Monoamine Oxidase-Dependent Pro-Survival Signaling in Diabetic Hearts Is Mediated by miRNAs
Diabetes leads to cardiomyopathy and heart failure, the leading cause of death for diabetic patients. Monoamine oxidase (MAO) inhibition in diabetic cardiomyopathy prevents oxidative stress, mitochondrial and endoplasmic reticulum stress and the development of diastolic dysfunction. However, it is u...
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MDPI AG
2022-08-01
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| author | Stefano Cagnin Marco Brugnaro Caterina Millino Beniamina Pacchioni Carmen Troiano Moises Di Sante Nina Kaludercic |
| author_facet | Stefano Cagnin Marco Brugnaro Caterina Millino Beniamina Pacchioni Carmen Troiano Moises Di Sante Nina Kaludercic |
| author_sort | Stefano Cagnin |
| collection | DOAJ |
| description | Diabetes leads to cardiomyopathy and heart failure, the leading cause of death for diabetic patients. Monoamine oxidase (MAO) inhibition in diabetic cardiomyopathy prevents oxidative stress, mitochondrial and endoplasmic reticulum stress and the development of diastolic dysfunction. However, it is unclear whether, in addition to the direct effects exerted on the mitochondria, MAO activity is able to post-transcriptionally regulate cardiomyocyte function and survival in diabetes. To this aim, we performed gene and miRNA expression profiling in cardiac tissue from streptozotocin-treated mice (model of type 1 diabetes (T1D)), administered with either vehicle or MAOs inhibitor pargyline for 12 weeks. We found that inhibition of MAO activity in T1D hearts leads to profound transcriptomic changes, affecting autophagy and pro-survival pathways activation. MAO activity in T1D hearts increased miR-133a-3p, -193a-3p and -27a-3p expression. These miRNAs target insulin-like growth factor receptor 1 (<i>Igf1r</i>), growth factor receptor bound protein 10 and inositol polyphosphate 4 phosphatase type 1A, respectively, all components of the IGF1R/PI3K/AKT signaling pathway. Indeed, AKT activation was significantly downregulated in T1D hearts, whereas MAO inhibition restored the activation of this pro-survival pathway. The present study provides an important link between MAO activity, transcriptomic changes and activation of pro-survival signaling and autophagy in diabetic cardiomyopathy. |
| first_indexed | 2024-03-10T01:57:27Z |
| format | Article |
| id | doaj.art-fafd3d261cd2432d8cf47da1b4b61068 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:57:27Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-fafd3d261cd2432d8cf47da1b4b610682023-11-23T12:55:30ZengMDPI AGCells2073-44092022-08-011117269710.3390/cells11172697Monoamine Oxidase-Dependent Pro-Survival Signaling in Diabetic Hearts Is Mediated by miRNAsStefano Cagnin0Marco Brugnaro1Caterina Millino2Beniamina Pacchioni3Carmen Troiano4Moises Di Sante5Nina Kaludercic6Department of Biology, University of Padova, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova, 35131 Padova, ItalyDepartment of Biology, University of Padova, 35131 Padova, ItalyDepartment of Biology, University of Padova, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova, 35131 Padova, ItalyDiabetes leads to cardiomyopathy and heart failure, the leading cause of death for diabetic patients. Monoamine oxidase (MAO) inhibition in diabetic cardiomyopathy prevents oxidative stress, mitochondrial and endoplasmic reticulum stress and the development of diastolic dysfunction. However, it is unclear whether, in addition to the direct effects exerted on the mitochondria, MAO activity is able to post-transcriptionally regulate cardiomyocyte function and survival in diabetes. To this aim, we performed gene and miRNA expression profiling in cardiac tissue from streptozotocin-treated mice (model of type 1 diabetes (T1D)), administered with either vehicle or MAOs inhibitor pargyline for 12 weeks. We found that inhibition of MAO activity in T1D hearts leads to profound transcriptomic changes, affecting autophagy and pro-survival pathways activation. MAO activity in T1D hearts increased miR-133a-3p, -193a-3p and -27a-3p expression. These miRNAs target insulin-like growth factor receptor 1 (<i>Igf1r</i>), growth factor receptor bound protein 10 and inositol polyphosphate 4 phosphatase type 1A, respectively, all components of the IGF1R/PI3K/AKT signaling pathway. Indeed, AKT activation was significantly downregulated in T1D hearts, whereas MAO inhibition restored the activation of this pro-survival pathway. The present study provides an important link between MAO activity, transcriptomic changes and activation of pro-survival signaling and autophagy in diabetic cardiomyopathy.https://www.mdpi.com/2073-4409/11/17/2697diabetic cardiomyopathyautophagymonoamine oxidasemiRNAspro-survival pathways |
| spellingShingle | Stefano Cagnin Marco Brugnaro Caterina Millino Beniamina Pacchioni Carmen Troiano Moises Di Sante Nina Kaludercic Monoamine Oxidase-Dependent Pro-Survival Signaling in Diabetic Hearts Is Mediated by miRNAs Cells diabetic cardiomyopathy autophagy monoamine oxidase miRNAs pro-survival pathways |
| title | Monoamine Oxidase-Dependent Pro-Survival Signaling in Diabetic Hearts Is Mediated by miRNAs |
| title_full | Monoamine Oxidase-Dependent Pro-Survival Signaling in Diabetic Hearts Is Mediated by miRNAs |
| title_fullStr | Monoamine Oxidase-Dependent Pro-Survival Signaling in Diabetic Hearts Is Mediated by miRNAs |
| title_full_unstemmed | Monoamine Oxidase-Dependent Pro-Survival Signaling in Diabetic Hearts Is Mediated by miRNAs |
| title_short | Monoamine Oxidase-Dependent Pro-Survival Signaling in Diabetic Hearts Is Mediated by miRNAs |
| title_sort | monoamine oxidase dependent pro survival signaling in diabetic hearts is mediated by mirnas |
| topic | diabetic cardiomyopathy autophagy monoamine oxidase miRNAs pro-survival pathways |
| url | https://www.mdpi.com/2073-4409/11/17/2697 |
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