ALKBH1 reduces DNA N⁶-methyladenine to allow for vascular calcification in chronic kidney disease

Vascular calcification is a common complication of chronic kidney disease (CKD), and one of the main risk factors for increased cardiovascular morbidity and mortality in patients with CKD. In this issue of the JCI, Ouyang and Su et al. report that Alkb homolog 1 (ALKBH1), a DNA demethylase, reduced DNA N⁶-methyladenine (6mA) in vascular smooth muscle cells (VSMCs) and leukocytes, thus leading to aortic arch calcification in the patients with CKD. During the progression of vascular calcification, increased ALKBH1 expression was linked to decreased 6mA levels, findings that the authors noted in both patients with CKD and CKD mouse models. The kidney and vascular disease risk factor soluble urokinase receptor (suPAR) was also elevated in the plasma. Notably, lower 6mA levels induced BMP2-mediated osteogenic reprogramming in the VSMCs. These findings present a function of ALKBH1 in vascular calcification and provide a framework for therapeutic strategies.