Lower Circulating Cell-Free Mitochondrial DNA Is Associated with Heart Failure in Type 2 Diabetes Mellitus Patients

Abstract

Cell-free nuclear (cf-nDNA) and mitochondrial (cf-mDNA) DNA are released from damaged cells in type 2 diabetes mellitus (T2DM) patients, contributing to adverse cardiac remodeling, vascular dysfunction, and inflammation. The purpose of this study was to correlate the presence and type of cf-DNAs with HF in T2DM patients. A total of 612 T2DM patients were prescreened by using a local database, and 240 patients (120 non-HF and 120 HF individuals) were ultimately selected. The collection of medical information, including both echocardiography and Doppler imagery, as well as the assessment of biochemistry parameters and the circulating biomarkers, were performed at baseline. The N-terminal brain natriuretic pro-peptide (NT-proBNP) and cf-nDNA/cf-mtDNA levels were measured via an ELISA kit and real-time quantitative PCR tests, respectively. We found that HF patients possessed significantly higher levels of cf-nDNA (9.9 ± 2.5 μmol/L vs. 5.4 ± 2.7 μmol/L; p = 0.04) and lower cf-mtDNA (15.7 ± 3.3 μmol/L vs. 30.4 ± 4.8 μmol/L; p = 0.001) than those without HF. The multivariate log regression showed that the discriminative potency of cf-nDNA >7.6 μmol/L (OR = 1.07; 95% CI = 1.03–1.12; p = 0.01) was higher that the NT-proBNP (odds ratio [OR] = 1.10; 95% confidence interval [CI] = 1.04–1.19; p = 0.001) for HF. In conclusion, we independently established that elevated levels of cf-nDNA, originating from NT-proBNP, were associated with HF in T2DM patients.

Exploring mitochondrial DNA copy number in circulating cell‐free DNA and extracellular vesicles across cardiovascular health status: A prospective case–control pilot study

“…While numerous studies have tested the associations between CVD and mtDNAcn from whole blood, there is a scarcity of data from human cohorts concerning ccf‐mtDNAcn in CVD. Berezina et al 67 . showed that heart failure patients ( N = 120) have higher ccf‐nDNAcn but lower ccf‐mtDNAcn than controls ( N = 120).…”

“…While numerous studies have tested the associations between CVD and mtDNAcn from whole blood, there is a scarcity of data from human cohorts concerning ccf-mtDNAcn in CVD. Berezina et al 67 showed that heart failure patients (N = 120) have higher ccf-nDNAcn but lower ccf-mtDNAcn than controls (N = 120). In contrast, Liu et al 24,68 measured an increase in mtDNA in diabetic patients with coronary heart disease (CHD) (N = 50) compared to those without CHD (N = 44).…”

Mitochondrial Fraction of Circulating Cell-Free DNA as an Indicator of Human Pathology

“…Rosa et al, found that increased ccf-mtDNA levels in diabetes were correlated with elevated cellular mtDNA levels [23]. Another study suggested that ccf-mtDNA could be evaluated as a biomarker of heart failure in patients with T2D [24]. Given these promising results, ccf-mtDNA could have clinical value in the management of diabetes.…”

Biomarkers of Atrial Fibrillation Recurrence in Patients with Paroxysmal or Persistent Atrial Fibrillation Following External Direct Current Electrical Cardioversion

“…Cell-free circulating DNA (cfcDNA) circulates in two main pools: circular and singlestranded molecules belonging to mitochondrial-derived and nuclear-derived subpopulations, reflecting patterns of DNA methylation and a variety of neutrophil extracellular traps (NETosis) [196,197]. The cfcDNA are determined in subdetectable concentrations under certain physiological conditions, such as physical exercise, whereas increased circulating levels of these fragments are strongly associated with cardiovascular, autoimmune, rheumatic diseases, infections, and malignancy [198][199][200][201][202]. The main causes of cfcDNA production are mitochondrial dysfunction and inflammation, which are powerful drivers of numerous diseases and conditions, including AF [203].…”