
Ersilia
E
Satta
Donald L
DL
Puppione
Alessandra F
AF
Perna
Diego
D
Ingrosso
D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000418:Albumins / Q000737:chemistry / Q000502:physiology*; D002448:Cell Adhesion; D002460:Cell Line; D018834:Chaperonin 60 / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D006710:Homocysteine / Q000737:chemistry; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D015854:Up-Regulation
D000418:Albumins; C111835:CCL2 protein, human; D018834:Chaperonin 60; D018932:Chemokine CCL2; D006710:Homocysteine; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human