2008
DOI: 10.1111/j.1600-6143.2007.02062.x
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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-infect… Show more

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Cited by 46 publications
(44 citation statements)
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“…We have shown that RCMV accelerates the development of TVS/CR in rat heart allografts, although widespread infection is not observed with transplanted organs (39). A comparison of transcriptomes from infected and uninfected heart allografts indicated that RCMV upregulated host genes involved in AG and WH, suggesting that RCMV may accelerate TVS formation through the induction and secretion of AG/WH factors.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…We have shown that RCMV accelerates the development of TVS/CR in rat heart allografts, although widespread infection is not observed with transplanted organs (39). A comparison of transcriptomes from infected and uninfected heart allografts indicated that RCMV upregulated host genes involved in AG and WH, suggesting that RCMV may accelerate TVS formation through the induction and secretion of AG/WH factors.…”
Section: Resultsmentioning
confidence: 99%
“…AG is an important component of WH, involving inflammation (46), tissue formation, and remodeling, whereby a local milieu created by the coordinated action of growth factors, cytokines, enzymes, extracellular matrix (ECM) components, and inflammatory cells interacts with the injured tissue, the result of which is the reestablishment of a physiological barrier (16). Recent analysis of the RCMV-induced cellular transcriptome demonstrated that a significant number of RCMV-dysregulated genes are involved in WH/AG (39). We hypothesize a mechanism of CMV-accelerated TVS/CR whereby virally induced secretion of cytokines and growth factors is involved.…”
mentioning
confidence: 99%
“…9). We performed heart transplants using the F344/Lewis rat model as previously described (25,26,(41)(42)(43) and infected allograft recipients with the r129⌬NT mutant virus (5 ϫ 10 5 PFU), and we compared the time to rejection and the severity of TVS to those of the recipients infected with RCMV-BAC (5 ϫ 10 5 PFU) and uninfected controls. The time to rejection was significantly longer in the RCMV-r129⌬NT recipients (100 Ϯ 0 days, study endpoint) than that inseen in the RCMV-BAC-infected recipients (46.25 Ϯ 2.8 days) (P Ͻ 0.0001) (Fig.…”
Section: Fig 6 Rcmv R129 Induces the Migration Of T Cells Primary Spmentioning
confidence: 99%
“…Total RNA extracted using the TRIzol method (Life Technologies) from infected fibroblasts or tissues from infected rats was analyzed by quantitative reverse transcriptase PCR (RT-PCR) for the presence of r129 gene expression using the primers CG GACCTCAGAACGGACATAC (forward) and TCTCTGCAGGATAGTTG GATCTTG (reverse) and probe AATCTGACCAGACATGTATC. cDNA was generated using Superscript III (Invitrogen Life Technologies), analyzed using an ABI StepOne real-time PCR system, and normalized to L32 (41,42). Gene amplicons served as quantification standards (sensitivity, Յ100 copies/ gene).…”
Section: Cells and Virusesmentioning
confidence: 99%
“…16,17 Cytomegalovirus is known to be associated with an increased incidence of CAV, which in turn is associated with enhancement of multiple genes associated with wound repair and angiogenesis. 18,19 Costimulatory Signals Costimulatory signals are important for stimulation of T cells and inflammatory cell recruitment into the allograft. 20 It has been reported that CAV correlates with expression of adhesion molecules, including intracellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule-1, and the E-and P-selectins.…”
Section: Pathology Of Cavmentioning
confidence: 99%