The role of angiogenic and wound repair factors during CMV-accelerated transplant vascular sclerosis in rat cardiac transplants

Daniel Streblow, C. N. Kreklywich, T. Andoh, Ashlee Moses, J. Dumortier, P. P. Smith, Victor De Filippis, Klaus Frueh, Jay Nelson, Susan Orloff

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Human cytomegalovirus (HCMV) accelerates transplant vascular sclerosis (TVS), a consequence of angiogenesis (AG) and wound repair (WR). While HCMV can be localized to TVS lesions, the low number of infected cells suggests a global effect on target tissues. We used microarray analysis followed by real-time-polymerase chain reaction (RT-PCR) in an RCMV-accelerated TVS rat cardiac transplant model to determine whether CMV activates host WR and AG factors. Dysregulated cellular genes in allografts from RCMV-infected recipients were compared to those from uninfected recipients and native hearts. We demonstrated that RCMV upregulates the genes involved in WR and AG, which was highest during the critical time of TVS acceleration (21-28 days). Using a standard in vitro AG assay, virus and serum-free supernatants collected at 48 h postinfection significantly induced endothelial cell (EC) migration, branching and tubule formation compared to supernatants from mock-infected cells. Supernatants from ultraviolet (UV)-inactivated RCMV-infected cells failed to induce AG, indicating that virus replication is required. Upregulation of WR and AG genes occurs during the critical period of CMV-accelerated TVS. Targeting these genes may prevent this process and improve allograft survival.

Original languageEnglish (US)
Pages (from-to)277-287
Number of pages11
JournalAmerican Journal of Transplantation
Volume8
Issue number2
DOIs
StatePublished - Feb 2008

Fingerprint

Arteriosclerosis
Transplants
Wounds and Injuries
Cytomegalovirus
Allografts
Up-Regulation
Genes
Gene Targeting
Angiogenesis Inducing Agents
Microarray Analysis
Virus Replication
Cell Movement
Real-Time Polymerase Chain Reaction
Endothelial Cells
Cell Count
Viruses
Serum

Keywords

  • Accelerated rejection
  • Allograft vasculopathy
  • Angiogenesis
  • Arrays
  • Cardiac allograft rejection
  • Cardiac allograft vasculopathy
  • Chronic allograft rejection
  • Cyclosporine A
  • Cytomegalovirus (CMV)
  • Cytomegalovirus infection
  • Transplant vascular sclerosis
  • Virus

ASJC Scopus subject areas

  • Immunology

Cite this

The role of angiogenic and wound repair factors during CMV-accelerated transplant vascular sclerosis in rat cardiac transplants. / Streblow, Daniel; Kreklywich, C. N.; Andoh, T.; Moses, Ashlee; Dumortier, J.; Smith, P. P.; De Filippis, Victor; Frueh, Klaus; Nelson, Jay; Orloff, Susan.

In: American Journal of Transplantation, Vol. 8, No. 2, 02.2008, p. 277-287.

Research output: Contribution to journalArticle

@article{3f0e93e214424c62a3074e910b093e95,
title = "The role of angiogenic and wound repair factors during CMV-accelerated transplant vascular sclerosis in rat cardiac transplants",
abstract = "Human cytomegalovirus (HCMV) accelerates transplant vascular sclerosis (TVS), a consequence of angiogenesis (AG) and wound repair (WR). While HCMV can be localized to TVS lesions, the low number of infected cells suggests a global effect on target tissues. We used microarray analysis followed by real-time-polymerase chain reaction (RT-PCR) in an RCMV-accelerated TVS rat cardiac transplant model to determine whether CMV activates host WR and AG factors. Dysregulated cellular genes in allografts from RCMV-infected recipients were compared to those from uninfected recipients and native hearts. We demonstrated that RCMV upregulates the genes involved in WR and AG, which was highest during the critical time of TVS acceleration (21-28 days). Using a standard in vitro AG assay, virus and serum-free supernatants collected at 48 h postinfection significantly induced endothelial cell (EC) migration, branching and tubule formation compared to supernatants from mock-infected cells. Supernatants from ultraviolet (UV)-inactivated RCMV-infected cells failed to induce AG, indicating that virus replication is required. Upregulation of WR and AG genes occurs during the critical period of CMV-accelerated TVS. Targeting these genes may prevent this process and improve allograft survival.",
keywords = "Accelerated rejection, Allograft vasculopathy, Angiogenesis, Arrays, Cardiac allograft rejection, Cardiac allograft vasculopathy, Chronic allograft rejection, Cyclosporine A, Cytomegalovirus (CMV), Cytomegalovirus infection, Transplant vascular sclerosis, Virus",
author = "Daniel Streblow and Kreklywich, {C. N.} and T. Andoh and Ashlee Moses and J. Dumortier and Smith, {P. P.} and {De Filippis}, Victor and Klaus Frueh and Jay Nelson and Susan Orloff",
year = "2008",
month = "2",
doi = "10.1111/j.1600-6143.2007.02062.x",
language = "English (US)",
volume = "8",
pages = "277--287",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - The role of angiogenic and wound repair factors during CMV-accelerated transplant vascular sclerosis in rat cardiac transplants

