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Tytuł:
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Knockout of Trpa1 accelerates age-related cardiac fibrosis and dysfunction.
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Autorzy:
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Ma S; Division of Nanomedicine and Molecular Intervention, Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Michigan, United States of America.
Wang DH; Division of Nanomedicine and Molecular Intervention, Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Michigan, United States of America.
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Źródło:
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PloS one [PLoS One] 2022 Sep 14; Vol. 17 (9), pp. e0274618. Date of Electronic Publication: 2022 Sep 14 (Print Publication: 2022).
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: San Francisco, CA : Public Library of Science
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MeSH Terms:
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Heart Failure*
Ventricular Function, Left*/physiology
Animals ; Cardiomegaly ; Fibrosis ; Mice ; Mice, Knockout ; Stroke Volume/genetics ; TRPA1 Cation Channel/genetics
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References:
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Substance Nomenclature:
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0 (TRPA1 Cation Channel)
0 (Trpa1 protein, mouse)
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Entry Date(s):
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Date Created: 20220914 Date Completed: 20220916 Latest Revision: 20220930
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Update Code:
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20240105
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PubMed Central ID:
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PMC9473441
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DOI:
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10.1371/journal.pone.0274618
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PMID:
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36103570
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Age-related cardiac fibrosis contributes to the development of heart failure with preserved ejection fraction which lacks ideal treatment. Transient receptor potential ankyrin 1 (TRPA1) is an oxidative stress sensor and could attenuate age-related pathologies in invertebrates. The present study aimed to test whether TRPA1 plays a role in age-related cardiac remodeling and dysfunction. The cardiac function and pathology of 12-week-old (young) and 52-week-old (older) Trpa1-/- mice and wild-type (WT) littermates were evaluated by echocardiography and histologic analyses. The expression levels of 84 fibrosis-related genes in the heart were measured by quantitative polymerase chain reaction array. Young Trpa1-/- and WT mice had similar left ventricular wall thickness, volume, and systolic and diastolic function. Older Trpa1-/- mice had significantly increased left ventricular internal diameter and volume and impaired systolic (lower left ventricular ejection fraction) and diastolic (higher E/A ratio and isovolumetric relaxation time) functions compared with older WT mice (P<0.05 or P<0.01). Importantly, older Trpa1-/- mice had enhanced cardiac fibrosis than older WT mice (P<0.05) while the two strains had similar degree of cardiac hypertrophy. Among the 84 fibrosis-related genes, Acta2, Inhbe, Ifng, and Ccl11 were significantly upregulated, while Timp3, Stat6, and Ilk were significantly downregulated in the heart of older Trpa1-/- mice compared with older WT mice. Taken together, we found that knocking out Trpa1 accelerated age-related myocardial fibrosis, ventricular dilation, and cardiac dysfunction. These findings suggest that TRPA1 may become a therapeutic target for preventing and/or treating cardiac fibrosis and heart failure with preserved ejection fraction in the elderly.
Competing Interests: The authors have declared that no competing interests exist.
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