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June 22, 2023Circulation ResearchOpen Access

PDCD5 reduces post-MI cardiac fibrosis and dysfunction by promoting HDAC3 ubiquitination and inhibition.

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Why the study?

Progressive cardiac fibrosis leads to ventricular wall stiffness, dysfunction, and heart failure, but the role and underlying mechanisms of PDCD5 in cardiac fibrosis remain largely unknown.

Does PDCD5 overexpression reduce cardiac fibrosis and improve cardiac function post-myocardial infarction?

Population

Patients with cardiac fibrosis, post-myocardial infarction mice, and stimulated cardiac fibroblasts

Comparison

PDCD5 overexpression, protein treatment, or knock-in vs knockdown, control, or HDAC3 overexpression

Design

Preclinical laboratory and animal study

Key result

PDCD5, upregulated by SMAD3, ameliorated progressive cardiac fibrosis and cardiac dysfunction post-myocardial infarction by promoting HDAC3 ubiquitination and inhibition.

Authors

LWLin WengJYJingjing YeFYFenghe Yang

Discussion

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Member takes

Overview

May support PDCD5 modulation to limit post-MI fibrosis; hypothesis-generating in animal models and requires clinical validation.

Structured PICO

Does PDCD5 overexpression reduce cardiac fibrosis and improve cardiac function post-myocardial infarction?

P
Population
Serum from patients with cardiac fibrosis, fibrotic mice heart tissues post-myocardial infarction, and cardiac fibroblasts stimulated by Ang II or TGF-β1
I
Intervention
PDCD5 overexpression or treatment with PDCD5 protein; fibroblast-specific knock-in of PDCD5 in mice
C
Comparator
Control conditions; PDCD5 knockdown; AAV9-mediated HDAC3 overexpression
O
Outcome
Cardiac fibrosis and cardiac functionsurrogate

PDCD5 acts as a negative feedback factor on fibrotic signaling pathways and may be a potential therapeutic target to suppress cardiac fibrosis post-myocardial infarction.

Cite This Study

Weng et al. (2023) studied Cardiac fibrosis post-myocardial infarction. PDCD5 overexpression or knock-in vs. Control, PDCD5 knockdown, or HDAC3 overexpression was evaluated on Cardiac fibrosis and cardiac function. PDCD5, upregulated by SMAD3, ameliorated progressive cardiac fibrosis and cardiac dysfunction post-myocardial infarction by promoting HDAC3 ubiquitination and inhibition.

synapsesocial.com/papers/6a0f1ab6a7a2fed64abdb6fahttps://doi.org/10.1161/circresaha.123.322596
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