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.
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.