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

oleh: Julian O.M. Ormerod, MD, PhD, Jonathan D.W. Evans, MD, Hussain Contractor, MD, PhD, Matteo Beretta, PhD, Sayqa Arif, MD, PhD, Bernadette O. Fernandez, PhD, Martin Feelisch, PhD, Bernd Mayer, PhD, Rajesh K. Kharbanda, MD, PhD, Michael P. Frenneaux, MD, Houman Ashrafian, MD, PhD

Format: Article
Diterbitkan: Elsevier 2017-02-01

Deskripsi

Summary: 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. Key Words: cytoprotection, endothelium, nitric oxide, nitrite, reperfusion injury