What is the clinical evidence from this study?

Study design: Other. Population: Right ventricular failure. Intervention: ROR2 overexpression or knockdown. Primary outcome: Tissue compaction and stretch-induced stiffness (p=<0.01).

What type of study is this?

This is a Experimental Study study.

October 9, 2025Circulation Research

Abstract Thu147: The Complex Role of ROR2 in Fibroblast Activation and Tissue Mechanics

Q: What are the key findings of this study?

ROR2 knockdown in engineered human fibroblast tissues increased compaction and stretch-induced stiffness (1.59 vs 1.146 mN/mm2, p<0.01), with disparate effects observed between rat and human cells.

Q: What type of study is this?

This is a Experimental Study study.

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Key result

ROR2 knockdown increases human cardiac tissue stiffness ~39% under stretch, highlighting species-specific remodeling differences.

P<0.01

Why the study?

Does ROR2 modulation affect fibroblast activation and tissue mechanics in neonatal rat and adult human ventricular fibroblasts?

Population

Primary ventricular fibroblasts from neonatal rats (NRVFs) and adult human heart (HuFBs) cell line

Design

Preclinical

Authors

HHHali HartmanChildren's Hospital of Philadelphia HRHari RajagopalCohen Children's Medical Center VSVictor SenfUniversity of Pennsylvania

Discussion

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Implication

ROR2 has significant and opposing effects on neonatal rat and adult human ventricular fibroblasts, impacting migration, proliferation, and tissue mechanics in the context of right ventricular failure.

Key Points

ROR2 enhances wound healing in neonatal rat ventricular fibroblasts while decreasing proliferation in human fibroblasts.
CellProfiler analysis demonstrated that ROR2 impact on cell migration is linked to weakened cell junctions in both NRVFs and HuFBs.
ROR2 knockdown resulted in increased tissue stiffness and compaction, indicating its critical role in cardiac fibroblast function.
Study suggests that ROR2 may have age and species-dependent effects that could influence therapeutic strategies for right ventricular failure.

Structured PICO

Does ROR2 modulation affect fibroblast activation and tissue mechanics in neonatal rat and adult human ventricular fibroblasts?

Population

Primary ventricular fibroblasts from neonatal rats (NRVFs) and adult human heart (HuFBs) cell line

Intervention

Adenovirus-mediated overexpression (ROR2 OE) or knockdown (ROR2 KD) of ROR2

Outcome

Wound healing, injury provoked proliferation, cell junctions, tissue compaction, and stretch induced stiffnesssurrogate

Main Result

Absolute Event Rate: 1.59% vs 1.146%

p-value: p=<0.01

Limitations

Future clinical translatability to RVF will require further work to unravel the disparate ROR2 effects on NRVFs and HuFBs (e.g. age vs species).
Disparate ROR2 effects on NRVFs and HuFBs (e.g. age vs species) requiring further work for clinical translatability

Cite This Study

Hartman et al. (2025) studied Right ventricular failure. ROR2 overexpression or knockdown was evaluated on Tissue compaction and stretch-induced stiffness (p=<0.01). ROR2 knockdown in engineered human fibroblast tissues increased compaction and stretch-induced stiffness (1.59 vs 1.146 mN/mm2, p<0.01), with disparate effects observed between rat and human cells.

synapsesocial.com/papers/68e77f09d1c187e1c108fb43 https://doi.org/10.1161/res.137.suppl_1.thu147

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Abstract Thu147: The Complex Role of ROR2 in Fibroblast Activation and Tissue Mechanics

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Limitations

Cite This Study

Abstract Thu147: The Complex Role of ROR2 in Fibroblast Activation and Tissue Mechanics

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Also Consider