title: Human Second Window Pre-Conditioning and Post-Conditioning by Nitrite Is Influenced by a Common Polymorphism in Mitochondrial Aldehyde Dehydrogenase.
abstract: Pre-conditioning is an exciting physiological phenomenon that, despite great efforts, has so far resisted translation to mainstream clinical medicine. Many potential triggers (e.g., ischemia of the organ in question or a remote organ, many different drugs) have been investigated, but recent work has implicated activation of mitochondrial aldehyde dehydrogenase (ALDH2) as central to the process. A genetic polymorphism, known asALDH2*2, is common worldwide (present in up to 40% of Han Chinese people) and produces a functionally different enzyme. The authors used a variety of protocols in the human ischemic forearm model, in participants with both enzyme types, to assess cytoprotection with low-dose sodium nitrite and attempt to further elucidate the role of ALDH2.
authors.affiliation: Oxford Heart Centre, Oxford University Hospitals, Oxford, United Kingdom.
authors.forename: Julian O M
authors.initials: JO
authors.lastname: Ormerod
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
authors.forename: Jonathan D W
authors.initials: JD
authors.lastname: Evans
authors.affiliation: Department of Cardiovascular Medicine, West Wing, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Hussain
authors.initials: H
authors.lastname: Contractor
authors.affiliation: Department of Pharmacology and Toxicology, Karl-Franzens-Universität, Graz, Austria.
authors.forename: Matteo
authors.initials: M
authors.lastname: Beretta
authors.affiliation: Department of Cardiovascular Medicine, Medical School, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Sayqa
authors.initials: S
authors.lastname: Arif
authors.affiliation: Faculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: Bernadette O
authors.initials: BO
authors.lastname: Fernandez
authors.affiliation: Faculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Feelisch
authors.affiliation: Department of Pharmacology and Toxicology, Karl-Franzens-Universität, Graz, Austria.
authors.forename: Bernd
authors.initials: B
authors.lastname: Mayer
authors.affiliation: Oxford Heart Centre, Oxford University Hospitals, Oxford, United Kingdom.
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Kharbanda
authors.affiliation: Medical School, University of East Anglia, Norwich, United Kingdom.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Frenneaux
authors.affiliation: Department of Cardiovascular Medicine, West Wing, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Houman
authors.initials: H
authors.lastname: Ashrafian
keywords: ALDH2, mitochondrial aldehyde dehydrogenase; Ach, acetylcholine; FBF, forearm blood flow; FBF-R, forearm blood flow ratio; GTN, glyceryl trinitrate; IR, ischemia–reperfusion; RIPC, remote ischemic pre-conditioning; cytoprotection; endothelium; nitric oxide; nitrite; reperfusion injury