Knockout of Trpa1 accelerates age-related cardiac fibrosis and dysfunction
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 aime...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9473441/?tool=EBI |
| _version_ | 1811267427160293376 |
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| author | Shuangtao Ma Donna H. Wang |
| author_facet | Shuangtao Ma Donna H. Wang |
| author_sort | Shuangtao Ma |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T21:02:21Z |
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| id | doaj.art-4d0118d123674b8d9a26df81a0f27cc7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T21:02:21Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4d0118d123674b8d9a26df81a0f27cc72022-12-22T03:16:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01179Knockout of Trpa1 accelerates age-related cardiac fibrosis and dysfunctionShuangtao MaDonna H. WangAge-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.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9473441/?tool=EBI |
| spellingShingle | Shuangtao Ma Donna H. Wang Knockout of Trpa1 accelerates age-related cardiac fibrosis and dysfunction PLoS ONE |
| title | Knockout of Trpa1 accelerates age-related cardiac fibrosis and dysfunction |
| title_full | Knockout of Trpa1 accelerates age-related cardiac fibrosis and dysfunction |
| title_fullStr | Knockout of Trpa1 accelerates age-related cardiac fibrosis and dysfunction |
| title_full_unstemmed | Knockout of Trpa1 accelerates age-related cardiac fibrosis and dysfunction |
| title_short | Knockout of Trpa1 accelerates age-related cardiac fibrosis and dysfunction |
| title_sort | knockout of trpa1 accelerates age related cardiac fibrosis and dysfunction |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9473441/?tool=EBI |
| work_keys_str_mv | AT shuangtaoma knockoutoftrpa1acceleratesagerelatedcardiacfibrosisanddysfunction AT donnahwang knockoutoftrpa1acceleratesagerelatedcardiacfibrosisanddysfunction |