Signaling via the Interleukin-10 Receptor Attenuates Cardiac Hypertrophy in Mice During Pressure Overload, but not Isoproterenol Infusion
Inflammation plays a key role during cardiac hypertrophy and the development of heart failure. Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that is expressed in the heart and may play a crucial role in cardiac remodeling. Based on the evidence that IL-10 potentially reduces pathologi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.559220/full |
| _version_ | 1819277459700318208 |
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| author | Nicholas Stafford Nicholas Stafford Farryah Assrafally Farryah Assrafally Sukhpal Prehar Sukhpal Prehar Min Zi Min Zi Ana M. De Morais Ana M. De Morais Arfa Maqsood Arfa Maqsood Elizabeth J. Cartwright Elizabeth J. Cartwright Werner Mueller Delvac Oceandy Delvac Oceandy |
| author_facet | Nicholas Stafford Nicholas Stafford Farryah Assrafally Farryah Assrafally Sukhpal Prehar Sukhpal Prehar Min Zi Min Zi Ana M. De Morais Ana M. De Morais Arfa Maqsood Arfa Maqsood Elizabeth J. Cartwright Elizabeth J. Cartwright Werner Mueller Delvac Oceandy Delvac Oceandy |
| author_sort | Nicholas Stafford |
| collection | DOAJ |
| description | Inflammation plays a key role during cardiac hypertrophy and the development of heart failure. Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that is expressed in the heart and may play a crucial role in cardiac remodeling. Based on the evidence that IL-10 potentially reduces pathological hypertrophy, it was hypothesized that signaling via the IL-10 receptor (IL10R) in the heart produces a protective role in reducing cardiac hypertrophy. The aim of this study was to investigate the effects of the ablation of Il-10-r1 gene during pathological cardiac hypertrophy in mice. We found that IL-10R1 gene silencing in cultured cardiomyocytes diminished the anti-hypertrophic effect of Il-10 in TNF-α induced hypertrophy model. We then analyzed mice deficient in the Il-10-r1 gene (IL-10R1-/- mice) and subjected them to transverse aortic constriction or isoproterenol infusion to induce pathological hypertrophy. In response to transverse aortic constriction for 2 weeks, IL-10R1-/- mice displayed a significant increase in the hypertrophic response as indicated by heart weight/body weight ratio, which was accompanied by significant increases in cardiomyocyte surface area and interstitial fibrosis. In contrast, there was no difference in hypertrophic response to isoproterenol infusion (10 days) between the knockout and control groups. Analysis of cardiac function using echocardiography and invasive hemodynamic studies did not show any difference between the WT and IL-10R1-/- groups, most likely due to the short term nature of the models. In conclusion, our data shows that signaling via the IL-10 receptor may produce protective effects against pressure overload-induced hypertrophy but not against β-adrenergic stimuli in the heart. Our data supports previous evidence that signaling modulated by IL-10 and its receptor may become a potential target to control pathological cardiac hypertrophy. |
| first_indexed | 2024-12-23T23:56:27Z |
| format | Article |
| id | doaj.art-e5f06703bb704b3e80ecfeaefb2e1497 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-23T23:56:27Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e5f06703bb704b3e80ecfeaefb2e14972022-12-21T17:25:15ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-10-011110.3389/fphar.2020.559220559220Signaling via the Interleukin-10 Receptor Attenuates Cardiac Hypertrophy in Mice During Pressure Overload, but not Isoproterenol InfusionNicholas Stafford0Nicholas Stafford1Farryah Assrafally2Farryah Assrafally3Sukhpal Prehar4Sukhpal Prehar5Min Zi6Min Zi7Ana M. De Morais8Ana M. De Morais9Arfa Maqsood10Arfa Maqsood11Elizabeth J. Cartwright12Elizabeth J. Cartwright13Werner Mueller14Delvac Oceandy15Delvac Oceandy16Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United KingdomManchester Academic Health Science Centre, The University of Manchester, Manchester, United KingdomDivision of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United KingdomManchester Academic Health Science Centre, The University of Manchester, Manchester, United KingdomDivision of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United KingdomManchester Academic Health Science Centre, The University of Manchester, Manchester, United KingdomDivision of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United KingdomManchester Academic Health Science Centre, The University