John Pernow
The importance of erythrocytes as a mediator and treatment target in cardiovascular disease
We have identified that the red blood cell, a previously unstudied cell in this context, can cause cardiovascular damage in diabetes. The aim of the project is to identify the role of red blood cells in the development of early signs of atherosclerosis caused by common risk factors and myocardial damage in myocardial infarction, and to develop new treatments aimed at changing the function of the red blood cells and thus preventing the onset of atherosclerosis and infarction damage. The studies will improve our understanding of the causes of early atherosclerosis, cardiovascular complications in diabetes and myocardial damage in heart attacks. The results may lead to new treatment options to prevent cardiovascular complications in diabetes and myocardial damage in heart attacks.
Selected publications
Yang J, Sundqvist ML, Zheng X, Jiao T, Collado A, Tratsiakovich Y, Mahdi A, Tengbom J, Mergia E, Catrina S-B, Zhou Z, Carlström M, Akaike T, Cortese-Krott MM, Weitzberg E, Lundberg JO, Pernow J. Hypoxic erythrocytes mediate cardioprotection through activation of soluble guanylate cyclase and release of cyclic GMP. J Clin Invest. 2023 Sep 1;133(17):e167693.
Jiao, T, Collado, A, Mahdi, A, Tengbom, J, Tratsiakovich, Y, Milne, GT, Alvarsson, M. Lundberg, JON, Zhou, Z, Yang, J, Pernow J. Stimulation of erythrocyte soluble guanylyl cyclase induces cGMP export and cardioprotection in type 2 diabetes. JACC Basic Transl Sci, 2023;8:907-918.
Zhou Z, Collado A, Sun, Tratsiakovich Y, Mahdi A, Winter H, Chernogubova E, Seime T, Narayanan S, Jiao T, Jin H, Alvarsson M, Zheng X, Yang J, Hedin U, Catrina S-B, Maegdefessel L, Pernow J. Downregulation of erythrocyte miR-210 induces endothelial dysfunction in type 2 diabetes. Diabetes. 2022 Feb 1;71(2):285-297.
Zhou ZC, Mahdi A, Tratsiakovich Y, Zahorán S, Kovamees O, Nordin F, Uribe Gonzalez AE, Alvarsson M, Östenson C-G, Andersson DC, Hedin U, Hermesz E, Lundberg JO, Yang JN, Pernow J. Red blood cells from patients with type 2 diabetes induce endothelial dysfunction via arginase I. J Am Coll Cardiol. 2018;72:769-780.
Yang J, Gonon AT, Sjöquist PO, Lundberg JON, Pernow J. Arginase regulates red blood cell nitric oxide synthase and export of cardioprotective nitric oxide bioactivity. Proc Natl Acad Sci U A. 2013 Sep 10;110(37):15049-54.