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

被引：5

作者：

Li, Kangbo ^{[1
,2
,3
]}

Dai, Mengjun ^{[1
,2
,3
]}

Sacirovic, Mesud ^{[1
]}

Zemmrich, Claudia ^{[4
]}

Pagonas, Nikolaos ^{[5
,6
]}

Ritter, Oliver ^{[5
,6
]}

Grisk, Olaf ^{[7
]}

Lubomirov, Lubomir T. ^{[7
]}

Lauxmann, Martin A. ^{[8
]}

Bramlage, Peter ^{[4
]}

Persson, Anja Bondke ^{[2
,3
]}

Buschmann, Eva ^{[9
]}

Buschmann, Ivo ^{[1
,6
]}

Hillmeister, Philipp ^{[1
,6
]}

机构：

[1] Univ Clin Brandenburg, Ctr Internal Med 1, Deutsch Angiol Zent Brandenburg Berlin, Brandenburg Med Sch Theodor Fontane,Dept Angiol, Brandenburg, Germany

[2] Free Univ Berlin, Charite Univmed Berlin, Berlin, Germany

[3] Humboldt Univ, Berlin, Germany

[4] Inst Pharmacol & Prevent Med, Cloppenburg, Germany

[5] Univ Clin Brandenburg, Ctr Internal Med 1, Brandenburg Med Sch Theodor Fontane, Dept Cardiol, Brandenburg, Germany

[6] Univ Potsdam, Joint Fac Brandenburg Univ Technol Cottbus Senften, Fac Hlth Sci Brandenburg, Brandenburg Med Sch Theodor Fontane, Brandenburg, Germany

[7] Inst Physiol, Brandenburg Med Sch Theodor Fontane, Neuruppin, Germany

[8] Inst Biochem, Brandenburg Med Sch Theodor Fontane, Brandenburg, Germany

[9] Univ Clin Graz, Dept Cardiol, Graz, Austria

来源：

FRONTIERS IN CARDIOVASCULAR MEDICINE | 2023年 / 10卷

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; PERIPHERAL ARTERY-DISEASE; FLOW-MEDIATED DILATION; NITRIC-OXIDE; DAMAGE RESPONSE; AGE; DYSFUNCTION; CELLS; RISK; ATTRITION; CANCER;

D O I：

10.3389/fcvm.2023.1157571

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

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 (beta = 0.229, P = 0.002) and leu-mtDNA (beta = 0.198, P = 0.008) were positively associated with FMD. In contrast, age was inversely associated with FMD (beta = -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.

引用

页数：11

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