Circulating exosomal mir-16-2-3p is associated with coronary microvascular dysfunction in diabetes through regulating the fatty acid degradation of endothelial cells
Abstract Background Coronary microvascular dysfunction (CMD) is a frequent complication of diabetes mellitus (DM) characterized by challenges in both diagnosis and intervention. Circulating levels of microRNAs are increasingly recognized as potential biomarkers for cardiovascular diseases. Methods S...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-02-01
|
| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-024-02142-0 |
| _version_ | 1797275967698239488 |
|---|---|
| author | Yihai Liu Chongxia Zhong Shan Chen Yanan Xue Zhonghai Wei Li Dong Lina Kang |
| author_facet | Yihai Liu Chongxia Zhong Shan Chen Yanan Xue Zhonghai Wei Li Dong Lina Kang |
| author_sort | Yihai Liu |
| collection | DOAJ |
| description | Abstract Background Coronary microvascular dysfunction (CMD) is a frequent complication of diabetes mellitus (DM) characterized by challenges in both diagnosis and intervention. Circulating levels of microRNAs are increasingly recognized as potential biomarkers for cardiovascular diseases. Methods Serum exosomes from patients with DM, DM with coronary microvascular dysfunction (DM-CMD) or DM with coronary artery disease (DM-CAD) were extracted for miRNA sequencing. The expression of miR-16-2-3p was assessed in high glucose-treated human aortic endothelial cells and human cardiac microvascular endothelial cells. Fluorescence in situ hybridization (FISH) was used to detect miR-16-2-3p within the myocardium of db/db mice. Intramyocardial injection of lentivirus overexpressing miR-16-2-3p was used to explore the function of the resulting gene in vivo. Bioinformatic analysis and in vitro assays were carried out to explore the downstream function and mechanism of miR-16-2-3p. Wound healing and tube formation assays were used to explore the effect of miR-16-2-3p on endothelial cell function. Results miR-16-2-3p was upregulated in circulating exosomes from DM-CMD, high glucose-treated human cardiac microvascular endothelial cells and the hearts of db/db mice. Cardiac miR-16-2-3p overexpression improved cardiac systolic and diastolic function and coronary microvascular reperfusion. In vitro experiments revealed that miR-16-2-3p could regulate fatty acid degradation in endothelial cells, and ACADM was identified as a potential downstream target. MiR-16-2-3p increased cell migration and tube formation in microvascular endothelial cells. Conclusions Our findings suggest that circulating miR-16-2-3p may serve as a biomarker for individuals with DM-CMD. Additionally, miR-16-2-3p appears to alleviate coronary microvascular dysfunction in diabetes by modulating ACADM-mediated fatty acid degradation in endothelial cells. |
| first_indexed | 2024-03-07T15:21:38Z |
| format | Article |
| id | doaj.art-24bcd3fde08940d8a8fbd561b613fbca |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-03-07T15:21:38Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-24bcd3fde08940d8a8fbd561b613fbca2024-03-05T17:36:32ZengBMCCardiovascular Diabetology1475-28402024-02-0123111510.1186/s12933-024-02142-0Circulating exosomal mir-16-2-3p is associated with coronary microvascular dysfunction in diabetes through regulating the fatty acid degradation of endothelial cellsYihai Liu0Chongxia Zhong1Shan Chen2Yanan Xue3Zhonghai Wei4Li Dong5Lina Kang6Department of Cardiology, Affiliated Drum Tower Hospital of Nanjing University Medical SchoolDepartment of Cardiology, Affiliated Drum Tower Hospital of Nanjing University Medical SchoolDepartment of General Medicine, Affiliated Drum Tower Hospital of Nanjing University Medical SchoolDepartment of Cardiology, Affiliated Drum Tower Hospital of Nanjing University Medical SchoolDepartment of Cardiology, Affiliated Drum Tower Hospital of Nanjing University Medical SchoolDepartment of Geriatrics, Nanjing Central HospitalDepartment of Cardiology, Affiliated Drum Tower Hospital of Nanjing University Medical SchoolAbstract Background Coronary microvascular dysfunction (CMD) is a frequent complication of diabetes mellitus (DM) characterized by challenges in both diagnosis and intervention. Circulating levels of microRNAs are increasingly recognized as potential biomarkers for cardiovascular diseases. Methods Serum exosomes from patients with DM, DM with coronary microvascular dysfunction (DM-CMD) or DM