Short communication
Hepatitis C virus RNA localization in human carotid plaques

https://doi.org/10.1016/j.jcv.2009.10.005Get rights and content

Abstract

Background

Hepatitis C virus (HCV) infection has certain characteristics that enable it to play an important role in atherosclerosis. Some studies report its association with an increased risk of carotid artery plaque.

Objectives

The aim of this study was to evaluate the presence of HCV genomic sequences and replicative intermediates in plaque tissues.

Study Design

A cohort of consecutive, prospectively recruited patients with HCV infection and chronic ischemic heart disease from the Cardiology, Vascular Surgery and Hepatology Units of a University Hospital in Florence, Italy, were studied.

Results

Positive-strand HCV RNA was detected in seven carotid plaque tissues from anti-HCV-positive patients and was not detected in the nine carotid plaque tissues obtained from anti-HCV-negative patients. In three patients, HCV RNA was found in carotid plaque and not in serum. HCV replicative intermediates were detected in three plaque samples. Direct sequencing of HCV RNA from the plaque and serum showed HCV genotypes 2 (five cases) and 1 (two cases).

Conclusions

The novel finding of HCV RNA sequences in plaque tissue strongly suggests an active local infection. This in turn makes it conceivable that the virus may exert local action in carotid atherosclerosis.

Section snippets

Background

After the first report of an association of viral infection and atherosclerosis in 1970,1 evidence is accumulating that infections are involved in the development and progression of atherosclerosis, with special focus on carotid and coronary lesions.2, 3 The pathogenetic mechanisms may vary and are still poorly understood. Localization of the infective agent inside the plaque has been shown for most pathogens for whom a deeper evidence of such an association exists, suggesting the importance of

Objective

Based on these observations, the aim of the study was to prospectively evaluate the possibility of the presence of HCV infection in carotid plaque tissue.

Study population

Plaque and serum samples were obtained from 10 consecutive anti-HCV-positive patients with chronic ischemic heart disease and hemodynamic carotid stenosis who underwent percutaneous transluminal carotid angioplasty (Table 1) and from 9 age/sex matched anti-HCV-negative (control) patients. All patients had >80% carotid stenosis grade and were identified as candidates for carotid endoarterectomy according to the routine medical practices of the vascular Surgery Department.

The main demographic,

Results

HCV RNA sequences were detected in five serum samples (pts. 2, 6, 7, 9 and 10) and seven plaque tissue samples (pts. 3, 4, 5, 6, 7, 9 and 10) from anti-HCV-positive patients (Table 1 and Fig. 1). The mean viral load (detection of positive-strand HCV RNA) in serum was 7.79 ± 4.21 × 105 IU/mL. No HCV RNA sequences were detected in anti-HCV-negative subjects (data not shown). HCV genotype analysis showed five out of seven typeable patients were infected by HCV genotype 2 (pts. 3, 4, 5, 7 and 10) and

Discussion

Available data suggest that HCV is an independent risk factor for carotid atherosclerosis, even though the mechanism involved is unknown. The present study, for the first time, demonstrates the presence of HCV genomic sequences and replicative intermediates in plaque tissues, strongly suggesting the possibility of an active infection of the carotid plaque. The detection of HCV sequences in the sole plaque tissue in three patients further supports viral localization rather than contamination by

Competing interests

None declared.

Ethical approval

Not required.

Acknowledgments

This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC), Istituto Toscano Tumori (ITT) and Ente Cassa di Risparmio di Firenze.

References (32)

  • C. Espinola-Klein et al.

    Impact of infectious burden on progression of carotid atherosclerosis

    Stroke

    (2002)
  • A. Prasad et al.

    Predisposition to atherosclerosis by infections: role of endothelial dysfunction

    Circulation

    (2002)
  • M.V. Kalayoglu et al.

    Chlamydia pneumoniae as an emerging risk factor in cardiovascular disease

    JAMA

    (2002)
  • F.C. Gibson et al.

    Porphyromonas gingivalis mediated periodontal disease and atherosclerosis: disparate diseases with commonalities in pathogenesis through TLRs

    Curr Pharm Des

    (2007)
  • M.G. Hendrix et al.

    High prevalence of latently present cytomegalovirus in arterial walls of patients suffering from grade III atherosclerosis

    Am J Pathol

    (1990)
  • G. Stoll et al.

    Inflammation and atherosclerosis: novel insights into plaque formation and destabilization

    Stroke

    (2006)
  • Cited by (122)

    View all citing articles on Scopus
    View full text