HCMV-infection in a human arterial organ culture model: effects on cell proliferation and neointimal hyperplasia.
BACKGROUND
The impact of infections with the human cytomegalovirus (HCMV) for the development of atherosclerosis and restenosis is still unclear. Both a clear correlation and no correlation at all have been reported in clinical, mostly serological studies. In our study we employed a human non-injury ex vivo organ culture model to investigate the effect of an in vitro permissive HCMV-infection on cell proliferation and neointimal hyperplasia for a period of 56 days.


RESULTS
During routine-nephrectomies parts of renal arteries from 71 patients were obtained and prepared as human organ cultures. Cell free HCMV infection was performed with the fibroblast adapted HCMV strain AD169, the endotheliotropic strain TB40E, and a clinical isolate (AN 365). After 3, 7, 14, 21, 28, 35, and 56 days in culture staining of HCMV-antigens was carried out and reactive cell proliferation and neointimal thickening were analysed. Successful HCMV-infection was accomplished with all three virus strains studied. During the first 21 days in organ culture no cell proliferation or neointimal hyperplasia was detected. At day 35 and day 56 moderate cell proliferation and neointimal hyperplasia was found both in HCMV-infected segments and mock infected controls. Neointimal hyperplasia in productively HCMV-infected segments was lower than in non infected at day 35 and day 56, but relatively higher after infection with the endotheliotropic TB40E in comparison with the two other strains.


CONCLUSIONS
The data do not support the hypothesis that HCMV-infection triggers restenosis via a stimulatory effect on cell proliferation and neointimal hyperplasia in comparison to non infected controls. Interestingly however, even after lytic infection, a virus strain specific difference was observed.
Department of Internal Medicine II-Cardiology, University of Ulm, Ulm, Germany. rainer.voisard@uni-ulm.de
Rainer
R
Voisard
Tanja
T
Krügers
Barbara
B
Reinhardt
Bianca
B
Vaida
Regine
R
Baur
Tina
T
Herter
Anke
A
Lüske
Dorothea
D
Weckermann
Karl
K
Weingärtner
Wolfgang
W
Rössler
Vinzenz
V
Hombach
Thomas
T
Mertens
D000199:Actins / Q000378:metabolism; D000956:Antigens, Viral / Q000378:metabolism; D049109:Cell Proliferation; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000378:metabolism / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000821:virology; D009924:Organ Culture Techniques / Q000379:methods; D012077:Renal Artery / Q000378:metabolism / Q000473:pathology / Q000821:virology; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D014841:von Willebrand Factor / Q000378:metabolism
D000199:Actins; D000956:Antigens, Viral; D014841:von Willebrand Factor