title: P-selectin mediates the microvascular dysfunction associated with persistent cytomegalovirus infection in normocholesterolemic and hypercholesterolemic mice.
abstract: OBJECTIVE
  Cytomegalovirus has been implicated in cardiovascular disease, possibly through the induction of inflammatory processes. P-selectin and L-selectin are adhesion molecules that mediate early microvascular responses to inflammatory stimuli. This study examined the role of these selectins in the microvascular dysfunction that occurs during persistent CMV infection.
  
  
  METHODS
  C57Bl/6, P- or L-selectin-deficient mice were mock-inoculated or infected with murine CMV, and five weeks later placed on normal diet or high cholesterol diet for six weeks. P-selectin expression was measured or intravital microscopy was performed to determine arteriolar vasodilation and venular blood cell recruitment.
  
  
  RESULTS
  P-selectin expression was significantly increased in the heart, lung, and spleen of mCMV-ND, but not mCMV-HC C57Bl/6. mCMV-ND and mCMV-HC exhibited impaired arteriolar function, which was reversed by treatment with an anti-P-selectin antibody, but not L-selectin deficiency. mCMV-HC also showed elevated leukocyte and platelet recruitment. P-selectin inhibition abrogated, whereas L-selectin deficiency partially reduced these responses.
  
  
  CONCLUSIONS
  We provide the first evidence for P-selectin upregulation by persistent mCMV infection and implicate this adhesion molecule in the associated arteriolar dysfunction. P-selectin, and to a lesser extent L-selectin, mediates the leukocyte and platelet recruitment induced by CMV infection combined with hypercholesterolemia.
authors: Department of Molecular and Cellular Physiology Center for Molecular and Tumor Virology Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
authors: Evgeny
authors: E
authors: Senchenkov
authors: Mikhail V
authors: MV
authors: Khoretonenko
authors: Igor L
authors: IL
authors: Leskov
authors: Dmitry V
authors: DV
authors: Ostanin
authors: Karen Y
authors: KY
authors: Stokes
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001160:Arterioles / Q000378:metabolism / Q000821:virology; D001792:Blood Platelets / Q000378:metabolism; D006566:Herpesviridae Infections / Q000235:genetics / Q000378:metabolism*; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D019041:L-Selectin / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D019007:P-Selectin / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000906:Antibodies; D019007:P-Selectin; D019041:L-Selectin