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July 5, 2026Journal of the American Heart AssociationOpen Access

Cardiomyocyte‐Specific Smad7 Protects the Pressure‐Overloaded Heart, Inhibiting the Transforming Growth Factor‐β Receptor 1/Smad2/3 Cascade

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Key result

Cardiomyocyte Smad7 knockout in mice worsens systolic and diastolic dysfunction and hypertrophy after pressure overload.

Why the study?

The mechanisms underlying how cardiomyocyte Smad7 upregulation contributes to the pathogenesis of pressure overload-induced heart failure remained to be investigated.

Population

Mice undergoing transverse aortic constriction and cardiomyocyte-like H9c2 cells

Comparison

Cardiomyocyte-specific Smad7 knockout vs controls

Design

Preclinical animal and cell-culture experimental study

Authors

CHClaudio HumeresAlbert Einstein College of MedicineITIzabela TuletaHeart Failure & TransplantDQDongze QinNankai University

Discussion

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Implication

Smad7 may protect against overload-induced dysfunction; hypothesis-generating for targeted therapies but leaves open clinical translation.

Key Points

  • The aim is to investigate the role of cardiomyocyte-specific Smad7 in pressure overload-induced heart failure and its mechanisms.
  • Conducted transverse aortic constriction in controls to simulate pressure overload.
  • Performed echocardiographic, histological, transcriptomic, and proteomic analyses.
  • Assessed Smad7's effects on TGF-β and ERBB2 cascades using in vivo models and H9c2 cells.
  • Smad7 was upregulated in cardiomyocytes and fibroblasts after pressure overload and in nonischemic cardiomyopathy patients.
  • Smad7 knockout mice exhibited worsened heart function and increased hypertrophy under pressure overload conditions.
  • Bioinformatic analysis revealed TGF-β1 and ERBB2 as upstream regulators contributing to the effects of Smad7 loss.

Structured PICO

P
Population
Cardiomyocyte-specific Smad7 knockout mice and controls undergoing transverse aortic constriction; H9c2 cells; patients with nonischemic cardiomyopathy.
I
Intervention
Cardiomyocyte-specific Smad7 knockout
C
Comparator
Controls undergoing transverse aortic constriction
O
Outcome
Cardiac systolic and diastolic function, cardiomyocyte hypertrophy, and molecular signaling (TGFBR1/Smad2/3 and ERBB2 cascades)surrogate

Cardiomyocyte Smad7 protects the pressure-overloaded heart from dysfunction and hypertrophy by directly suppressing TGFBR1/Smad3 signaling.

Cite This Study

Humeres et al. (2026) studied Pressure overload-induced heart failure. Cardiomyocyte-specific Smad7 knockout vs. Controls was evaluated on Systolic and diastolic dysfunction and cardiomyocyte hypertrophy after pressure overload. Cardiomyocyte-specific Smad7 knockout mice developed worse systolic and diastolic dysfunction and increased cardiomyocyte hypertrophy after pressure overload.

synapsesocial.com/papers/6a49f464f5d1d45b287ffe27https://doi.org/10.1161/jaha.125.045203
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Endothelial deletion of protein tyrosine phosphatase-1B protects against pressure overload-induced heart failure in mice2016 · 58 citations
  2. 2Intercellular Adhesion Molecule 1 Regulates Left Ventricular Leukocyte Infiltration, Cardiac Remodeling, and Function in Pressure Overload–Induced Heart Failure2016 · 143 citations
  3. 3Cardiac-Specific Deletion of Gata4 Reveals Its Requirement for Hypertrophy, Compensation, and Myocyte Viability2006 · 430 citations
  4. 4The role of endogenous Smad7 in regulating macrophage phenotype following myocardial infarction2022 · 14 citations
  5. 5TGF-β as a therapeutic target in the infarcted and failing heart: cellular mechanisms, challenges, and opportunities2024 · 36 citations