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Positive feedback loop of miR-320 and CD36 regulates the hyperglycemic memory-induced diabetic diastolic cardiac dysfunction
Intensive glycemic control is insufficient for reducing the risk of heart failure among patients with diabetes mellitus (DM). While the “hyperglycemic memory” phenomenon is well documented, little is known about its underlying mechanisms. In this study, a type 1 DM model was established in C57BL/6 m...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9813582/ https://www.ncbi.nlm.nih.gov/pubmed/36618264 http://dx.doi.org/10.1016/j.omtn.2022.12.009 |
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author | Zhan, Jiabing Jin, Kunying Ding, Nan Zhou, Yufei Hu, Guo Yuan, Shuai Xie, Rong Wen, Zheng Chen, Chen Li, Huaping Wang, Dao Wen |
author_facet | Zhan, Jiabing Jin, Kunying Ding, Nan Zhou, Yufei Hu, Guo Yuan, Shuai Xie, Rong Wen, Zheng Chen, Chen Li, Huaping Wang, Dao Wen |
author_sort | Zhan, Jiabing |
collection | PubMed |
description | Intensive glycemic control is insufficient for reducing the risk of heart failure among patients with diabetes mellitus (DM). While the “hyperglycemic memory” phenomenon is well documented, little is known about its underlying mechanisms. In this study, a type 1 DM model was established in C57BL/6 mice using streptozotocin (STZ). Leptin receptor-deficient (db/db) mice were used as a model of type 2 DM. A type 9 adeno-associated virus was used to overexpress or knock down miR-320 in vivo. Diastolic dysfunction was observed in the type 1 DM mice with elevated miR-320 expression. However, glycemic control using insulin failed to reverse diastolic dysfunction. miR-320 knockdown protected against STZ-induced diastolic dysfunction. Similar results were observed in the type 2 DM mice. In vitro, we found that miR-320 promoted CD36 expression, which in turn induced further miR-320 expression. CD36 was rapidly induced by hyperglycemia at protein level compared with the much slower induction of miR-320, suggesting a positive feedback loop of CD36/miR-320 with CD36 protein induction as the initial triggering event. In conclusion, in DM-induced cardiac injury, miR-320 and CD36 mutually enhance each other’s expression, leading to a positive feedback loop and a sustained hyperlipidemic state in the heart. |
format | Online Article Text |
id | pubmed-9813582 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-98135822023-01-05 Positive feedback loop of miR-320 and CD36 regulates the hyperglycemic memory-induced diabetic diastolic cardiac dysfunction Zhan, Jiabing Jin, Kunying Ding, Nan Zhou, Yufei Hu, Guo Yuan, Shuai Xie, Rong Wen, Zheng Chen, Chen Li, Huaping Wang, Dao Wen Mol Ther Nucleic Acids Original Article Intensive glycemic control is insufficient for reducing the risk of heart failure among patients with diabetes mellitus (DM). While the “hyperglycemic memory” phenomenon is well documented, little is known about its underlying mechanisms. In this study, a type 1 DM model was established in C57BL/6 mice using streptozotocin (STZ). Leptin receptor-deficient (db/db) mice were used as a model of type 2 DM. A type 9 adeno-associated virus was used to overexpress or knock down miR-320 in vivo. Diastolic dysfunction was observed in the type 1 DM mice with elevated miR-320 expression. However, glycemic control using insulin failed to reverse diastolic dysfunction. miR-320 knockdown protected against STZ-induced diastolic dysfunction. Similar results were observed in the type 2 DM mice. In vitro, we found that miR-320 promoted CD36 expression, which in turn induced further miR-320 expression. CD36 was rapidly induced by hyperglycemia at protein level compared with the much slower induction of miR-320, suggesting a positive feedback loop of CD36/miR-320 with CD36 protein induction as the initial triggering event. In conclusion, in DM-induced cardiac injury, miR-320 and CD36 mutually enhance each other’s expression, leading to a positive feedback loop and a sustained hyperlipidemic state in the heart. American Society of Gene & Cell Therapy 2022-12-14 /pmc/articles/PMC9813582/ /pubmed/36618264 http://dx.doi.org/10.1016/j.omtn.2022.12.009 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Zhan, Jiabing Jin, Kunying Ding, Nan Zhou, Yufei Hu, Guo Yuan, Shuai Xie, Rong Wen, Zheng Chen, Chen Li, Huaping Wang, Dao Wen Positive feedback loop of miR-320 and CD36 regulates the hyperglycemic memory-induced diabetic diastolic cardiac dysfunction |
title | Positive feedback loop of miR-320 and CD36 regulates the hyperglycemic memory-induced diabetic diastolic cardiac dysfunction |
title_full | Positive feedback loop of miR-320 and CD36 regulates the hyperglycemic memory-induced diabetic diastolic cardiac dysfunction |
title_fullStr | Positive feedback loop of miR-320 and CD36 regulates the hyperglycemic memory-induced diabetic diastolic cardiac dysfunction |
title_full_unstemmed | Positive feedback loop of miR-320 and CD36 regulates the hyperglycemic memory-induced diabetic diastolic cardiac dysfunction |
title_short | Positive feedback loop of miR-320 and CD36 regulates the hyperglycemic memory-induced diabetic diastolic cardiac dysfunction |
title_sort | positive feedback loop of mir-320 and cd36 regulates the hyperglycemic memory-induced diabetic diastolic cardiac dysfunction |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9813582/ https://www.ncbi.nlm.nih.gov/pubmed/36618264 http://dx.doi.org/10.1016/j.omtn.2022.12.009 |
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