AU - Streblow, Daniel

AU - Kreklywich, C. N.

AU - Andoh, T.

AU - Moses, Ashlee

AU - Dumortier, J.

AU - Smith, P. P.

AU - De Filippis, Victor

AU - Frueh, Klaus

AU - Nelson, Jay

AU - Orloff, Susan

PY - 2008/2

Y1 - 2008/2

N2 - Human cytomegalovirus (HCMV) accelerates transplant vascular sclerosis (TVS), a consequence of angiogenesis (AG) and wound repair (WR). While HCMV can be localized to TVS lesions, the low number of infected cells suggests a global effect on target tissues. We used microarray analysis followed by real-time-polymerase chain reaction (RT-PCR) in an RCMV-accelerated TVS rat cardiac transplant model to determine whether CMV activates host WR and AG factors. Dysregulated cellular genes in allografts from RCMV-infected recipients were compared to those from uninfected recipients and native hearts. We demonstrated that RCMV upregulates the genes involved in WR and AG, which was highest during the critical time of TVS acceleration (21-28 days). Using a standard in vitro AG assay, virus and serum-free supernatants collected at 48 h postinfection significantly induced endothelial cell (EC) migration, branching and tubule formation compared to supernatants from mock-infected cells. Supernatants from ultraviolet (UV)-inactivated RCMV-infected cells failed to induce AG, indicating that virus replication is required. Upregulation of WR and AG genes occurs during the critical period of CMV-accelerated TVS. Targeting these genes may prevent this process and improve allograft survival.

AB - Human cytomegalovirus (HCMV) accelerates transplant vascular sclerosis (TVS), a consequence of angiogenesis (AG) and wound repair (WR). While HCMV can be localized to TVS lesions, the low number of infected cells suggests a global effect on target tissues. We used microarray analysis followed by real-time-polymerase chain reaction (RT-PCR) in an RCMV-accelerated TVS rat cardiac transplant model to determine whether CMV activates host WR and AG factors. Dysregulated cellular genes in allografts from RCMV-infected recipients were compared to those from uninfected recipients and native hearts. We demonstrated that RCMV upregulates the genes involved in WR and AG, which was highest during the critical time of TVS acceleration (21-28 days). Using a standard in vitro AG assay, virus and serum-free supernatants collected at 48 h postinfection significantly induced endothelial cell (EC) migration, branching and tubule formation compared to supernatants from mock-infected cells. Supernatants from ultraviolet (UV)-inactivated RCMV-infected cells failed to induce AG, indicating that virus replication is required. Upregulation of WR and AG genes occurs during the critical period of CMV-accelerated TVS. Targeting these genes may prevent this process and improve allograft survival.

KW - Accelerated rejection

KW - Allograft vasculopathy

KW - Angiogenesis

KW - Arrays

KW - Cardiac allograft rejection

KW - Cardiac allograft vasculopathy

KW - Chronic allograft rejection

KW - Cyclosporine A

KW - Cytomegalovirus (CMV)

KW - Cytomegalovirus infection

KW - Transplant vascular sclerosis

KW - Virus

UR - http://www.scopus.com/inward/record.url?scp=38149088798&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38149088798&partnerID=8YFLogxK

U2 - 10.1111/j.1600-6143.2007.02062.x

DO - 10.1111/j.1600-6143.2007.02062.x

M3 - Article

VL - 8

SP - 277

EP - 287

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

IS - 2

ER -