title: Cytomegalovirus infection leads to microvascular dysfunction and exacerbates hypercholesterolemia-induced responses.
abstract: Cytomegalovirus (CMV) persistently infects more than 60% of the worldwide population. In immunocompetent hosts, it has been implicated in several diseases, including cardiovascular disease, possibly through the induction of inflammatory pathways. Cardiovascular risk factors promote an inflammatory phenotype in the microvasculature long before clinical disease is evident. This study determined whether CMV also impairs microvascular homeostasis and synergizes with hypercholesterolemia to exaggerate these responses. Intravital microscopy was used to assess endothelium-dependent and -independent arteriolar vasodilation and venular leukocyte and platelet adhesion in mice after injection with either mock inoculum or murine CMV (mCMV). Mice were fed a normal (ND) or high-cholesterol (HC) diet beginning at 5 weeks postinfection (p.i.), or a HC diet for the final 4 weeks of infection. mCMV-ND mice exhibited impaired endothelium-dependent vasodilation versus mock-ND at 9 and 12 weeks and endothelium-independent arteriolar dysfunction by 24 weeks. Transient mild leukocyte adhesion occurred in mCMV-ND venules at 7 and 21 weeks p.i. HC alone caused temporary arteriolar dysfunction and venular leukocyte and platelet recruitment, which were exaggerated and prolonged by mCMV infection. The time of introduction of HC after mCMV infection determined whether mCMV+HC led to worse venular inflammation than either factor alone. These findings reveal a proinflammatory influence of persistent mCMV on the microvasculature, and suggest that mCMV infection enhances microvasculature susceptibility to both inflammatory and thrombogenic responses caused by hypercholesterolemia.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Khoretonenko
authors.forename: Igor L
authors.initials: IL
authors.lastname: Leskov
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Jennings
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Yurochko
authors.forename: Karen Y
authors.initials: KY
authors.lastname: Stokes
mesh_terms: D000818:Animals; D001160:Arterioles / Q000276:immunology / Q000473:pathology*; D002448:Cell Adhesion; D002784:Cholesterol / Q000008:administration & dosage / Q000097:blood; D003587:Cytomegalovirus / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology*; D006937:Hypercholesterolemia / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D010973:Platelet Adhesiveness / Q000276:immunology; D016133:Polymerase Chain Reaction; D014664:Vasodilation; D014699:Venules / Q000276:immunology / Q000473:pathology*
chemical_list: D004279:DNA, Viral; D002784:Cholesterol
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