with coronary artery disease (DM-CAD) were extracted for miRNA sequencing. The expression of miR-16-2-3p was assessed in high glucose-treated human aortic endothelial cells and human cardiac microvascular endothelial cells. Fluorescence in situ hybridization (FISH) was used to detect miR-16-2-3p within the myocardium of db/db mice. Intramyocardial injection of lentivirus overexpressing miR-16-2-3p was used to explore the function of the resulting gene in vivo. Bioinformatic analysis and in vitro assays were carried out to explore the downstream function and mechanism of miR-16-2-3p. Wound healing and tube formation assays were used to explore the effect of miR-16-2-3p on endothelial cell function. Results miR-16-2-3p was upregulated in circulating exosomes from DM-CMD, high glucose-treated human cardiac microvascular endothelial cells and the hearts of db/db mice. Cardiac miR-16-2-3p overexpression improved cardiac systolic and diastolic function and coronary microvascular reperfusion. In vitro experiments revealed that miR-16-2-3p could regulate fatty acid degradation in endothelial cells, and ACADM was identified as a potential downstream target. MiR-16-2-3p increased cell migration and tube formation in microvascular endothelial cells. Conclusions Our findings suggest that circulating miR-16-2-3p may serve as a biomarker for individuals with DM-CMD. Additionally, miR-16-2-3p appears to alleviate coronary microvascular dysfunction in diabetes by modulating ACADM-mediated fatty acid degradation in endothelial cells.https://doi.org/10.1186/s12933-024-02142-0miR-16-2-3pDiabetesCoronary microvascular dysfunctionExosomesMicrovascular endothelial cells |
| spellingShingle | Yihai Liu Chongxia Zhong Shan Chen Yanan Xue Zhonghai Wei Li Dong Lina Kang Circulating exosomal mir-16-2-3p is associated with coronary microvascular dysfunction in diabetes through regulating the fatty acid degradation of endothelial cells Cardiovascular Diabetology miR-16-2-3p Diabetes Coronary microvascular dysfunction Exosomes Microvascular endothelial cells |
| title | Circulating exosomal mir-16-2-3p is associated with coronary microvascular dysfunction in diabetes through regulating the fatty acid degradation of endothelial cells |
| title_full | Circulating exosomal mir-16-2-3p is associated with coronary microvascular dysfunction in diabetes through regulating the fatty acid degradation of endothelial cells |
| title_fullStr | Circulating exosomal mir-16-2-3p is associated with coronary microvascular dysfunction in diabetes through regulating the fatty acid degradation of endothelial cells |
| title_full_unstemmed | Circulating exosomal mir-16-2-3p is associated with coronary microvascular dysfunction in diabetes through regulating the fatty acid degradation of endothelial cells |
| title_short | Circulating exosomal mir-16-2-3p is associated with coronary microvascular dysfunction in diabetes through regulating the fatty acid degradation of endothelial cells |
| title_sort | circulating exosomal mir 16 2 3p is associated with coronary microvascular dysfunction in diabetes through regulating the fatty acid degradation of endothelial cells |
| topic | miR-16-2-3p Diabetes Coronary microvascular dysfunction Exosomes Microvascular endothelial cells |
| url | https://doi.org/10.1186/s12933-024-02142-0 |
| work_keys_str_mv | AT yihailiu circulatingexosomalmir1623pisassociatedwithcoronarymicrovasculardysfunctionindiabetesthroughregulatingthefattyaciddegradationofendothelialcells AT chongxiazhong circulatingexosomalmir1623pisassociatedwithcoronarymicrovasculardysfunctionindiabetesthroughregulatingthefattyaciddegradationofendothelialcells AT shanchen circulatingexosomalmir1623pisassociatedwithcoronarymicrovasculardysfunctionindiabetesthroughregulatingthefattyaciddegradationofendothelialcells AT yananxue circulatingexosomalmir1623pisassociatedwithcoronarymicrovasculardysfunctionindiabetesthroughregulatingthefattyaciddegradationofendothelialcells AT zhonghaiwei circulatingexosomalmir1623pisassociatedwithcoronarymicrovasculardysfunctionindiabetesthroughregulatingthefattyaciddegradationofendothelialcells AT lidong circulatingexosomalmir1623pisassociatedwithcoronarymicrovasculardysfunctionindiabetesthroughregulatingthefattyaciddegradationofendothelialcells AT linakang circulatingexosomalmir1623pisassociatedwithcoronarymicrovasculardysfunctionindiabetesthroughregulatingthefattyaciddegradationofendothelialcells |