April 29, 2025Open Access

LOSS OF ROR2 TYROSINE KINASE RECEPTOR IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION IN PAH VIA INAPPROPRIATE INTEGRIN β1 ACTIVATION

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Why the study?

The role of ROR2, a Wnt/PCP-specific tyrosine kinase receptor crucial for cardiovascular development, in pulmonary arterial hypertension and pulmonary endothelial homeostasis was unclear.

Population

Endothelial-specific ROR2 knockout and wild-type mice, and PMVECs from healthy and PAH lungs

Comparison

ROR2 ECKO vs wild-type under normoxia and chronic hypoxia, and PMVECs transfected with ROR2 siRNA/constructs

Design

Preclinical animal and cellular experimental study

Authors

AMAnkita MitraCardiovascular Institute of the South ACAnanya ChakrabortyAnna Needs Neuroblastoma Answers BZBrian L. ZhongPalo Alto University

Discussion

Member takes

Implication

ROR2 may be a therapeutic target in PAH; leaves open translation from murine hypoxia models to human disease.

Structured PICO

Population

Endothelial-specific ROR2 knockout (ROR2 ECKO) and wild-type (WT) mice (C57BL/6J background); human pulmonary microvascular endothelial cells (PMVECs) from healthy donors and PAH lungs.

Intervention

Endothelial-specific ROR2 knockout (in vivo); ROR2 knockdown via siRNA or ROR2 restoration via construct (in vitro).

Comparator

Wild-type mice (in vivo); non-targeting siRNA or vector alone (in vitro).

Outcome

Pulmonary hypertension severity (RVSP), right ventricular remodeling, microvascular loss, muscularization, and endothelial barrier integrity.surrogate

ROR2 regulates pulmonary angiogenesis by maintaining endothelial barrier integrity, and its loss exacerbates pulmonary hypertension, highlighting ROR2 restoration as a potential therapeutic approach for PAH.

Cite This Study

Mitra et al. (2025) studied this question.

synapsesocial.com/papers/6a821b95a221e60789ca348a https://doi.org/10.1101/2025.04.28.651135

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LOSS OF ROR2 TYROSINE KINASE RECEPTOR IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION IN PAH VIA INAPPROPRIATE INTEGRIN β1 ACTIVATION

Discussion

Member takes

Implication

Structured PICO

Cite This Study

LOSS OF ROR2 TYROSINE KINASE RECEPTOR IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION IN PAH VIA INAPPROPRIATE INTEGRIN β1 ACTIVATION

Discussion

Member takes

Implication

Structured PICO

Cite This Study

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