Neointimal smooth muscle cell phenotype is important in its susceptibility to cytomegalovirus (CMV) infection: a study in rat.

Abstract:

OBJECTIVE:Recently, we have found that rat CMV (RCMV) infected smooth muscle cells (SMCs) in rat carotid arteries when administered 14 days after balloon injury. In the present study we investigated (1) the long term effects of CMV infection on neointimal cross-sectional area, and (2) whether the phenotype of the intimal SMCs influences their susceptibility to active CMV infection. METHODS:In the first part of the study, rats received RCMV intravenously, two weeks after balloon catheterisation of the left carotid artery and were sacrificed twenty weeks after catheterisation. Continuous BrdU infusion was performed by subcutaneously implanted osmotic pumps during the last two weeks of life. In the second part RCMV was administered eight weeks after catheterisation and rats were sacrificed two weeks later. Immunohistochemistry was used to detect viral antigens, to determine BrdU incorporation as well as the contents of alpha-actin, desmin and vimentin in the carotid arteries. Intima and media cross-sectional areas were determined using computerized morphometry. RESULTS AND CONCLUSIONS:RCMV infection did not induce any differences in intima or media cross-sectional areas of the injured carotid artery, nor in the extent of SMC proliferation as shown by BrdU incorporation, 20 weeks after balloon catheterisation. Eight weeks after balloon catheterisation, RCMV no longer infected neointimal SMCs. This non-responsiveness to RCMV was associated with "re-differentiation" of the eight weeks old neointima, compared with two weeks after catheterization, as shown by the contents of alpha-actin, desmin and vimentin. Our data suggest that intimal SMC phenotype determines its susceptibility to active RCMV infection in vivo. Since de-differentiation of neointimal SMCs is associated with enhanced proliferation of these cells it is stated that de-differentiation or proliferation is prerequisite for infection.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Persoons MC,Daemen MJ,van Kleef EM,Grauls GE,Wijers E,Bruggeman CA

doi

10.1016/s0008-6363(97)00189-2

subject

Has Abstract

pub_date

1997-11-01 00:00:00

pages

282-8

issue

2

eissn

0008-6363

issn

1755-3245

pii

S0008636397001892

journal_volume

36

pub_type

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