Association of Circulating MtDNA With CVD in Hemodialysis Patients and In Vitro Effect of Exogenous MtDNA on Cardiac Microvascular Inflammation

Authors

Zhen Fan
Ya Feng
Li Zang
Yi Guo
Xiao-Yi Zhong

Publication Date

2-8-2023

Journal

BMC Cardiovascular Disorders

Abstract

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-α (TNF-α) and cytosolic MtDNA were detected by qPCR.

RESULTS: Plasma MtDNA in MHD patients was significantly higher than healthy controls (4.74 vs. 2.41 × 10

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.

Keywords

Maintenance hemodialysis, Cardiovascular disease, Cardiac microvascular endothelial cells, Mitochondrial DNA, Inflammation