Mechanisms
Blocking microRNA-221-3p restores angiogenesis in Lp(a)-injured endothelial progenitor cells via a SIRT1-RAF/MEK/ERK pathway (Mol Med Rep 2024)
Original title: Downregulation of microRNA‑221‑3p promotes angiogenesis of lipoprotein(a)‑injured endothelial progenitor cells by targeting silent information regulator 1 to activate the RAF/MEK/ERK signaling pathway
In this in vitro study, treating endothelial progenitor cells (EPCs) with Lp(a) reduced their proliferation, migration, adhesion and angiogenic capacity while increasing apoptosis. Transfection with a microRNA (miR)-221-3p inhibitor weakened these harmful effects of Lp(a), and separately, overexpressing silent information regulator 1 (SIRT1) also weakened Lp(a)'s negative effects on EPCs, an effect blocked by inhibiting the RAF/MEK/ERK signalling pathway. Dual-luciferase reporter assays confirmed SIRT1 as a direct target of miR-221-3p. The findings identify a miR-221-3p to SIRT1 to RAF/MEK/ERK axis through which Lp(a) impairs EPC function and angiogenesis, suggesting miR-221-3p inhibition or SIRT1 activation as candidate strategies to counter Lp(a)-mediated vascular injury, though this remains a cell-culture finding without in vivo validation.
Original abstract
The present study aimed to investigate the role of microRNA (miR)‑221‑3p in endothelial progenitor cells (EPCs) treated with lipoprotein(a) [LP(a)]. EPCs were identified using immunofluorescence assays and miR‑221‑3p levels were measured using reverse transcription‑quantitative PCR. EPC migration was detected using Transwell assays, proliferation was measured by staining with 5‑ethynyl‑2'‑deoxyuridine and adhesion was assessed by microscopy. Flow cytometry was used to measure apoptosis and protein expression was detected using western blotting. A dual‑luciferase reporter assay was used to confirm the target interactions. The proliferation, migration, adhesion and angiogenesis of EPCs were decreased, and apoptosis was increased after treatment with LP(a). These effects were weakened by transfection with miR‑221‑3p inhibitor. The negative effects of LP(a) on EPCs were also weakened by overexpression of silent information regulator 1 (SIRT1). Inhibition of the RAF/MEK/ERK signaling pathway blocked the effects of SIRT1 overexpression. In conclusion, miR‑221‑3p inhibitor transfection activated the RAF/MEK/ERK signaling pathway through SIRT1, promoted the proliferation, migration, adhesion and angiogenesis of EPCs, and reduced apoptosis.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.