miR-144 targets in myocardial hypertrophy and coronary microvascular dysfunction in hypertrophic cardiomyopathy:

Maria Lombardi1, Monica Barki2, Lucia Spartano1

  • 1Cardiovascular Research Center, IRCCS San Raffaele Hospital, Via Olgettina, 60, 20132, Milan, Italy.

PubMed

Insights

MicroRNA-144-3p (miR-144) is downregulated in hypertrophic cardiomyopathy (HCM), impacting cardiac remodeling and coronary microvascular dysfunction (CMD). Its dysregulation suggests a dual role in HCM pathogenesis.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Genetics

Background:

  • Hypertrophic cardiomyopathy (HCM) involves left ventricular hypertrophy, diastolic dysfunction, and coronary microvascular dysfunction (CMD).
  • MicroRNA-144-3p (miR-144) is implicated in HCM pathophysiology.
  • This study explores miR-144's role in HCM, focusing on cardiac remodeling and CMD.

Purpose of the Study:

  • Investigate the relationship between miR-144, its target genes, and phenotypic features of cardiac remodeling and CMD in obstructive HCM.
  • Analyze miR-144 expression in cardiomyocytes and arterioles.
  • Assess the correlation between miR-144 levels and clinical parameters.

Main Methods:

  • Integrated molecular data (RT-qPCR, ELISA, Western blot) with echocardiography (ECHO) and cardiac magnetic resonance (CMR).
  • Laser capture microdissection to isolate cardiomyocyte and arteriole areas for miR-144 analysis.
  • Quantified expression of miR-144 and its target genes (EZH2, mTOR, VEGF-A, etc.).

Main Results:

  • Downregulated miR-144 in HCM myocardium correlated with restrictive physiology and negative atrial remodeling.
  • Upregulated miR-144 target genes (mTOR, EZH2) in arterioles linked to hypertrophy and diastolic dysfunction.
  • Evidence of inefficient translation and impaired myocardial relaxation, suggesting CMD.

Conclusions:

  • miR-144 may act as a molecular regulator in HCM.
  • Findings suggest a dual role for miR-144 in both cardiac hypertrophy and CMD.
  • miR-144 dysregulation contributes to HCM pathophysiology.
Abstract

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