Leukocyte telomere length and mitochondrial DNA copy number associate with endothelial function in aging-related cardiovascular disease

Frontiers in Cardiovascular Medicine

Cardiovascular Medicine

Anja Bondke Persson¹  Mesud Sacirovic²  Kangbo Li³  Mengjun Dai³  Ivo Buschmann⁴  Philipp Hillmeister⁴  Nikolaos Pagonas⁵  Oliver Ritter⁵  Eva Buschmann⁶  Claudia Zemmrich⁷  Peter Bramlage⁷  Martin A. Lauxmann⁸  Lubomir T. Lubomirov⁹  Olaf Grisk⁹ 

[1] Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany;Department for Angiology, Center for Internal Medicine I, Deutsches Angiologie Zentrum Brandenburg - Berlin, University Clinic Brandenburg, Brandenburg Medical School Theodor Fontane, Brandenburg an der Havel, Germany;Department for Angiology, Center for Internal Medicine I, Deutsches Angiologie Zentrum Brandenburg - Berlin, University Clinic Brandenburg, Brandenburg Medical School Theodor Fontane, Brandenburg an der Havel, Germany;Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany;Department for Angiology, Center for Internal Medicine I, Deutsches Angiologie Zentrum Brandenburg - Berlin, University Clinic Brandenburg, Brandenburg Medical School Theodor Fontane, Brandenburg an der Havel, Germany;Faculty of Health Sciences Brandenburg, Joint Faculty of the Brandenburg University of Technology Cottbus – Senftenberg, The Brandenburg Medical School Theodor Fontane, University of Potsdam, Brandenburg an der Havel, Germany;Department for Cardiology, Center for Internal Medicine I, University Clinic Brandenburg, Brandenburg Medical School Theodor Fontane, Brandenburg an der Havel, Germany;Faculty of Health Sciences Brandenburg, Joint Faculty of the Brandenburg University of Technology Cottbus – Senftenberg, The Brandenburg Medical School Theodor Fontane, University of Potsdam, Brandenburg an der Havel, Germany;Department of Cardiology, University Clinic Graz, Graz, Austria;Institute for Pharmacology and Preventive Medicine, Cloppenburg, Germany;Institute of Biochemistry, Brandenburg Medical School Theodor Fontane, Brandenburg an der Havel, Germany;Institute of Physiology, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany;

关键词: telomere length;    mitochondrial DNA copy number;    endothelial function;    flow-mediated dilation;    peripheral blood mononuclear cells;    cell-free DNA;    aging-related cardiovascular disease;   

DOI  :  10.3389/fcvm.2023.1157571

 received in 2023-02-02, accepted in 2023-03-22,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundWe investigated the association between leukocyte telomere length, mitochondrial DNA copy number, and endothelial function in patients with aging-related cardiovascular disease (CVD).MethodsIn total 430 patients with CVD and healthy persons were enrolled in the current study. Peripheral blood was drawn by routine venipuncture procedure. Plasma and peripheral blood mononuclear cells (PBMCs) were collected. Cell-free genomic DNA (cfDNA) and leukocytic genomic DNA (leuDNA) were extracted from plasma and PBMCs, respectively. Relative telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) were analyzed using quantitative polymerase chain reaction. Endothelial function was evaluated by measuring flow-mediated dilation (FMD). The correlation between TL of cfDNA (cf-TL), mtDNA-CN of cfDNA (cf-mtDNA), TL of leuDNA (leu-TL), mtDNA-CN of leuDNA (leu-mtDNA), age, and FMD were analyzed based on Spearman's rank correlation. The association between cf-TL, cf-mtDNA, leu-TL, leu-mtDNA, age, gender, and FMD were explored using multiple linear regression analysis.Resultscf-TL positively correlated with cf-mtDNA (r = 0.1834, P = 0.0273), and leu-TL positively correlated with leu-mtDNA (r = 0.1244, P = 0.0109). In addition, both leu-TL (r = 0.1489, P = 0.0022) and leu-mtDNA (r = 0.1929, P < 0.0001) positively correlated with FMD. In a multiple linear regression analysis model, both leu-TL (β = 0.229, P = 0.002) and leu-mtDNA (β = 0.198, P = 0.008) were positively associated with FMD. In contrast, age was inversely associated with FMD (β = −0.426, P < 0.0001).ConclusionTL positively correlates mtDNA-CN in both cfDNA and leuDNA. leu-TL and leu-mtDNA can be regarded as novel biomarkers of endothelial dysfunction.

【 授权许可】

Unknown   
© 2023 Li, Dai, Sacirovic, Zemmrich, Pagonas, Ritter, Grisk, Lubomirov, Lauxmann, Bramlage, Persson, Buschmann, Buschmann and Hillmeister.