Increased arterial expression of a glycosylated haptoglobin isoform after balloon dilation.
OBJECTIVE
Haptoglobin is a novel cell migration factor that is expressed in arteries after sustained flow changes and involved in arterial restructuring. Arterial restructuring is the major determinant of arterial shrinkage after balloon dilation. Although the function of extrahepatic haptoglobin expression is not yet understood, local haptoglobin expression may provide the tissue with functionally different haptoglobin due to post-translational modifications. We hypothesized that haptoglobin expression is increased during arterial restructuring after balloon dilation and compared glycosylation patterns between arterial and liver haptoglobin.


METHODS
Arterial haptoglobin expression was studied in rabbits at 0, 2, 7, 14 and 28 days after balloon dilation (n=36) using real-time polymerase chain reaction, Western blotting and in situ hybridization. Two-dimensional gel electrophoresis and lectin affinity blotting were used to identify liver and arterial haptoglobin glycoforms.


RESULTS
Arterial haptoglobin mRNA (5.7-fold, P=0.01) and protein levels (1.4-fold, P=0.01) were increased after balloon dilation whereas liver haptoglobin expression remained constant. Haptoglobin was expressed in the adventitia of balloon dilated rabbit arteries, which was confirmed in human atherosclerotic arteries. Comparison between liver and arterial haptoglobin demonstrated the expression of artery-specific haptoglobin glycoforms.


CONCLUSIONS
This study demonstrates that arterial haptoglobin expression is increased early after balloon dilation whereas liver haptoglobin expression does not change. Furthermore, arterial haptoglobin consists of an unique set of glycoforms compared to haptoglobin produced in the liver.
Smeets
Mirjam B
MB
Experimental Cardiology Laboratory, University Medical Center, Utrecht, The Netherlands.
Sluijter
Joost P G
JP
Donners
Marjo M P C
MM
Velema
Evelyn
E
Heeneman
Sylvia
S
Pasterkamp
Gerard
G
de Kleijn
Dominique P V
DP
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002404:Catheterization / Q000009:adverse effects*; D023903:Coronary Restenosis / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D006031:Glycosylation; D006242:Haptoglobins / Q000032:analysis*; D017403:In Situ Hybridization / Q000379:methods; D008099:Liver / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D020033:Protein Isoforms / Q000032:analysis*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D006242:Haptoglobins; D020033:Protein Isoforms