The 2002 Grantees Meeting for the HIV RFA Programs

Etiology of Cardiovascular Complications of HIV Infection
Endothelial Dysfunction in HIV Infection
Cardiovascular Complications from Cocaine Abuse in HIV Infection
Genesis of Cardiomyopathy with HIV Infection and Alcohol Abuse

May 2-3, 2002

Sponsored by National Heart, Lung, and Blood Institute
National Institute on Drug Abuse
National Institutes of Health



Meeting Summary

Agenda

Roster



Meeting Summary

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This meeting was planned, organized and conducted by Lan-Hsiang Wang, Ph.D., of the National Heart, Lung, and Blood Institute and Jag H. Khalsa, Ph.D., of the Center on AIDS and Other Medical Consequences of Drug Abuse (CAMCODA), within the National Institute on Drug Abuse, NIH. A group of nationally and internationally recognized clinicians and scientists, supported by the NHLBI and NIDA, presented and discussed:


  • Current data on the etiology and underlying pathophysiology of cardiovascular complications of HIV/AIDS, substance abuse (cocaine, alcohol), and HIV infection

  • In vitro tests and in vivo models for the study of cardiovascular complications (e.g., cardiomyopathy) of HIV and substance abuse

  • Endothelial function in HIV infection

  • The problems of design and conducting such studies in clinical populations

Finally, the attendees made recommendations for future research. The recommendations included the study of:

  • The role of covariates in HIV-related cardiovascular complications

  • Role of other pathogens in HIV-related cardiovascular complications

  • Autoimmune mechanisms in HIV-related cardiac conditions, particularly in combination with other pathogens

  • Genetic predisposition for transition to dilated cardiomyopathy

  • Incidence, prevalence, and pathophysiology of HIV-related cardiovascular disease in other vulnerable populations such as women, infants, and older individuals exposed to HIV and substance abuse

  • Influence of other conditions such as diabetes, atherosclerosis, as well as lifestyle and behavior choices such as smoking and recreational drug abuse on HIV-related cardiovascular complications

  • Mechanisms of cellular injury in HIV-related cardiovascular complications

  • Interactions of viral replication, immune system activation, inflammatory pathways, and reactive oxygen species in HIV-related cardiovascular complications

  • Metabolic/energetic mechanisms such as the role of mitochondrial ATP production, cardiac myocyte energetics, increased reactive oxygen species, altered oxygen utilization, and changes in gene expression in HIV-related cardiovascular complications

  • Role of highly active antiretroviral therapies (HAART) in HIV-related cardiovascular complications

  • Pharmacokinetic drug interactions between HAART and pharmaceuticals use in the treatment of cardiac disease

  • Interactions between immune cell (infected and/or uninfected) and cardiac myocytes and their effects on recruitment mechanisms, gene expression alterations, and cell-cell signaling events

  • Role of hypothalamic-pituitary-adrenal axis in HIV progression and HIV-related cardiovascular complications

  • Pre-clinical investigations for therapies for HIV/AIDS-related cardiovascular complications

  • Animal models for studying the effects of antiretroviral and immunorestorative therapies on HIV-related cardiovascular complications

  • Animal models for testing optimal therapies for the treatment of HIV-related cardiovascular complications

  • Therapeutics and prevention trials for HIV/AIDS-related cardiovascular complications

  • Optimal therapies for treating HIV-related cardiomyopathy considering whether these therapies should be different from other forms of cardiomyopathy

  • Possibility and advantage of early intervention for HIV-related cardiovascular complications

  • Alternative therapies (e.g., anti-oxidants, immunomodulators, nutritional therapies) for HIV-related cardiovascular complications

 

Agenda

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Thursday, May 2, 2002

8:00 a.m.

Registration

8:30 a.m.

Welcome and Introduction
Lan-Hsiang Wang, NHLBI
Jag H. Khalsa, NIDA
Hannah H. Peavy, NHLBI
Sandra Colombini Hatch, NHLBI

8:44 a.m.

Lance Terada (1)
University of Texas Southwestern
Effect of HIV Tat on Endothelial Cell Function

9:00 a.m.

Mitchell Finkel (16)
West Virginia University
P38 MAP Kinase Regulates Negative Inotropic Effect of HIV gp120 on Cardiac Myocytes through Troponin I Phosphorylation

9:20 a.m.

Jian-Feng Wang (3)
Beth Israel Deaconess Medical Center
Functional Studies of HIV-Tat Effects on Endothelium

9:40 a.m.

