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MiR-15b-5p Regulates Collateral Artery Formation by Targeting AKT3 (Protein Kinase B-3)

Ling-Ping Zhu1, Ji-Peng Zhou1, Jia-Xiong Zhang1

  • 1From the Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China (L.-P.Z., J.-P.Z., J.-Y.W., Z.-Y.W., M.P., L.-F.L., L.C., G.-G.Z.); Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, China (J.-X.Z., C.-C.L., Y.-P.B.); and Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, China (K.-K.W.).

Arteriosclerosis, Thrombosis, and Vascular Biology
|March 4, 2017
PubMed
Abstract

Insights

Low expression of microRNA-15b-5p (miR-15b-5p) indicates good coronary collateral artery function. This microRNA regulates blood vessel formation and may be a therapeutic target for ischemic diseases.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Vascular Biology

Background:

  • Coronary heart disease (CHD) severity correlates with collateral artery development.
  • Identifying biomarkers for collateral function is crucial for patient stratification.
  • MicroRNAs (miRNAs) play roles in vascular homeostasis and disease.

Purpose of the Study:

  • To identify circulating miRNAs associated with coronary collateral artery function in severe CHD.
  • To elucidate the in vivo and in vitro mechanisms of action of identified miRNAs.
  • To explore potential therapeutic applications of these miRNAs in ischemic conditions.

Main Methods:

  • Circulating miRNA expression profiling in CHD patients.
  • Murine hindlimb ischemia model for in vivo studies.
  • In situ hybridization, cell migration, and proliferation assays for in vitro analysis.
  • Identification of miRNA targets using molecular biology techniques.

Main Results:

  • miR-15b-5p was identified as a circulating miRNA with low expression in patients with sufficient collateral artery function.
  • In vivo, miR-15b-5p expression was downregulated after femoral artery ligation, and its overexpression inhibited arteriogenesis and angiogenesis.
  • In vitro, miR-15b-5p modulated endothelial cell migration and proliferation, targeting AKT3 (protein kinase B-3).
  • AKT3 deficiency suppressed arteriogenesis and blood perfusion recovery in mice.

Conclusions:

  • Circulating miR-15b-5p serves as a biomarker for differentiating collateral artery development in CHD.
  • miR-15b-5p is a key regulator of arteriogenesis and angiogenesis.
  • miR-15b-5p represents a potential therapeutic target for ischemic diseases.
Keywords:
AKT3arteriogenesiscollateral circulationhindlimb ischemiamiR-15b-5p

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