Decoding of miR-7-5p in Colony Forming Unit-Hill Colonies as a Biomarker of Subclinical Cardiovascular Disease-A...

Area of Science:

• Biochemistry
• Molecular Biology
• Cardiovascular Research

Background:

• Colony forming unit-Hill (CFU-Hill) colonies are emerging biomarkers for vascular health.
• Overexpression of microRNA-7-5p (miR-7-5p) is implicated in atherosclerosis and cardiovascular disease (CVD) risk in animal models.

Purpose of the Study:

• To investigate the role of miR-7-5p expression in CFU-Hill colonies in type 1 diabetes mellitus (T1DM).
• To evaluate the effect of metformin on miR-7-5p levels and subclinical CVD in T1DM patients.

Main Methods:

• Measured miR-7-5p expression in CFU-Hill colonies from T1DM patients and healthy controls (HC).
• Administered metformin to T1DM subjects for eight weeks and reassessed miR-7-5p levels.
• Correlated miR-7-5p with inflammatory markers and used ROC curve analysis for CVD biomarker potential.
• Performed Ingenuity Pathway Analysis to predict molecular targets of miR-7-5p and metformin.

Main Results:

• miR-7-5p was significantly upregulated in T1DM patients compared to HC.
• Metformin treatment reduced miR-7-5p levels in T1DM patients to those observed in HC.
• miR-7-5p showed positive correlations with c-reactive protein and C-X-C motif chemokine ligand 10.
• Upregulated miR-7-5p identified subclinical CVD in T1DM patients with HbA1c ≥ 44.3 mmol/mol.
• Pathway analysis suggested miR-7-5p inhibits key pro-atherogenic genes, while metformin activates them via TGF-β1/Smad2/3 signaling.

Conclusions:

• miR-7-5p is a pro-atherogenic molecule and a potential prognostic biomarker for subclinical CVD in T1DM.
• Metformin effectively reduces miR-7-5p levels in T1DM, highlighting a potential therapeutic mechanism.
• CFU-Hill colonies and miR-7-5p expression offer a novel approach for assessing vascular health and CVD risk in T1DM.