Winnie Henderson (4)
Oregon Health Sciences University
HIV-1 vpu and tat Modulate Endothelial Cell-B Lymphoma Cell Interactions: Implications for AIDS-Associated Non-Hodgkin's Lymphoma

10:00 a.m.

Break

10:20 a.m.

John Ho (5)
Cornell University
HIV-1 Activates Innate Immune Cells via Toll-Like Receptor 2

10:40 a.m.

Emily D. Overholser (6)
Johns Hopkins University
Mechanisms of Endothelial Cell Dysfunction in SIV Infection

11:00 a.m.

Lingjun Zhao (7)
Saint Louis University Medical Center
Regulation of Myosin Light Chain Phosphorylation by HIV-1 Vpr

11:20 a.m.

Changyi Chen (8)
Baylor College of Medicine
HIV-1 gp120 Down-Regulates Endothelial Nitric Oxide Synthase (eNOS) Expression in Human Endothelial Cells

11:40 a.m.

Kwang Sik Kim (9)
Johns Hopkins University
Gp120 Induces Cytotoxicity of Human Brain Microvascular Endothelial Cells

12:00 noon

Lunch

1:00 p.m.

Poster Session (Atrium)
Posters will be displayed from 8:30 a.m. until 5 p.m. Poster presenters with odd numbers will be present from 1 p.m. to 1:50 p.m. Poster presenters with even numbers will be present from 1:50 p.m. to 2:40 p.m.

Harris McFerrin (2)--poster presentation only
Tulane University
Molecular Mechanism of Tat-Induced Angiogenesis

2:40 p.m.

Break

3:00 p.m.

Douglas Larson (10)
University of Arizona
Dilated Cardiomyopathy in Murine Acquired Immunodeficiency Syndrome
(MAIDS)

3:20 p.m.

Ronald Watson (11)
University of Arizona
Selenium Supplementation Decreases Coxsackievirus Heart Disease During
Murine AIDS

3:40 p.m.

J. Bruce Sundstrom (12)
Emory University
An in vitro Model for Investigating the Role of Mast Cells in Mechanisms of Increased Fibrosis Associated with AIDS-Related Cardiomyopathies

4:00 p.m.

Debasis Mondal (13)
Tulane University
Synergistic Effects of Cocaine and the Inflammatory Cytokines in
Modulating Vascular Endothelial Cell Function

4:20 p.m.

Guha Krishnaswamy (14)
East Tennessee State University
Role of the Inflammatory Network in Cocaine and HIV-Mediated
Atherogenesis

4:40 p.m.

Shenghan Lai (17)
Johns Hopkins University
Association of Cocaine Use With Coronary Calcification in Injecting Drug
Users in Baltimore

5:00 p.m.

Recommendations for Future Directions
Ronald Watson

5:20 p.m.

Conclusion of Today's Program

Friday, May 3, 2000

8:30 a.m.

Milan Fiala (15)
University of California Los Angeles
(A) Human Immunodeficiency Virus Type 1 Enters Brain and Coronary Endothelia by Macropinocytosis Dependent upon Lipid Rafts.
(B) Cocaine Binds to a G-Protein Coupled Receptor, Signals and Restructures Coronary Artery Endothelial Cells.

8:50 a.m.

John Bauer (18)
Ohio State University
Cocaine Induced Cardiotoxicity in Mice

9:10 a.m.

Roy Sutliff (19)
Emory University
Cocaine Administration Increases LV Mass in HIV-1 Transgenic Mice

9:30 a.m.

Sonia Flores (20)
University of Colorado
Evidence of Inflammation in Tat-Transgenic Mice

9:50 a.m.

John Bauer (21)
Ohio State University
Mechanistic Studies of Retrovirus Related Cardiac Dysfunction: the Murine AIDS Model and Human HIV Infection

10:10 a.m.

Douglas Wallace (22)
Emory University
Ethanol and AIDS Cardiomyopathy: A Mitochondrial Connection?

10:30 a.m.

Break

10:50 a.m.

Paul Jolicoeur (23)
Clinical Research Institute of Montreal
Studies of Cardiac Disease in HIV-1 Transgenic Mice

11:10 a.m. .

William Lewis (24)
Emory University
Combined Antiretroviral Therapy Causes Cardiomyopathy and Elevates
Plasma Lactate in Transgenic AIDS Mice

11:30 a.m.

Richard Shannon (25)
New England Regional Primate Research Center
Cellular Pathways Involved in Myocardial Injury in Simian AIDS: Role of
Cytokines, Inducible Nitric Oxide, and CD95

11:50 a.m.

Milan Fiala (26)
University of California Los Angeles
HIV-1 Envelope Protein gp120 Induces Cardiomyocyte Apoptosis and Is Associated with HIV-1 Cardiomyopathy

12:10 p.m.

Neil Bowles (27)
Baylor College of Medicine
The Pathogenesis of Heart Disease in HIV-Infected Children

12:30 p.m.

Closing Remarks

12:40 p.m.

Adjournment of Meeting



Roster

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Aftab A. Ansari, Ph.D.
Departments of Pathology
and Laboratory Medicine
Winship Cancer Center, Room B4107
Emory University School of Medicine
1365B Clifton Road
Atlanta, GA 30322
pathaaa@emory.edu

Sheila A. Barber, Ph.D.
Assistant Professor
Division of Comparative Medicine
Johns Hopkins University School of Medicine
Jefferson Street Building, Room 3-127
600 North Wolfe Street
Baltimore, MD 21287
sabarber@jhmi.edu

John A. Bauer, Ph.D.
Center for Developmental
Pharmacology and Toxicology
Children's Research Institute
700 Children's Drive
Columbus, OH 43205
BauerJ@pediatrics.ohio-state.edu

Neil E. Bowles, Ph.D.
Assistant Professor
Section of Cardiology
Department of Pediatrics
Baylor College of Medicine
Room 333E
1 Baylor Plaza
Houston, TX 77030
nbowles@bcm.tmc.edu

Changyi J. Chen, M.D., Ph.D.
Professor of Surgery
Michael E. DeBakey Department of Surgery
Baylor College of Medicine
6550 Fannin, SM 1661
Houston, TX 77030
jchen@bcm.tmc.edu

Adela Cota-Gomez, Ph.D.
Webb-Waring Institute
Health Sciences Center
Box C321
4200 East Ninth Avenue
Denver, CO 80262
adela.cota-gomez@uchsc.edu

Milan Fiala, M.D.
Cardiovascular Research Lab
UCLA, 3645 MRL
675 Charles Young Drive South
Los Angeles, CA 90095-1760
fiala@ucla.edu

Mitchell S. Finkel, M.D. FACP, FACC
Professor and Vice-Chairman
Department of Medicine
Professor of Physiology and Pharmacology
West Virginia University Cardiology
Medical Center Drive
Morgantown, WV 26506-9157
mfinkel@hsc.wvu.edu

Sonia Flores, Ph.D.
Webb-Waring Institute
Health Sciences Center
University of Colorado
4200 E Ninth Ave., Box C321
Denver, CO 80262
SONIA.FLORES@UCHSC.EDU

Jerome E. Groopman, M.D.
Professor of Medicine
HIM Building, Room 351
Harvard Medical School
4 Blackfan Circle
Boston, MA 02115
jgroopma@caregroup.harvard.edu

Sandra Colombini Hatch, M.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
Two Rockledge Center, Room 10124
6701 Rockledge Drive, MSC 7952
Bethesda, MD 20892-7952
hatchs@nhlbi.nih.gov

Winnie W. Henderson, M.S.
Department of Molecular Microbiology and Immunology
Basic Sciences Building, Room 6564
Oregon Health Sciences University
Mail Code L220
3181 SW Sam Jackson Park Road
Portland, OR 97201
hendersw@ohsu.edu

John L. Ho, M.D.
Weill College of Medicine
Cornell University
Visiting Scientist
Aaron Diamond AIDS Research Center
Room 711
455 First Avenue
New York, NY 10016
jlho@adarc.adarc.org

Paul Jolicoeur, M.D., Ph.D.
Laboratory of Molecular Biology
Department of Microbiology and
Immunology
Clinical Research Institute of Montreal
110 Avenue des Pins, Ouest
Montréal, Québec, Canada H2W 1R7
jolicop@ircm.qc.ca

Jag H. Khalsa, Ph.D.
Health Scientist Administrator
Center on AIDS and Other Medical Consequences of Drug Abuse
National Institute on Drug Abuse
National Institutes of Health
Neuroscience Center, Room 5198
MSC 9593
6001 Executive Boulevard
Bethesda, MD 20892-9593
jk98p@nih.gov

Kwang Sik Kim, M.D.
Pediatric Infectious Diseases
Johns Hopkins University
School of Medicine
600 North Wolfe Street, Park 256
Baltimore, MD 21287
kwangkim@jhmi.edu

Guha Krishnaswamy, M.D.
Department of Medicine
East Tennessee State University
Johnson City, TN 37614-0622
krishnas@ACCESS.ETSU.EDU

Shenghan Lai, M.D.
Epidemiology, E6141
Johns Hopkins
615 North Wolfe Street
Baltimore, MD 21205
shlai@jhsph.edu

