HIV EC COMPLICATIONS · Role of poly (ADP-ribose) polymerase and oxidative stress in cardiovascular complications of HIV infection
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-07-01 → 2007-06-30
- EU contribution
- €80,000
- Participants
- 1
- Scheme
- IRG
Lines connect the coordinator with its partners.
Results in brief
Final Activity Report Summary - HIV EC COMPLICATIONS (Role of poly (ADP-ribose) polymerase and oxidative stress in cardiovascular complications of HIV infection)
This project looked at the effects of HIV on the function of endothelial cells in the cardiovascular system which line the blood vessels, with an aim to understand how viral components of HIV and the drugs used to treat HIV cause cardiovascular disease. To this end we used model systems to assess cardiovascular cell function and studied how these cells may be protected from HIV-mediated damage. 1) The results from this project demonstrated that both vital components of HIV and anti-viral drugs used to treat HIV cause endothelial cell dysfunction. 2) The mechanism by which they damage the function of the endothelial cells is similar in that they overactivate a DNA repair enzyme, poly (ADP-ribose) polymerase, causing a catastrophic loss of cell energy and subsequent cell dysfunction. 3) Inhibitors of poly (ADP-ribose) polymerase proved effective in protecting against damage induced by both the viral proteins and anti-viral drugs. In the future, these inhibitor drugs may be a useful adjuvant therapy for HIV positive patients to reduce cardiovascular damage improving mortality and morbidity in these patients. 4) In addition we have identified oestrogen as the protective factor which reduces risk of cardiovascular dysfunction in female HIV patients. The mechanism of this protective action is oestrogen's ability to reduce poly (ADP-ribose) polymerase activity and hence maintain cell function. Overall this project has achieved increased understanding of what causes HIV patients to develop cardiovascular disease as well providing preliminary research into developing new therapies to prevent this.
Data: CORDIS, © European Union
Project objective
Recent research has lead to an increase in knowledge of the HIV virus and its mechanism of invading cells, which has lead to the development of effective therapies to retard the progression of the disease. This success has meant that HIV patients are livi ng longer and have become the fastest-growing cardiovascular disease population in the world. An understanding of the mechanisms involved and therapies for these HIV-induced cardiovascular problems are urgently required. This proposal examines the role o f oxidative stress and poly (ADP-ribose) activation in HIV envelope-protein mediated endothelial cell (EC) dysfunction. It determines whether therapies, developed to combat such activation, will be suitable for HIV-mediated cardiovascular disease. Specific ally, the aims of this project are (1) to investigate the effect of the HIV envelope proteins TAT and GP120 on vasorelaxation of ex vivo rat aortic rings in response to acetylcholine. Using specific inhibitors of oxidative stress, superoxide dismutase mime tics, and the PARP-specific enzyme inhibitor PJ-34, we will determine the extent of involvement of these pathways in vasculature dysfunction induced by HIV proteins. (2) We will also perform studies on isolated endothelial cells treated with HIV proteins t o determine specific cellular effects mediated by oxidative stress and PARP activation. The cellular effects to be investigated include viability, energetic status and expression of pro-inflammatory mediators. (3) We will use tissue from novel transgenic animals, including the PARP and NF-?ß knockout mouse, to further study the signalling pathways and possible intervention points in cardiovascular cells affected by HIV proteins. In conclusion, the data obtained from this proposal will greatly advance the knowledge about HIV-mediated cardiovascular dysfunction and possible therapies to combat this growing problem.
Original text from CORDIS.
Participants
- UNIVERSITY OF BRIGHTON · BRIGHTONCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union