MicroRNA-mediated vascular intercellular communication is altered in chronic kidney disease

Cardiovasc Res. 2022 Jan 7;118(1):316-333. doi: 10.1093/cvr/cvaa322.


Aims: Chronic kidney disease (CKD) is an independent risk factor for the development of coronary artery disease (CAD). For both, CKD and CAD, the intercellular transfer of microRNAs (miRs) through extracellular vesicles (EVs) is an important factor of disease development. Whether the combination of CAD and CKD affects endothelial function through cellular crosstalk of EV-incorporated miRs is still unknown.

Methods and results: Out of 172 screened CAD patients, 31 patients with CAD + CKD were identified and matched with 31 CAD patients without CKD. Additionally, 13 controls without CAD and CKD were included. Large EVs from CAD + CKD patients contained significantly lower levels of the vasculo-protective miR-130a-3p and miR-126-3p compared to CAD patients and controls. Flow cytometric analysis of plasma-derived EVs revealed significantly higher numbers of endothelial cell-derived EVs in CAD and CAD + CKD patients compared to controls. EVs from CAD + CKD patients impaired target human coronary artery endothelial cell (HCAEC) proliferation upon incubation in vitro. Consistent with the clinical data, treatment with the uraemia toxin indoxyl sulfate (IS)-reduced miR-130a-3p levels in HCAEC-derived EVs. EVs from IS-treated donor HCAECs-reduced proliferation and re-endothelialization in EV-recipient cells and induced an anti-angiogenic gene expression profile. In a mouse-experiment, intravenous treatment with EVs from IS-treated endothelial cells significantly impaired endothelial regeneration. On the molecular level, we found that IS leads to an up-regulation of the heterogenous nuclear ribonucleoprotein U (hnRNPU), which retains miR-130a-3p in the cell leading to reduced vesicular miR-130a-3p export and impaired EV-recipient cell proliferation.

Conclusion: Our findings suggest that EV-miR-mediated vascular intercellular communication is altered in patients with CAD and CKD, promoting CKD-induced endothelial dysfunction.

Keywords: Chronic kidney disease; Coronary artery disease; Extracellular vesicles; MicroRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Carotid Arteries / metabolism*
  • Carotid Arteries / pathology
  • Carotid Artery Injuries / genetics
  • Carotid Artery Injuries / metabolism*
  • Carotid Artery Injuries / pathology
  • Case-Control Studies
  • Cell Communication*
  • Cell Proliferation* / drug effects
  • Cells, Cultured
  • Coronary Artery Disease / genetics
  • Coronary Artery Disease / metabolism*
  • Coronary Artery Disease / pathology
  • Coronary Vessels / drug effects
  • Coronary Vessels / metabolism*
  • Coronary Vessels / pathology
  • Disease Models, Animal
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Extracellular Vesicles / drug effects
  • Extracellular Vesicles / genetics
  • Extracellular Vesicles / metabolism*
  • Extracellular Vesicles / pathology
  • Female
  • Humans
  • Indican / toxicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Renal Insufficiency, Chronic / genetics
  • Renal Insufficiency, Chronic / metabolism*
  • Renal Insufficiency, Chronic / pathology


  • MIRN130 microRNA, human
  • MIRN130 microRNA, mouse
  • MicroRNAs
  • Indican