Enhancement of transplantation-associated atherosclerosis by CMV, which can be prevented by antiviral therapy in the form of HPMPC.
Effects of acute cytomegalovirus (CMV) infections on transplantation-associated atherosclerosis (TxAA) were studied in a rat model for chronic vascular rejection. Rats underwent orthotopic abdominal allogeneic aorta transplantation. Neo-intima formation and media thinning was quantitated by measurement of cross-sectional surface areas (CSA) at day 50 post transplantation (Tx). Acute rat cytomegalovirus (RCMV) infection, established at the moment of maximum intimal proliferation and influx of inflammatory cells in the adventitia, resulted in enhanced neo-intima formation, accompanied by increased influx and proliferation of smooth muscle cells (smc) in the intima. This effect was completely inhibited by HPMPC, a very potent and selective inhibitor of CMV replication, indicating the virus specificity of the measured effects. Despite increased neointima formation, media thinning ("necrosis") was not affected by RCMV infection.
Bruning
J H
JH
Department of Medical Microbiology, University of Limburg, Maastricht, The Netherlands.
Persoons
M
M
Lemström
K
K
Stals
F S
FS
De Clercq
E
E
Bruggeman
C A
CA
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001011:Aorta / Q000473:pathology / Q000637:transplantation*; D001161:Arteriosclerosis / Q000517:prevention & control*; D000077404:Cidofovir; D003587:Cytomegalovirus / Q000187:drug effects / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000188:drug therapy*; D003596:Cytosine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D006084:Graft Rejection / Q000473:pathology; D008297:Male; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000517:prevention & control* / Q000821:virology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous / Q000473:pathology*; D014185:Transplantation, Isogeneic / Q000473:pathology; D017539:Tunica Intima / Q000473:pathology / Q000637:transplantation; D017540:Tunica Media / Q000473:pathology / Q000637:transplantation; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir