Journal article
Cytomegalovirus Infection Leads to Microvascular Dysfunction and Exacerbates Hypercholesterolemia-Induced Responses
The American journal of pathology, Vol.177(4), pp.2134-2144
01 Oct 2010
PMCID: PMC2947306
PMID: 20802174
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Cytomegalovirus Infection Leads to Microvascular Dysfunction and Exacerbates Hypercholesterolemia-Induced Responses
- Creators
- Mikhail V. Khoretonenko - Louisiana State University Health Sciences Center ShreveportIgor L. Leskov - Louisiana State University Health Sciences Center ShreveportStephen R. Jennings - Drexel UniversityAndrew D. Yurochko - Louisiana State University Health Sciences Center ShreveportKaren Y. Stokes - Louisiana State University Health Sciences Center Shreveport
- Publication Details
- The American journal of pathology, Vol.177(4), pp.2134-2144
- Publisher
- American Society for Investigative Pathology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019167649804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Pathology