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Dysregulation of the calcium handling protein, CCDC47, is associated with diabetic cardiomyopathy

Khampaseuth Thapa1, Kai Connie Wu1, Aishwarya Sarma1

  • 1Berg, LLC, 500 Old Connecticut Path, Bldg B (3rd Floor), Framingham, MA 01701 USA.

Cell & Bioscience
|August 25, 2018
PubMed

Insights

CCDC47 is a novel calcium-regulating protein implicated in diabetic cardiomyopathy (DCM). This study identified CCDC47 in a DCM model and confirmed its role in calcium handling and early hypertrophic cardiomyopathy.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus, characterized by cardiac dysfunction not explained by other vascular diseases.
  • Calcium handling dysregulation is a known hallmark of cardiomyopathy, but specific alterations remain inconsistently defined.
  • Modeling DCM in human cardiomyocytes exposed to high glucose, fatty acids, and L-carnitine provides a platform to identify novel contributing proteins.

Purpose of the Study:

  • To identify novel calcium-regulating proteins involved in diabetic cardiomyopathy (DCM) using a proteomic approach.
  • To investigate the cellular and functional role of identified proteins in cardiac myocytes.
  • To assess the in vivo relevance of these proteins in a diet-induced obesity rat model of DCM.

Main Methods:

  • Proteomic analysis (iTRAQ-coupled LC-MS/MS) of human cardiomyocytes exposed to a high-nutrient perturbation mimicking DCM.
  • Comparison of identified proteins with the cardiovascular disease (CVD) gene ontology (GO) database to find novel CVD-associated proteins.
  • Functional assessment of CCDC47 in rat H9C2 myocytes and evaluation of its expression in a diet-induced obese (DIO) rat model of DCM.

Main Results:

  • CCDC47 (calumin) was identified as a novel calcium-regulating protein altered in the in vitro DCM model.
  • Overexpression of CCDC47 in rat myocytes increased ionomycin-induced calcium release and reuptake.
  • In DIO rats, CCDC47 mRNA increased in the atrium and ventricle, with significantly increased protein levels in the atrium.

Conclusions:

  • CCDC47 is a unique calcium-regulating protein associated with early-onset hypertrophic cardiomyopathy.
  • The findings highlight CCDC47 as a potential therapeutic target for DCM.
  • This study provides new insights into the molecular mechanisms underlying DCM and cardiac hypertrophy.
Abstract

Keywords:
CCDC47Calcium handlingDiabetic cardiomyopathy

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