Mechanisms of cytomegalovirus-accelerated vascular disease: Induction of paracrine factors that promote angiogenesis and wound healing

Research output: Contribution to journalArticle

104 Citations (Scopus)

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 immunemediated 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.

Original languageEnglish (US)
Pages (from-to)397-415
Number of pages19
JournalCurrent Topics in Microbiology and Immunology
Volume325
DOIs
StatePublished - 2008

Fingerprint

Angiogenesis Inducing Agents
Cytomegalovirus
Vascular Diseases
Arteriosclerosis
Wound Healing
Allografts
Transplants
Viruses
Ganciclovir
Genes
Smooth Muscle Myocytes
Cell Movement
Antiviral Agents
Epidemiologic Studies
Atherosclerosis
Intercellular Signaling Peptides and Proteins
Up-Regulation
Down-Regulation
Cytokines
Inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology (medical)
  • Immunology
  • Microbiology
  • Immunology and Microbiology(all)

Cite this

@article{fba5e94f47a841a0877c4462f57eb259,
title = "Mechanisms of cytomegalovirus-accelerated vascular disease: Induction of paracrine factors that promote angiogenesis and wound healing",
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 immunemediated 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.",
author = "Daniel Streblow and J. Dumortier and Ashlee Moses and Susan Orloff and Jay Nelson",
year = "2008",
doi = "10.1007/978-3-540-77349-8_22",
language = "English (US)",
volume = "325",
pages = "397--415",
journal = "Current Topics in Microbiology and Immunology",
issn = "0070-217X",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Mechanisms of cytomegalovirus-accelerated vascular disease

T2 - Induction of paracrine factors that promote angiogenesis and wound healing

AU - Streblow, Daniel

AU - Dumortier, J.

AU - Moses, Ashlee

AU - Orloff, Susan

AU - Nelson, Jay

PY - 2008

Y1 - 2008

N2 - 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 immunemediated 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.

AB - 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 immunemediated 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.

UR - http://www.scopus.com/inward/record.url?scp=48849108250&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=48849108250&partnerID=8YFLogxK

U2 - 10.1007/978-3-540-77349-8_22

DO - 10.1007/978-3-540-77349-8_22

M3 - Article

C2 - 18637518

AN - SCOPUS:48849108250

VL - 325

SP - 397

EP - 415

JO - Current Topics in Microbiology and Immunology

JF - Current Topics in Microbiology and Immunology

SN - 0070-217X

ER -