Cellular and molecular biomedicine
Aston Research Centre for Healthy Ageing (ARCHA) Aston Research centre in CHildren and Young people's health(ARCHY)
Professor Ahmed’s laboratory was amongst the first laboratories to signal the importance of vascular growth factors in pregnancy and pioneered the concept of angiogenic imbalance theory in preeclampsia in the mid 1990s.
In 2000, he discovered that the enzyme placental heme oxygenase (HO) protects the human placenta against injury (Mol Med. 6:391-409, 2000) and went on to identify carbon monoxide (CO), the gaseous product of HO, as an inhibitor of anti-angiogenic proteins (soluble Flt-1 and soluble endoglin) (Circulation 115:1789-97, 2007; Natural Protein Offers New Therapeutic Potential for Pre-Eclampsia). Soluble Flt-1, the natural anti-VEGF factor in circulation, is increasingly recognized as a major factor responsible for the clinical signs of preeclampsia. Ahmed identified soluble Flt-1 as the single most important molecule responsible for angiogenic imbalance in preeclampsia by demonstrating that the removal of sFlt-1 from preeclamptic samples restored angiogenic balance (Ahmad and Ahmed Circ Res 95:884-91,2004) which was confirmed in vivo in women by others.
The identification that increasing HO activity could provide protection against preeclampsia formed the basis for the world’s first randomized controlled clinical trial on statins in pregnancy StAmP Trial (see: Heart disease drugs could treat pregnant women; Heart drugs used in pre-eclampsia pregnancy trial).
Recently his laboratory at Aston University has identified another diatomic molecule, hydrogen sulfide (H2S), which offers potential to treat both preeclampsia and fetal growth restriction in pregnancy. The new finding is published in Circulation. This work was recently highlighted as being a “groundbreaking study” by Circulation and within the media (see: Breakthrough in fight against pre-eclampsia). This is the first time two naturally-occurring small gaseous molecules (CO and H2S) have been shown to prevent the release of the culprit proteins (sFlt-1 and sEng), which are elevated in preeclampsia. More importantly, in this new work they show that they can restore fetal growth and fix the vascular abnormalities (angiogenesis) in the placenta by giving back hydrogen sulfide. Before this decade is out, Aston’s team may have a treatment for preeclampsia, a special maternal hypertensive condition that has eluded science.
Ahmed has an international reputation in angiogenesis and vascular protection. He was Chair of the Organising Committee for 7th International Congress on Heme Oxygenases and Related Enzymes. His research impact is self-evident. Based on his discoveries, two additional international clinical trials have been initiated (details here and here) and he held a Visiting Professorship at the world-renowned Stanford University, where he regularly visits.
Wang K, Ahmad S, Cai M, Rennie J, Fujisawa T, Crispi F, Baily J, Miller MJ, Cudmore MJ, Hadoke PWF, Wang R, Gratacós E, Buhimschi IA, Buhimschi CS, and Ahmed A. (2013) Dysregulation of hydrogen sulfide (H2S) producing enzyme cystathionine ?-lyase (CSE) contributes to maternal hypertension and placental abnormalities in preeclampsia. Circulation (in press).
Cudmore MJ, Hewett PW, Ahmad S, Wang KQ, Cai M, Al-Ani B, Fujisawa T, Sissaoui S, Ramma W, Miller M, Newby DE, Gu Y, Barleon B, Weich H and Ahmed A. (2012) Identification and functional characterisation of VEGF-A receptor heterodimerisation. Nat Comms3:972. doi: 10.1038/ncomms1977.
Cudmore MJ, Ahmad S, Sissaoui S, Ramma W, Ma B, Fujisawa T, Al-Ani B, Wang K, Cai M, Crispi F, Hewett PW, Gratacós E, Egginton S and Ahmed A. (2012) Loss of Akt activity increases circulating soluble endoglin release in preeclampsia: identification of inter-dependency between Akt-1 and heme oxygenase-1. Eur Heart J 33:1150-8.
Rosenberg VA, Buhimschi IA, Lockwood CJ, Paidas MJ, Dulay AT, Ramma W, Abdel-Razeq SS, Zhao G, Ahmad S, Ahmed A, Buhimschi CS. (2011). Heparin elevates circulating soluble Fms-Like Tyrosine immunoreactivity in pregnant women receiving anticoagulation therapy. Circulation 124(23):2543-53.
Crispi F, Bijnens B, Figueras F, Bartrons J, Eixarch E, Le Noble F, Ahmed A, Gratacós E. (2010) Fetal growth restriction results in remodeled and less efficient hearts in children. Circulation 121(22):2427-36.
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