What is the clinical evidence from this study?

Study design: Other. Population: Cardiac allograft chronic rejection. Intervention: AAV2-mediated PDGF-A, -B, -C, and -D gene transfer. Primary outcome: Cardiac allograft inflammation, fibrosis, and arteriosclerosis.

What question did this study set out to answer?

To investigate the specific roles of platelet-derived growth factor (PDGF) ligands A through D in graft inflammation, fibrosis, and chronic rejection of rat cardiac allografts.

February 13, 2009Arteriosclerosis Thrombosis and Vascular BiologyOpen Access

PDGF-A, -C, and -D but not PDGF-B Increase TGF-β1 and Chronic Rejection in Rat Cardiac Allografts

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Key result

Intracoronary AAV2-mediated gene transfer of PDGF-A, -C, and -D, but not PDGF-B, significantly upregulated profibrotic TGF-beta1 mRNA and accelerated cardiac fibrosis and arteriosclerosis in rats.

Why the study?

Does AAV2-mediated gene transfer of specific PDGF ligands increase TGF-beta1 and chronic rejection in rat cardiac allografts?

Population

Rat cardiac allografts

Design

Preclinical

Authors

RTRaimo TuuminenBen-Gurion University of the Negev ANAntti I. NykänenUniversity of Helsinki RKR. KrebsUniversity of Helsinki

Discussion

Member takes

Implication

Extends PDGF isoform selectivity data in rat allografts; hypothesis-generating for targeted inhibition in chronic rejection.

Key Points

To investigate the specific roles of platelet-derived growth factor (PDGF) ligands A through D in graft inflammation, fibrosis, and chronic rejection of rat cardiac allografts.
Assessed PDGF ligand and receptor mRNA and protein distribution in rat models of acute and chronic cardiac allograft rejection.
Administered individual PDGF ligands (PDGF-A, -B, -C, or -D) directly into donor coronary arteries using adeno-associated virus-2 (AAV2) gene delivery.
Gene delivery of PDGF-A, PDGF-C, and PDGF-D significantly increased profibrotic TGF-beta1 mRNA expression and accelerated cardiac fibrosis and arteriosclerosis.
Gene transfer of PDGF-A and PDGF-D substantially amplified graft inflammation, whereas PDGF-B transfer failed to aggravate chronic rejection features.

Structured PICO

Does AAV2-mediated gene transfer of specific PDGF ligands increase TGF-beta1 and chronic rejection in rat cardiac allografts?

Population

Rat cardiac allografts

Intervention

Intracoronary adeno-associated virus-2 (AAV2)-mediated PDGF-A, PDGF-B, PDGF-C, and PDGF-D gene transfer

Outcome

Cardiac allograft inflammation, fibrosis, arteriosclerosis, and TGF-beta1 mRNA expressionsurrogate

PDGF-A, -C, and -D, but not PDGF-B, mediate profibrotic and proarteriosclerotic effects in rat cardiac allografts via the TGF-beta1 pathway, suggesting targeted inhibition may prevent chronic rejection.

Cite This Study

Tuuminen et al. (2009) studied Cardiac allograft chronic rejection. AAV2-mediated PDGF-A, -B, -C, and -D gene transfer was evaluated on Cardiac allograft inflammation, fibrosis, and arteriosclerosis. Intracoronary AAV2-mediated gene transfer of PDGF-A, -C, and -D, but not PDGF-B, significantly upregulated profibrotic TGF-beta1 mRNA and accelerated cardiac fibrosis and arteriosclerosis in rats.

synapsesocial.com/papers/6a0e4de0bc348c84f2fd99b1 https://doi.org/10.1161/atvbaha.108.178558

Topics

Heart transplantation

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PDGF-A, -C, and -D but not PDGF-B Increase TGF-β1 and Chronic Rejection in Rat Cardiac Allografts

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

PDGF-A, -C, and -D but not PDGF-B Increase TGF-β1 and Chronic Rejection in Rat Cardiac Allografts

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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Topics

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