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July 28, 2006Circulation ResearchOpen Access

Identification of Cell Cycle Regulatory and Inflammatory Genes As Predominant Targets of p38 Mitogen-Activated Protein Kinase in the Heart

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Key result

Cardiac-specific overexpression of p38 MAPK in rats upregulated 264 genes more than 2-fold, leading to myocardial cell proliferation, inflammation, and fibrosis.

Population

Rats (in vivo model)

Design

Preclinical

Authors

OTOlli TenhunenJRJaana RysäMIMika Ilves

Discussion

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Overview

Suggests p38 MAPK drives rodent myocardial fibrosis; leaves open its therapeutic targeting in human heart disease.

Structured PICO

P
Population
Rats (in vivo model)
I
Intervention
Local adenovirus-mediated gene transfer of constitutively active upstream kinase mitogen-activated protein kinase kinase 3b (MKK3bE) and wild-type p38alpha
O
Outcome
Cardiac gene-expression profile, transcription factor activation, histological changes, and echocardiographic measurementssurrogate

In vivo overexpression of p38 MAPK in the rat heart identifies its role in upregulating cell cycle and inflammatory genes, driving pathological myocardial proliferation and fibrosis.

Cite This Study

Tenhunen et al. (2006) studied this question. Adenovirus-mediated gene transfer of MKK3bE and wild-type p38alpha was evaluated on Gene expression profile and functional effects. Cardiac-specific overexpression of p38 MAPK in rats upregulated 264 genes more than 2-fold, leading to myocardial cell proliferation, inflammation, and fibrosis.

synapsesocial.com/papers/6a93319463ff76fc055fa7f4https://doi.org/10.1161/01.res.0000238387.85144.92
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Cardiac Muscle Cell Hypertrophy and Apoptosis Induced by Distinct Members of the p38 Mitogen-activated Protein Kinase Family1998 · 854 citations
  2. 2p38 MAP Kinase Mediates Inflammatory Cytokine Induction in Cardiomyocytes and Extracellular Matrix Remodeling in Heart2005 · 158 citations
  3. 3The <i>in vivo</i> role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy2001 · 339 citations
  4. 4Distinct gene expression profiles in adult mouse heart following targeted MAP kinase activation2005 · 46 citations
  5. 5Hypertensive End-Organ Damage and Premature Mortality Are p38 Mitogen-Activated Protein Kinase–Dependent in a Rat Model of Cardiac Hypertrophy and Dysfunction2001 · 118 citations