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Updated: May 12, 2026

Generation and Expansion of Human Cardiomyocytes from Patient Peripheral Blood Mononuclear Cells
05:38

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Published on: February 12, 2021

Cardiomyocytes HIPK2 regulates myocardial inflammation and heart function through purinergic signaling

Sultan Tousif1,2, Arvind Singh Bhati3, Allen Sam Titus3

  • 1Division of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, USA. tousif.sultan@lsuhs.edu.

Cell Communication and Signaling : CCS
|May 11, 2026
PubMed

Insights

Homeodomain-interacting protein kinase 2 (HIPK2) regulates purinergic signaling critical for heart function. Loss of HIPK2 causes inflammation and cardiac dysfunction, highlighting its importance in maintaining heart health.

Area of Science:

  • Cardiovascular Biology
  • Molecular Mechanisms of Disease
  • Cell Signaling

Background:

  • Purinergic signaling plays a vital role in myocardial inflammation and function.
  • The precise molecular mechanisms regulating purinergic signaling in the heart remain incompletely understood.

Purpose of the Study:

  • To identify novel regulators of purinergic signaling in the heart.
  • To elucidate the role of homeodomain-interacting protein kinase 2 (HIPK2) in cardiac purinergic signaling and inflammation.

Main Methods:

  • Generated cardiomyocyte-specific HIPK2 knockout (CM-HIPK2-KO) mice.
  • Utilized in vitro gain-of-function (Ad-HIPK2) and loss-of-function (Ad-sh-RNA-HIPK2) models.
  • Investigated the HIPK2-ERK-CREB signaling pathway and its transcriptional control on CD39 and CD73.
  • Assessed cardiac function and inflammation markers in response to HIPK2 manipulation and pharmacological interventions.

Main Results:

  • CM-HIPK2-KO hearts showed reduced expression of CD39 and CD73, leading to excessive inflammation and cardiac dysfunction.
  • HIPK2 regulates purinergic signaling via the HIPK2-ERK-CREB pathway, controlling CD39 and CD73 transcription.
  • Inhibition of purinergic signaling (apyrase) or NLRP3 inflammasome (CY09) ameliorated cardiac pathology in CM-HIPK2-KO models.

Conclusions:

  • HIPK2 is identified as a novel and critical regulator of purinergic signaling in the heart.
  • HIPK2 deficiency results in dysregulated purinergic signaling, promoting inflammation and cardiac dysfunction.
  • Maintaining HIPK2 levels is crucial for preserving cardiac health and preventing pathological inflammation.

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