PMID- 36755219
OWN - NLM
STAT- MEDLINE
DCOM- 20230210
LR  - 20230211
IS  - 1471-2261 (Electronic)
IS  - 1471-2261 (Linking)
VI  - 23
IP  - 1
DP  - 2023 Feb 8
TI  - Association of circulating MtDNA with CVD in hemodialysis patients and in vitro 
      effect of exogenous MtDNA on cardiac microvascular inflammation.
PG  - 74
LID - 10.1186/s12872-023-03104-2 [doi]
LID - 74
AB  - BACKGROUND: Chronic kidney disease (CKD) patients sustain a fairly high 
      prevalence of cardiovascular disease (CVD). Microvascular inflammation is an 
      early manifestation of CVD, and the released mitochondrial DNA (MtDNA) has been 
      proposed to be a crucial integrator of inflammatory signals. Herein, the aim of 
      this study was to determine the relationship between CVD, microvessel, and 
      circulating MtDNA in the settings of uremia. METHODS: Forty-two maintenance 
      hemodialysis (MHD) patients and 36 health controls were enrolled in this study. 
      Plasma cell-free MtDNA was detected by TaqMan-based qPCR assay. CVD risk markers 
      including high-sensitive C-reactive protein (Hs-CRP), monocyte chemoattractant 
      protein-1 (MCP-1), fibrinogen, and erythrocyte sedimentation rate (ESR) were 
      measured by standard assays. Ten-year CVD risk was calculated from the Framingham 
      risk score (FRS) model. In vitro study, human cardiac microvascular endothelial 
      cells (HCMECs) were incubated with normal or uremic serum, with or without 
      exogenous MtDNA. Intracellular toll-like receptor 9 (TLR9), adhesion molecule 1 
      (ICAM-1), MCP-1 and tumor necrosis factor-alpha (TNF-alpha) and cytosolic MtDNA were 
      detected by qPCR. RESULTS: Plasma MtDNA in MHD patients was significantly higher 
      than healthy controls (4.74 vs. 2.41 x 10(5) copies/mL; p = 0.000). Subsequently, 
      the MHD patients were classified into two groups based on the MtDNA median 
      (4.34 x 10(5) copies/mL). In stratified analyses, the levels of Hs-CRP (5.02 vs. 
      3.73 mg/L; p = 0.042) and MCP-l (99.97 vs. 64.72 pg/mL; p = 0.008) and FRS (21.80 
      vs. 16.52; p = 0.016) in the high plasma MtDNA group were higher than those in 
      the low plasma MtDNA group. In vitro study, we found that exogenous MtDNA 
      aggravated uremic serum-induced microvascular inflammation (ICAM-1 and TNF-alpha) in 
      HCMECs (all p < 0.05). Besides, the addition of MtDNA to the medium resulted in a 
      further increase in cytosolic MtDNA and TLR9 levels in uremic serum-treated cells 
      (all p < 0.05). In patients with MHD, MtDNA levels in plasma were significantly 
      reduced after a single routine hemodialysis (pre 4.47 vs. post 
      3.45 x 10(5) copies/mL; p = 0.001) or hemodiafiltration (pre 4.85 vs. post 
      4.09 x 10(5) copies/mL; p = 0.001). These two approaches seem similar in terms of 
      MtDNA clearance rate (21.26% vs. 11.94%; p = 0.172). CONCLUSIONS: Overall, the 
      present study suggests that MtDNA released into the circulation under the uremic 
      toxin environment may adversely affect the cardiovascular system by exacerbating 
      microvascular inflammation, and that reducing circulating MtDNA might be a future 
      therapeutic strategy for the prevention of MHD-related CVD.
CI  - (c) 2023. The Author(s).
FAU - Fan, Zhen
AU  - Fan Z
AD  - Department of Geriatrics, Sichuan Provincial People's Hospital, University of 
      Electronic Science and Technology of China, Chengdu, Sichuan, China.
FAU - Feng, Ya
AU  - Feng Y
AD  - Department of Nephrology, Clinical Medical College, The First Affiliated Hospital 
      of Chengdu Medical College, Chengdu, Sichuan, China.
FAU - Zang, Li
AU  - Zang L
AD  - Department of Nephrology, Clinical Medical College, The First Affiliated Hospital 
      of Chengdu Medical College, Chengdu, Sichuan, China.
FAU - Guo, Yi
AU  - Guo Y
AD  - Department of Neurology, Sichuan Provincial People's Hospital, University of 
      Electronic Science and Technology of China, No. 32, West Section 2, Yihuan Road, 
      Qingyang District, Chengdu, 610072, Sichuan, China. 419535941@qq.com.
FAU - Zhong, Xiao-Yi
AU  - Zhong XY
AD  - Department of Nephrology, Xinqiao Hospital, Army Medical University (Third 
      Military Medical University), No. 83 Xinqiao Zhengjie, Shapingba District, 
      Chongqing, 400037, China. zhongxy729@163.com.
LA  - eng
GR  - 2022NSFSC1387/Natural Science Foundation of Sichuan Province/
GR  - 2021QN2/Talent Youth Fund of Sichuan Provincial People's Hospital/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230208
PL  - England
TA  - BMC Cardiovasc Disord
JT  - BMC cardiovascular disorders
JID - 100968539
RN  - 9007-41-4 (C-Reactive Protein)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 0 (Toll-Like Receptor 9)
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Biomarkers)
SB  - IM
MH  - Humans
MH  - *Cardiovascular Diseases/diagnosis/genetics
MH  - C-Reactive Protein
MH  - Intercellular Adhesion Molecule-1
MH  - Toll-Like Receptor 9
MH  - DNA, Mitochondrial/genetics
MH  - Tumor Necrosis Factor-alpha
MH  - Endothelial Cells
MH  - Renal Dialysis/adverse effects
MH  - Inflammation
MH  - Arrhythmias, Cardiac/etiology
MH  - Biomarkers
PMC - PMC9906832
OTO - NOTNLM
OT  - Cardiac microvascular endothelial cells
OT  - Cardiovascular disease
OT  - Inflammation
OT  - Maintenance hemodialysis
OT  - Mitochondrial DNA
COIS- All authors declare having no competing interests.
EDAT- 2023/02/10 06:00
MHDA- 2023/02/11 06:00
PMCR- 2023/02/08
CRDT- 2023/02/09 00:19
PHST- 2022/09/12 00:00 [received]
PHST- 2023/02/01 00:00 [accepted]
PHST- 2023/02/09 00:19 [entrez]
PHST- 2023/02/10 06:00 [pubmed]
PHST- 2023/02/11 06:00 [medline]
PHST- 2023/02/08 00:00 [pmc-release]
AID - 10.1186/s12872-023-03104-2 [pii]
AID - 3104 [pii]
AID - 10.1186/s12872-023-03104-2 [doi]
PST - epublish
SO  - BMC Cardiovasc Disord. 2023 Feb 8;23(1):74. doi: 10.1186/s12872-023-03104-2.