Evidence map›Paper›PMID 41203011›Full record

ArticleJournal of molecular and cellular cardiology2026

Slit2-robo signaling regulates angiogenesis and repair following myocardial infarction.

David Wong, Matthew Tran, Julie Martinez, Itzetl Avila, Adrian Arrieta, Kyle Kalindjian, Elle Rathbun, Thomas M Vondriska, Eric M Small, Pearl Quijada

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of molecular and cellular cardiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

David WongDepartment of Integrative Biology and Physiology, University of California, Los Angeles, United States; Molecular, Cellular, and Integrative Physiology Graduate Program, University of California, Los Angeles, United States.
Matthew TranDepartment of Integrative Biology and Physiology, University of California, Los Angeles, United States.
Julie MartinezDepartment of Integrative Biology and Physiology, University of California, Los Angeles, United States; Molecular, Cellular, and Integrative Physiology Graduate Program, University of California, Los Angeles, United States.
Itzetl AvilaMolecular, Cellular, and Integrative Physiology Graduate Program, University of California, Los Angeles, United States; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, United States.
Adrian ArrietaDepartment of Anesthesiology & Perioperative Medicine, David Geffen School of Medicine at the University of California, Los Angeles, United States.
Kyle KalindjianComputational & Systems Biology, University of California, Los Angeles, United States.
Elle RathbunDepartment of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, United States.
Thomas M VondriskaDepartment of Anesthesiology & Perioperative Medicine, David Geffen School of Medicine at the University of California, Los Angeles, United States; Molecular Biology Institute, University of California, Los Angeles, United States.
Eric M SmallAab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, United States.
Pearl QuijadaDepartment of Integrative Biology and Physiology, University of California, Los Angeles, United States; Eli and Edythe Broad Stem Cell Research Center, University of California, Los Angeles, United States; Molecular Biology Institute, University of California, Los Angeles, United States. Electronic address: pquijada@ucla.edu.

Funding

Dynamics of Cardiac Nuclei in Heart DiseaseR01HL105699 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI VONDRISKA, THOMAS M. · 2011 to 2025
$5.0M
Regulation of angiogenesis by cardiac fibroblastsR01HL172852 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Pearl Jennine Quijada · 2025 to 2026
$1.5M
NHLBI NIH HHS R01 HL105699NHLBI NIH HHS R01 HL172852
6 · The paper itself

Abstract

The Slit2 guidance ligand and its Roundabout (Robo) family of receptors regulate axonal guidance and vascular patterning during cardiac morphogenesis, yet the role of Slit2-Robo signaling in the adult heart remains unclear. Here, we identified epicardium-derived Slit2 as highly enriched in neonatal cardiac fibroblasts (cFBs) but markedly reduced in adult hearts. Following myocardial infarction (MI), Slit2 transiently increases in the infarct border zone seven days post-MI but declines significantly after one month. In vitro, Slit2 overexpression in cFBs selectively upregulated angiogenic genes during myofibroblast differentiation without affecting extracellular matrix (ECM) gene expression. In vivo, AAV9-mediated cardiac-specific overexpression of Slit2 (AAV9-cTNT-Slit2) improved cardiac function, increased endothelial cell (EC) proliferation and vascular density, but did not alter fibrotic deposition following MI. Conditioned media from Slit2-overexpressing cFBs promoted EC proliferation, activation, and tube forming abilities, consistent with the increased expression of pro-angiogenic Robo1 and other vascular growth factors in the myocardium of AAV9-Slit2-treated hearts. Additionally, Slit2 overexpression attenuated cardiomyocyte hypertrophy after MI and suppressed fetal gene expression in vitro. Mechanistically, Slit2 appears to mediate its cardioprotective effects through enhanced interactions with Robo1 in cFBs and ECs. These findings support Slit2-Robo signaling as a promising therapeutic target for improving blood vessel formation and maintaining cardiac muscle integrity following ischemic injury.

Indexed as

Intercellular Signaling Peptides and ProteinsMyocardial InfarctionNeovascularization, PhysiologicNerve Tissue ProteinsReceptors, ImmunologicSignal TransductionAngiogenesisAnimalsCell DifferentiationCell ProliferationDisease Models, AnimalEndothelial CellsFibroblastsHumansMaleMiceIntercellular Signaling Peptides and ProteinsNerve Tissue ProteinsReceptors, ImmunologicRoundabout ProteinsSlit Homolog 2 ProteinAAV9 gene deliveryAngiogenesisCardiac fibroblastsCardiac repairEndothelial cellsHypertrophyMyocardial infarctionRobo1Robo4Slit2Vascular biologyVascular remodeling

Identifiers

PMID41203011
PMCPMC13218272

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.