Biology Reference
In-Depth Information
Mechanisms of Cytomegalovirus-Accelerated
Vascular Disease: Induction of Paracrine
Factors That Promote Angiogenesis
and Wound Healing
D. N. Streblow(
ΓΌ
) , J. Dumortier , A. V. Moses , S. L. Orloff , J. A. Nelson
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 398
Tissue Repair and Angiogenic Factors Mediate TVS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 398
Animal Models of CMV-Accelerated Graft Rejection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400
RCMV Accelerates TVS and CR in a Rat Heart Transplantation Model . . . . . . . . . . . . . . . 400
RCMV Induces Allograft AG and WH Genes During the Acceleration of TVS . . . . . . . . . 401
In Vitro Models of HCMV-Mediated Wound Healing and Angiogenesis . . . . . . . . . . . . . . . 402
What Factors Constitute the HCMV Secretome? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 405
HCMV Secretome Induces Angiogenesis in Endothelial Cells. . . . . . . . . . . . . . . . . . . . . . . 407
HCMV Secretome Induces Wound Healing in Endothelial Cells . . . . . . . . . . . . . . . . . . . . . 408
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 411
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 412
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 replica-
tion 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,
D.N. Streblow
Vaccine and Gene Therapy Institute and Department of Molecular Microbiology
and Immunology, Oregon Health and Science University, Portland , OR 97201 , USA
streblow@ohsu.edu
