MiR-20b-5p involves in vascular aging induced by hyperhomocysteinemia

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• Genomics

Background:

• Hyperhomocysteinemia (HHcy) is a risk factor for atherosclerosis (AS).
• Homocysteine (Hcy) promotes endothelial cell senescence, contributing to AS.
• MicroRNAs (miRNAs) are implicated in HHcy pathophysiology, but their role in arterial miRNA-mRNA networks in HHcy is understudied.

Purpose of the Study:

• To investigate miRNA and mRNA expression changes in the arteries of HHcy model mice.
• To identify specific miRNA-mRNA interactions involved in HHcy-induced endothelial cell senescence.
• To elucidate the role of miR-20b-5p in HHcy-related endothelial dysfunction.

Main Methods:

• RNA-sequencing to analyze miRNA and mRNA expression in HHcy mouse arteries.
• Bioinformatic tools (TargetScan, miRDB) for miRNA-mRNA pair prediction.
• In vitro experiments using HHcy human umbilical vein endothelial cells (HUVECs) to validate targets and assess cellular senescence markers.

Main Results:

• Significant differential expression of 216 mRNAs and 48 miRNAs identified.
• 29 miRNA-mRNA pairs predicted, with miR-20b-5p and FJX1 showing high interaction potential.
• miR-20b-5p inhibition upregulated FJX1 in HHcy HUVECs; HHcy induced senescence markers (ROS, SA-β-gal, p16, p21), which were reversed by miR-20b-5p inhibition.

Conclusions:

• HHcy significantly alters arterial miRNA and mRNA expression profiles.
• miR-20b-5p plays a crucial role in HHcy-induced endothelial cell senescence.
• Targeting miR-20b-5p may offer a therapeutic strategy for HHcy-related vascular complications.