Human Second Window Pre-Conditioning and Post-Conditioning by Nitrite Is Influenced by a Common Polymorphism in Mitochondrial Aldehyde Dehydrogenase.

Ormerod JO., Evans JD., Contractor H., Beretta M., Arif S., Fernandez BO., Feelisch M., Mayer B., Kharbanda RK., Frenneaux MP., Ashrafian H.

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 as ALDH2*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.

DOI

10.1016/j.jacbts.2016.11.006

Type

Journal article

Journal

JACC Basic Transl Sci

Publication Date

02/2017

Volume

2

Pages

13 - 21

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

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