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

Kangbo Li; Mengjun Dai; Mesud Sacirovic; Claudia Zemmrich; Nikolaos Pagonas; Oliver Ritter; Olaf Grisk; Lubomir T Lubomirov; Martin A Lauxmann; Peter Bramlage; Anja Bondke Persson; Eva Buschmann; Ivo Buschmann; Philipp Hillmeister

doi:10.3389/fcvm.2023.1157571

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

Front Cardiovasc Med. 2023 Jun 5:10:1157571. doi: 10.3389/fcvm.2023.1157571. eCollection 2023.

Authors

Kangbo Li^{1

2}, Mengjun Dai^{1

2}, Mesud Sacirovic¹, Claudia Zemmrich³, Nikolaos Pagonas^{4

5}, Oliver Ritter^{4

5}, Olaf Grisk⁶, Lubomir T Lubomirov⁶, Martin A Lauxmann⁷, Peter Bramlage³, Anja Bondke Persson², Eva Buschmann⁸, Ivo Buschmann^{1

5}, Philipp Hillmeister^{1

5}

Affiliations

¹ 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.
² Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
³ Institute for Pharmacology and Preventive Medicine, Cloppenburg, Germany.
⁴ Department for Cardiology, Center for Internal Medicine I, University Clinic Brandenburg, Brandenburg Medical School Theodor Fontane, Brandenburg an der Havel, Germany.
⁵ 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.
⁶ Institute of Physiology, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany.
⁷ Institute of Biochemistry, Brandenburg Medical School Theodor Fontane, Brandenburg an der Havel, Germany.
⁸ Department of Cardiology, University Clinic Graz, Graz, Austria.

Abstract

Background: We investigated the association between leukocyte telomere length, mitochondrial DNA copy number, and endothelial function in patients with aging-related cardiovascular disease (CVD).

Methods: In 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.

Results: cf-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).

Conclusion: TL positively correlates mtDNA-CN in both cfDNA and leuDNA. leu-TL and leu-mtDNA can be regarded as novel biomarkers of endothelial dysfunction.

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

Grants and funding

This work was supported by the Faculty of Health Sciences Brandenburg (Fakultät für Gesundheitswissenschaften Brandenburg, FGW). The open-access publishing was funded by the Brandenburg Medical School Theodor Fontane (Medizinische Hochschule Brandenburg Theodor Fontane, MHB) publication funding supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG).