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MicroRNA-765 influences arterial stiffness through modulating apelin expression
Yi-Chu Liao1, Yung-Song Wang2, Edward Hsi3
1Department of Neurology, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Rd., Taipei 112, Taiwan; Department of Neurology, National Yang-Ming University School of Medicine, No.155, Sec.2, Linong Street, Taipei 112, Taiwan.
Molecular and Cellular Endocrinology
|April 18, 2015
Summary
This study identifies a genetic link between a specific apelin gene (APLN) single nucleotide polymorphism (SNP) and arterial stiffness in women. This SNP influences APLN expression via miR-765, contributing to arterial stiffening.
Area of Science:
- Genetics
- Cardiovascular Biology
- Molecular Biology
Background:
- Arterial stiffness is a significant risk factor for cardiovascular diseases.
- The apelin gene (APLN) plays a role in vascular function.
- Genetic variations may influence susceptibility to arterial stiffness.
Purpose of the Study:
- To identify single nucleotide polymorphisms (SNPs) in the APLN gene associated with arterial stiffness.
- To elucidate the molecular mechanisms underlying this association.
Main Methods:
- A two-step genetic association study involving 1776 subjects.
- Genotyping of four APLN tagging SNPs.
- Reporter assays to assess SNP function and microRNA binding.
- In vitro experiments with endothelial cells to investigate signaling pathways.
Main Results:
- SNP rs3115757 showed a significant association with arterial stiffness parameters in women.
- SNP rs3115758, located in a miR-765 binding site, mediated the functional effect.
- miR-765 directly regulates APLN expression, impacting eNOS, ERK, Akt, and AMPK signaling.
Conclusions:
- The APLN genetic variant rs3115758 contributes to arterial stiffening susceptibility.
- This occurs through a mechanism involving miR-765-mediated repression of APLN expression.
- Findings highlight a novel genetic pathway influencing vascular health.
