Common hepatic lipase gene promoter variant predicts the degree of neointima formation after carotid endarterectomy: impact of plaque composition and lipoprotein phenotype.
BACKGROUND
The common -514 C-T promoter polymorphism of the hepatic lipase gene (LIPC) and the cholesteryl ester transfer protein (CETP) gene TaqIB polymorphism affect atherogenesis. We investigated the potential relationship between these polymorphisms and the maximum-intima-media thickness (M-IMT) after carotid endarterectomy.


METHODS
The LIPC and CETP genotypes were determined by PCR in 68 patients undergoing endarterectomy. Plaque specimens were analysed for cell composition by immunocytochemistry. Six month after surgery the M-IMT of the revascularized vessel was assessed by B-mode ultrasonography.


RESULTS
The CC carriers had denser LDL particles (p<0.0005), an abundance of macrophages (p<0.0005), fewer SMCs in the carotid plaque (p<0.0005), and higher prevalence of cerebrovascular events (72% versus 28%, p=0.002) compared to CT/TT carriers. After endarterectomy, CC carriers showed a lower M-IMT than the CT/TT group (1.36 mm versus 1.76 mm, p=0.04). No association between the CETP polymorphism and either carotid plaque cellular composition or M-IMT was observed. In a multivariate analysis, M-IMT was associated with plaque cell composition (macrophages, r=-0.39; SMC, r=0.44; p<0.005 for both) but not with pre-operative LDL-C, HDL-C, triglycerides, or LDL density.


CONCLUSIONS
The LIPC promoter -514 C-T polymorphism is associated with a significantly reduced development of neointima after surgery. This effect seems to be mediated by scarcity of SMC in the plaque of CC carriers who display an excess prevalence of cerebrovascular events prior endarterectomy but are at low risk for restenosis. The pre-operative lipid phenotype plays a marginal role in the neointima formation.
Zambon
Alberto
A
Department of Medical and Surgical Sciences, University of Padua, Italy.
Puato
Massimo
M
Faggin
Elisabetta
E
Bertocco
Sandra
S
Vitturi
Nicola
N
Polentarutti
Valentina
V
Deriu
Giovanni Paolo
GP
Grego
Franco
F
Bertipaglia
Barbara
B
Rattazzi
Marcello
M
Vianello
Daniela
D
Deeb
Samir S
SS
Pauletto
Paolo
P
D016893:Carotid Stenosis / Q000097:blood* / Q000000981:diagnostic imaging / Q000601:surgery; D004247:DNA / Q000235:genetics*; D016894:Endarterectomy, Carotid / Q000009:adverse effects*; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008049:Lipase / Q000235:genetics*; D008074:Lipoproteins / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011183:Postoperative Complications; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D014461:Ultracentrifugation; D014463:Ultrasonography
C504173:LIPC protein, human; D008074:Lipoproteins; D004247:DNA; D008049:Lipase