Cited by 125Cytomegalovirus and herpesvirus researchTransplantation: Methods and OutcomesViral-associated cancers and disorders

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Mechanisms of Cytomegalovirus-Accelerated Vascular Disease: Induction of Paracrine Factors That Promote Angiogenesis and Wound Healing

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Streblow, D. N., Dumortier, J., Moses, A. V., Orloff, S. L., Nelson, J. A.·2008·Current Topics in Microbiology and Immunology

DOI 10.1007/978-3-540-77349-8_22PMC PMC2699259

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Abstract

Human cytomegalovirus (HCMV) is associated with the acceleration of a number of vascular diseases such as atherosclerosis, restenosis, and transplant vascular sclerosis (TVS). All of these diseases are the result of either mechanical or immune-mediated injury followed by inflammation and subsequent smooth muscle cell (SMC) migration from the vessel media to the intima and proliferation that culminates in vessel narrowing. A number of epidemiological and animal studies have demonstrated that CMV significantly accelerates TVS and chronic rejection (CR) in solid organ allografts. In addition, treatment of human recipients and animals alike with the antiviral drug ganciclovir results in prolonged survival of the allograft, indicating that CMV replication is a requirement for acceleration of disease. However, although virus persists in the allograft throughout the course of disease, the number of directly infected cells does not account for the global effects that the virus has on the acceleration of TVS and CR. Recent investigations of up- and downregulated cellular genes in infected allografts in comparison to native heart has demonstrated that rat CMV (RCMV) upregulates genes involved in wound healing (WH) and angiogenesis (AG). Consistent with this result, we have found that supernatants from HCMV-infected cells (HCMV secretome) induce WH and AG using in vitro models. Taken together, these findings suggest that one mechanism for HCMV acceleration of TVS is mediated through induction of secreted cytokines and growth factors from virus-infected cells that promote WH and AG in the allograft, resulting in the acceleration of TVS. We review here the ability of CMV infection to alter the local environment by producing cellular factors that act in a paracrine fashion to enhance WH and AG processes associated with the development of vascular disease, which accelerates chronic allograft rejection.

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Authors: Streblow, D. N., Dumortier, J., Moses, A. V., Orloff, S. L., & Nelson, J. A.
Affiliations: Oregon Health & Science University (US)
Corresponding author: Streblow, D. N.
ORCID: Streblow, D. N.
Moses, A. V.
Orloff, S. L.
Nelson, J. A.
Venue: Current Topics in Microbiology and Immunology
Publisher: Springer Berlin Heidelberg
Published: 2008
Volume: 325
Pages: 397-415
ISSN: 0070-217X (ISSN-L)
DOI: 10.1007/978-3-540-77349-8_22
PMC: PMC2699259
OpenAlex: W125742586
Cited by: 125
References: 65
Citations by year: 2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 8 · 2015: 6 · 2014: 10 · 2013: 11 · 2012: 15
FWCI: 38.67
Type: book chapter
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Current topics in microbiology and immunology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Veterans Affairs
American Heart Association
National Institutes of Health
National Heart, Lung, and Blood Institute (HL 66238-01, R01HL083194, R01HL071695, HL 083194, R01HL065754, HL65754, R01HL085451, HL71695, R01HL066238, R01HL088603)
National Institute of Allergy and Infectious Diseases (AI21640, R37AI021640, R01AI021640)
Topics: Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
Keywords: human cytomegalovirus, vascular disease, chronic rejection, angiogenesis, wound healing, paracrine signaling, secretome, cytokines and growth factors, rat cytomegalovirus, atherosclerosis, restenosis, smooth muscle cell proliferation, ganciclovir
MeSH terms: Animals, Cytomegalovirus Infections, Cytomegalovirus, Humans, Sclerosis, Vascular Diseases, Cytokines, Intercellular Signaling Peptides and Proteins, Rats

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Mechanisms of Cytomegalovirus-Accelerated Vascular Disease: Induction of Paracrine Factors That Promote Angiogenesis and Wound Healing

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