Mechanisms of c-reactive protein up-regulation in arterialized vein grafts.
BACKGROUND
C-reactive protein (CRP), an acute phase reactant, is an independent predictor of coronary artery syndromes and a mediator of the vascular response to injury. CRP has been found in arterialized vein grafts and has been linked to atherogenesis; however, its involvement in vein graft early failure or intimal hyperplasia has not been assessed. This study was designed to investigate the mechanism(s) of CRP up-regulation in arterialized vein grafts.


METHODS
Carotid artery bypass with arterialized jugular vein grafts (AVG) was performed in 18 dogs. AVG were harvested at 3, 8, and 24 hours and 4, 14, and 28 days, using the femoral vein obtained at the time of AVG harvest as a control. Serum CRP levels were characterized by enzyme-linked immunosorbent assay; AVG expression of CRP was studied by immunofluorescence, Western blotting, in situ hybridization, Northern blotting, and quantitative RT-PCR.


RESULTS
CRP levels peaked at 24 hours in serum and AVG but remained at baseline in control veins. By double immunofluorescence, CRP was associated with the media and adventitia of AVG. However, Northern blotting analysis showed no CRP mRNA expression in AVG. Reverse transcriptase polymerase chain reaction analysis confirmed the lack of up-regulation of CRP in AVG.


CONCLUSIONS
CRP levels are increased in AVG, peaking 24 hours after arterialization. However, no significant production of CRP was detected in AVG. Therefore, increased CRP levels within AVG appear to originate mostly from CRP diffusion from the systemic circulation. These results have significant implications for the development of strategies aimed at blocking CRP up-regulation in bypass grafts.
Gulkarov
Iosif
I
Seymour Cohn Cardiovascular Research Laboratory, Department of Cardiothoracic Surgery, New York, New York, USA.
Pintucci
Giuseppe
G
Bohmann
Katja
K
Saunders
Paul C
PC
Sullivan
Raymond F
RF
Ferrari
Giovanni
G
Mignatti
Paolo
P
Galloway
Aubrey C
AC
D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology; D002097:C-Reactive Protein / Q000096:biosynthesis* / Q000502:physiology; D001026:Coronary Artery Bypass; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D006085:Graft Survival; D007601:Jugular Veins / Q000637:transplantation*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D002097:C-Reactive Protein