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March 14, 2023Frontiers in Cardiovascular MedicineOpen Access

Depletion of Yap/Wwtr1 in myofibroblasts resulted in smaller scars, reduced interstitial fibrosis, and improved ejection fraction and fractional shortening, while CCN3 administration aggravated cardiac function and scarring.

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Why the study?

While Yap and Wwtr1 regulate resident cardiac fibroblast to myofibroblast differentiation after cardiac injury, their role specifically in activated myofibroblasts remains unexplored.

Population

Adult mice following myocardial infarction

Comparison

Depletion of Yap alone vs Yap and Wwtr1 in myofibroblasts, and recombinant CCN3 administration

Design

Preclinical animal and in vitro mechanistic study

Authors

MFMichael A. FlinnSASantiago Alvarez‐ArgoteMKMakenna Knas

Discussion

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Overview

Myofibroblast Yap/Wwtr1 depletion findings are hypothesis-generating; leaves open therapeutic translation to human post-MI fibrosis.

Structured PICO

P
Population
Adult (6-10 weeks old) and P6 neonatal mice, and Sprague Dawley neonatal rats subjected to myocardial infarction via left anterior descending (LAD) coronary artery ligation.
I
Intervention
Genetic depletion of Yap alone (Yapfl/fl;PostnMCM) or Yap and Wwtr1 (Yapfl/fl;Wwtr1fl/+;PostnMCM) in myofibroblasts via tamoxifen induction; and in vivo administration of recombinant CCN3 (6 µg/kg intraperitoneal injection 3 times weekly for 28 days).
C
Comparator
Cre negative controls receiving identical tamoxifen dosing; vehicle control animals receiving PBS via intraperitoneal injection.
O
Outcome
Cardiac function (ejection fraction, fractional shortening) and scarring/interstitial fibrosis post-myocardial infarction.surrogate

Yap/Wwtr1 depletion in myofibroblasts attenuates fibrosis and improves cardiac outcomes after myocardial infarction, identifying Ccn3 as a downstream driver of adverse remodeling.

Cite This Study

Flinn et al. (2023) studied this question.

synapsesocial.com/papers/6a7227a3ac440176ef2a88d3https://doi.org/10.3389/fcvm.2023.1142612
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Also Consider

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

  1. 1Myofibroblast Ccn3 is regulated by Yap and Wwtr1 and contributes to adverse cardiac outcomes2022 · 1 citations
  2. 2Abstract Thu138: Myofibroblast CCN3 Contributes to Adverse Outcomes Following Myocardial Infarction2025
  3. 3AAV-mediated YAP expression in cardiac fibroblasts promotes inflammation and increases fibrosis2021 · 60 citations
  4. 4Cardiac fibroblast anisotropy is determined by YAP-dependent cellular contractility and ECM production2026
  5. 5Yes-Associated Protein is Involved in Myocardial Fibrosis in Rats with Diabetic Cardiomyopathy2021 · 10 citations