of Manchester, Manchester, United KingdomDivision of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United KingdomManchester Academic Health Science Centre, The University of Manchester, Manchester, United KingdomDivision of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United KingdomManchester Academic Health Science Centre, The University of Manchester, Manchester, United KingdomDivision of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United KingdomManchester Academic Health Science Centre, The University of Manchester, Manchester, United KingdomSchool of Biological Sciences, The University of Manchester, Manchester, United KingdomDivision of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United KingdomManchester Academic Health Science Centre, The University of Manchester, Manchester, United KingdomInflammation plays a key role during cardiac hypertrophy and the development of heart failure. Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that is expressed in the heart and may play a crucial role in cardiac remodeling. Based on the evidence that IL-10 potentially reduces pathological hypertrophy, it was hypothesized that signaling via the IL-10 receptor (IL10R) in the heart produces a protective role in reducing cardiac hypertrophy. The aim of this study was to investigate the effects of the ablation of Il-10-r1 gene during pathological cardiac hypertrophy in mice. We found that IL-10R1 gene silencing in cultured cardiomyocytes diminished the anti-hypertrophic effect of Il-10 in TNF-α induced hypertrophy model. We then analyzed mice deficient in the Il-10-r1 gene (IL-10R1-/- mice) and subjected them to transverse aortic constriction or isoproterenol infusion to induce pathological hypertrophy. In response to transverse aortic constriction for 2 weeks, IL-10R1-/- mice displayed a significant increase in the hypertrophic response as indicated by heart weight/body weight ratio, which was accompanied by significant increases in cardiomyocyte surface area and interstitial fibrosis. In contrast, there was no difference in hypertrophic response to isoproterenol infusion (10 days) between the knockout and control groups. Analysis of cardiac function using echocardiography and invasive hemodynamic studies did not show any difference between the WT and IL-10R1-/- groups, most likely due to the short term nature of the models. In conclusion, our data shows that signaling via the IL-10 receptor may produce protective effects against pressure overload-induced hypertrophy but not against β-adrenergic stimuli in the heart. Our data supports previous evidence that signaling modulated by IL-10 and its receptor may become a potential target to control pathological cardiac hypertrophy.https://www.frontiersin.org/articles/10.3389/fphar.2020.559220/fullinterleukin-10cardiac hypertrophysignaling pathwayinflammationheart failure |
| spellingShingle | Nicholas Stafford Nicholas Stafford Farryah Assrafally Farryah Assrafally Sukhpal Prehar Sukhpal Prehar Min Zi Min Zi Ana M. De Morais Ana M. De Morais Arfa Maqsood Arfa Maqsood Elizabeth J. Cartwright Elizabeth J. Cartwright Werner Mueller Delvac Oceandy Delvac Oceandy Signaling via the Interleukin-10 Receptor Attenuates Cardiac Hypertrophy in Mice During Pressure Overload, but not Isoproterenol Infusion Frontiers in Pharmacology interleukin-10 cardiac hypertrophy signaling pathway inflammation heart failure |
| title | Signaling via the Interleukin-10 Receptor Attenuates Cardiac Hypertrophy in Mice During Pressure Overload, but not Isoproterenol Infusion |
| title_full | Signaling via the Interleukin-10 Receptor Attenuates Cardiac Hypertrophy in Mice During Pressure Overload, but not Isoproterenol Infusion |
| title_fullStr | Signaling via the Interleukin-10 Receptor Attenuates Cardiac Hypertrophy in Mice During Pressure Overload, but not Isoproterenol Infusion |
| title_full_unstemmed | Signaling via the Interleukin-10 Receptor Attenuates Cardiac Hypertrophy in Mice During Pressure Overload, but not Isoproterenol Infusion |
| title_short | Signaling via the Interleukin-10 Receptor Attenuates Cardiac Hypertrophy in Mice During Pressure Overload, but not Isoproterenol Infusion |
| title_sort | signaling via the interleukin 10 receptor attenuates cardiac hypertrophy in mice during pressure overload but not isoproterenol infusion |
| topic | interleukin-10 cardiac hypertrophy signaling pathway inflammation heart failure |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2020.559220/full |
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