Decreased microRNA is involved in the vascular remodeling abnormalities in chronic kidney disease (CKD)

Area of Science:

• Cardiovascular Biology
• Nephrology
• Molecular Biology

Background:

• Chronic kidney disease (CKD) is associated with vascular remodeling, a significant risk factor for cardiovascular disease.
• MicroRNAs (miRNAs) are critical regulators of gene expression and are implicated in vascular smooth muscle cell (VSMC) function.

Purpose of the Study:

• To investigate the role of specific vascular miRNAs (miR-125b, miR-145, miR-155) in patients with CKD and in a rat model.
• To explore the mechanisms underlying altered miRNA expression in CKD-related vascular dysfunction.

Main Methods:

• Measurement of circulating miR-125b, miR-145, and miR-155 levels in 90 CKD patients and correlation with estimated glomerular filtration rate (eGFR).
• Analysis of aortic miRNA expression and target genes (RUNX2, AT1R, myocardin) in CKD rats.
• In vitro studies using primary VSMCs from CKD rats to examine miRNA regulation and functional effects of miR-155.

Main Results:

• Decreased circulating levels of miR-125b, miR-145, and miR-155 were observed in CKD patients, correlating with reduced eGFR.
• Aortic expression of these miRNAs was decreased in CKD rats, with altered expression of their target genes.
• miR-155 expression negatively correlated with aortic calcification in CKD rats.
• Intracellular miRNA processing machinery (DROSHA, DICER) was not altered in CKD VSMCs.
• Overexpression of miR-155 in CKD rat VSMCs reduced angiotensin II type I receptor (AT1R) expression and cellular proliferation.

Conclusions:

• CKD is associated with decreased expression of vascular miRNAs (miR-125b, miR-145, miR-155) in both patients and a rat model.
• These miRNA alterations may contribute to VSMC dysfunction and vascular remodeling in CKD.
• Reduced circulating miRNA levels might reflect decreased vascular release, warranting further investigation.