Douglas F. Larson, Ph.D.
School of Medicine
University of Arizona
Tucson, AZ 85724
dflarson@u.arizona.edu

William Lewis, M.D.
Department of Pathology
Room 7117 WMRB
Emory University School of Medicine
1639 Pierce Drive
Atlanta, GA 30322
wlewis@emory.edu

Joao Lima, M.D.
Cardiology Division
Department of Medicine
School of Medicine
Johns Hopkins University
600 North Wolfe Street
Baltimore, MD 21287
jlima@jhmi.edu

Kai Liu, M.D.
Department of Medicine
East Tennessee State University
James H. Quillen College of Medicine
Box 70622
Johnson City, TN 37614-0622
liuk@access.etsu.edu

Harris McFerrin, M.S.
Microbiology Department
Room 5704, Box SL-38
Tulane University
1430 Tulane Avenue
New Orleans, LA 70112
Mharris1@tulane.edu

Michael J. Mihm, Ph.D.
Division of Pharmacology
College of Pharmacy
The Ohio State University
411 Riffe Building
500 West 12th Avenue
Columbus, OH 43210
mihm.2@osu.edu

Debasis Mondal, Ph.D.
Department of Pharmacology
Tulane University School of Medicine
New Orleans, LA 70112
dmondal@tulane.edu

Ashlee Moses, Ph.D.
Vaccine and Gene Therapy Institute
Oregon Health Sciences University
505 NW 185th Avenue
Beaverton, OR 97006
mosesa@ohsu.edu

Emily Overholser, B.S.
Division of Comparative Medicine
Johns Hopkins University
Jefferson Street Building, Room 3-127
600 North Wolfe Street
Baltimore, MD 21287
eoverhol@mail.jhmi.edu

Pierre Paradis, Ph.D.
Institut de Recherches Cliniques
de Montreal
110 avenue de Pins Ouest
Montreal, Quebec
Canada, H2W 1R7
Pierre_Paradis@ircm.qc.ca

Lisa Parvis, B.S.
Division of Comparative Medicine
Johns Hopkins University
Jefferson Street Building, Room 3-127
600 North Wolfe Street
Baltimore, MD 21287
lmp@hotmail.com

Hannah H. Peavy, M.D.
AIDS/TB Scientific Research Group
Lung Biology and Disease Program
Division of Lung Diseases
National Heart, Lung, and Blood Institute
Two Rockledge Centre, Suite 10018
6701 Rockledge Drive, MSC 7952
Bethesda, MD 20892-7952
PeavyH@NHLBI.NIH.GOV

Scott Raidel, M.S.
Department of Pathology
Room 7117 WMRB
Emory University School of Medicine
1639 Pierce Drive
Atlanta, GA 30322
sraidel@emory.edu

Richard P. Shannon, M.D.
Department of Medicine
Alletheny General Hospital
320 East North Avenue
Pittsburgh, PA 15212
RSHANNON@wpahs.org

J. Bruce Sundstrom, Ph.D.
Department of Pathology
and Laboratory Medicine
Emory University School of Medicine
Winship Cancer Center, Room B4337
1365B Clifton Road
Atlanta, GA 30322
jsundst@emory.edu

Roy Sutliff, Ph.D.
Department of Pathology
Room 7117 WMRB
Emory University School of Medicine
1639 Pierce Drive
Atlanta, GA 30322
rsutlif@emory.edu

Lance S. Terada, M.D.
University of Texas Southwestern, and
The Dallas Veterans Affairs Medical Center
Mail Code 151
4500 South Lancaster
Dallas, TX 75216
Lance.Terada@med.va.gov

Douglas C. Wallace, Ph.D.
Center for Molecular Medicine
Emory University School of Medicine
1462 Clifton Road, Room 420
Atlanta, GA 30322
dwallace@Gen.Emory.Edu

Jian-Feng Wang, Ph.D.
Division of Experimental Medicine
Harvard Institutes of Medicine, # 342
4 Blackfan Circle
Boston, MA 02115
jwang2@caregroup.harvard.edu

Lan-Hsiang Wang, Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
National Institutes of Health
Two Rockledge Centre, Room 9206
6701 Rockledge Drive, MSC 7940
Bethesda, MD 20892-7940
LW72F@NIH.GOV

Khaled Zerria, Ph.D.
Division of Infectious Diseases
Cornell University, Room A479
1300 York Avenue
New York, NY 10021
zerria_khaled@excite.com

Ling-Jun Zhao, Ph.D.
Institute for Molecular Virology
St. Louis University Medical Center
3681 Park Avenue
St. Louis, MO 63110
zhaol@slu.edu

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