Atherosclerosis 185 (2006) 121–126
Common hepatic lipase gene promoter variant predicts the degree of
neointima formation after carotid endarterectomy: Impact of plaque
composition and lipoprotein phenotype
Alberto Zambon
b
, Massimo Puato
a
, Elisabetta Faggin
a
, Sandra Bertocco
b
, Nicola Vitturi
b
,
Valentina Polentarutti
b
, Giovanni Paolo Deriu
c
, Franco Grego
c
, Barbara Bertipaglia
a
,
Marcello Rattazzi
a
, Daniela Vianello
b
, Samir S. Deeb
d
, Paolo Pauletto
a,∗
a
Department of Clinical and Experimental Medicine, University of Padua, Italy
b
Department of Medical and Surgical Sciences, University of Padua, Italy
c
Vascular Surgery I, University of Padua, Italy
d
Department of Medical Genetics, University of Washington, Seattle, WA, USA
Received 30 December 2004; received in revised form 6 May 2005; accepted 16 May 2005
Available online 7 July 2005
Abstract
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 polymor-
phism 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.
© 2005 Elsevier Ireland Ltd. All rights reserved.
Keywords: Hepatic lipase gene polymorphism; Cholesteryl ester transfer protein gene polymorphism; Low-density lipoprotein; Intima-media thickness; Carotid
artery; Cerebrovascular events
1. Introduction
Successful revascularization procedures are hampered by
the elevated occurrence of restenosis. Risk factors for pri-
mary atherosclerosis appear to play only a marginal role in
∗
Corresponding author. Tel.: +39 0422 328144; fax: +39 0422 322314.
E-mail address: ppauletto@ulss.tv.it (P. Pauletto).
accounting for by the restenotic process [1]. Among factors
potentially involved in restenosis, importance has been placed
on local, wall-related, factors such as cellular and molecular
characteristics of the primary atheroma [2]. The expression of
nonmuscle (NM) myosin in activated SMCs has been shown
to be of importance in human restenosis [3–5]. In patients
enrolled in the carotid atherosclerosis and restenosis study
(CARS) who underwent carotid endarterectomy, the pres-
0021-9150/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.atherosclerosis.2005.05.023