Early rise in serum VEGF and PDGF levels predisposes patients with a normal MBL2 genotype to restenosis after eversion endarterectomy.
OBJECTIVE
Recently we found that the incidence of restenosis after carotid endarterectomy was significantly higher in patients homozygous for the normal genotype of mannose-binding lectin (MBL2) than in with patients with MBL2 variant genotypes. Several growth factors are also known to contribute to restenosis. Therefore, we investigated whether early postoperative changes in serum vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) concentrations and MBL2 genotypes interact in the development of restenosis.


METHODS
Eighty-two patients who underwent carotid eversion endarterectomy and were followed up by carotid duplex scan sonography for 14 months were studied. Growth factors were measured preoperatively and 4 days after surgery.


RESULTS
Pronounced significant increases in both VEGF and PDGF predicted restenosis but only in patients who were homozygous for the normal MBL2 genotype. In this group, the adjusted odds ratios of restenosis at 14 months in patients with high versus low early VEGF and PDGF increases were 27.73 (2.42 to 317.26) and 9.23 (1.45 to 58.70), respectively.


CONCLUSIONS
These findings indicate that the development of restenosis depends on both complement activation regulated by the MBL2 gene and pathologic processes leading to enhanced production of VEGF and PDGF during the very early postoperative period.
Szabó
Attila
A
Department of Vascular and Cardiac Surgery, Semmelweis University, Budapest, Hungary.
Laki
Judit
J
Madsen
Hans O
HO
Dósa
Edit
E
Prohászka
Zoltán
Z
Rugonfalvi-Kiss
Szabolcs
S
Kókai
Márta
M
Acsádi
György
G
Karádi
István
I
Entz
László
L
Selmeci
László
L
Romics
László
L
Füst
George
G
Garred
Peter
P
Cervenak
László
L
D000368:Aged; D002339:Carotid Arteries / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D016893:Carotid Stenosis / Q000097:blood* / Q000235:genetics* / Q000601:surgery; D003165:Complement System Proteins / Q000378:metabolism; D004252:DNA Mutational Analysis; D016894:Endarterectomy, Carotid / Q000706:statistics & numerical data; D004815:Epidermal Growth Factor / Q000097:blood; D005260:Female; D005819:Genetic Markers / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006083:Graft Occlusion, Vascular / Q000097:blood / Q000235:genetics; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011446:Prospective Studies; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D005819:Genetic Markers; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D004815:Epidermal Growth Factor; D003165:Complement System Proteins