Published Online
on July 12, 2007

A more recent version of this article appeared on August 1, 2007

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Submitted on October 17, 2006
Revised on December 8, 2006
Accepted on February 16, 2007

Early Rise in Serum VEGF and PDGF Levels Predisposes Patients With a Normal MBL2 Genotype to Restenosis After Eversion Endarterectomy

Attila Szabó MD; Judit Laki MD; Hans O. Madsen PhD; Edit Dósa MD; Zoltán Prohászka MD; Szabolcs Rugonfalvi-Kiss MD; Márta Kókai MD; György Acsádi MD; István Karádi MD; László Entz MD; László Selmeci MD; László Romics MD; George Füst MD; Peter Garred MD^*; and László Cervenak PhD

From the Department of Vascular and Cardiac Surgery (A.S., E.D., L.E., L.S.) and the Third Department of Internal Medicine (J.L., Z.P., S.R.-K., M.K., G.A., I.K., L.R., G.F.), Semmelweis University, Budapest, Hungary; the Tissue Typing Laboratory 7631 (H.O.M., P.G.), Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark; and the Research Group of Metabolism and Atherosclerosis (Z.P., I.K., L.R., G.F., L.C.), Semmelweis University and Hungarian Academy of Sciences, Budapest, Hungary.

^* To whom correspondence should be addressed. E-mail: garred{at}post5.tele.dk.

Background and Purpose--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.

Key words: atherosclerosis • endarterectomy • growth factors • mannose-binding lectin • restenosis

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