IMMUNOMODULATION OF RETROVIRAL CARDIOPATHOLOGY

Project: Research project

Description

DESCRIPTION Pericardial effusion, cardiomyopathy, and left ventricular dysfunction are prevalent in patients with AIDS. The applicants' model of murine retrovirus infection mimics much of the immune dysfunction and cardiac toxicity found during HIV infection. They expect that cytokine dysregulation and increased oxidative stress in the mouse heart due to murine retrovirus infection will increase the formation of NfkB expression resulting in of ICAM-1 and T-helper cell hyperactivtion and secretion of cytokines. This cascade will stimulate PMN and endothelial cell activation and promote the formation of iNOS, resulting in cardiac muscle and endothelial cell damage and ventricular dysfunction. They will perform molecular analysis of NfkB translocation to the nucleus. They will measure simultaneously the resulting RNA message and proteins for iNOS or ICAM-1 in heart tissues. The left ventricular function will be quantitated in vivo with pressure volume loop to define the ventricular dysfunction and characterize the therapeutic effect of immunomodulators. They propose to examine the PMN-mediated tissue injury hypothesis in the heart and coronary vasculative. They will investigate PMN sequestration and activation in the heart and test for oxidative damage. They will correlate the retroviral progression to the coronary microvascular injury through intravital microscopy, PMN accumulation and PMN function. They will limit the deleterious cardiac effects during retrovial infection by preventing dysfunctional cytokine production, slowing the resulting immune dysregulation and increased oxidative damage. They will examine the efficacy of their proven methods that prevented much of the cytokine dysregulation and oxidative damage to the heart: T-cell receptor Vbeta 8.1 injection, vitamin E supplementation, and interferon-gamma or anti IL-4 antisera injection. They will also accentuate cytokine dysregulation by IL-4 injection to accelerate immune dysfunction and cardiopathology. These model studies will increase understanding of retrovirus induced immune dysfunction and its role in cardiac pathology. The treatments that found to prevent cytokine dysregulation and cardiotoxicitiy in retrovirally infected mice will then be applicable to reducing heart disease in HIV infected patients (End of Abstract)
StatusFinished
Effective start/end date9/30/979/29/02

Funding

  • National Institutes of Health: $236,719.00
  • National Institutes of Health: $47,344.00
  • National Institutes of Health
  • National Institutes of Health: $189,375.00
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Immunomodulation
Cytokines
Retroviridae Infections
Ventricular Dysfunction
Intercellular Adhesion Molecule-1
Interleukin-4
Injections
Endothelial Cells
Pericardial Effusion
Wounds and Injuries
Immunologic Factors
Left Ventricular Dysfunction
Therapeutic Uses
Retroviridae
Helper-Inducer T-Lymphocytes
T-Cell Antigen Receptor
Vitamin E
Cardiomyopathies
Left Ventricular Function
Cardiac Myocytes

ASJC

  • Medicine(all)