Homocysteine Promotes the Pathogenesis of Atherosclerosis through the Circ‐PIAS1‐5/miR‐219a‐2‐3p/TEAD1 Axis
Abstract Previous studies have established a possible link between hyperhomocysteinemia (HHcy) and dyslipidemia. Circular RNAs (circRNAs) play important regulatory roles in the development of atherosclerosis. However, the biological functions and potential molecular mechanisms of circRNAs in HHcy‐in...
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202415563 |
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| author | Shengchao Ma Fei Ma Ning Ding Lin Xie Anning Yang Jiangyong Shen Yun jiao Kai Wu YueE Chai Zhigang Bai Jiantuan Xiong Nan Li Huiping Zhang Yideng Jiang |
| author_facet | Shengchao Ma Fei Ma Ning Ding Lin Xie Anning Yang Jiangyong Shen Yun jiao Kai Wu YueE Chai Zhigang Bai Jiantuan Xiong Nan Li Huiping Zhang Yideng Jiang |
| author_sort | Shengchao Ma |
| collection | DOAJ |
| description | Abstract Previous studies have established a possible link between hyperhomocysteinemia (HHcy) and dyslipidemia. Circular RNAs (circRNAs) play important regulatory roles in the development of atherosclerosis. However, the biological functions and potential molecular mechanisms of circRNAs in HHcy‐induced lipid accumulation leading to atherosclerosis are still unclear. In this study, it is determined that homocysteine (Hcy) downregulates the expression of circ‐PIAS1‐5 by global circRNA expression profiling and that circ‐PIAS1‐5 inhibits Hcy‐mediated lipid accumulation in foam cells and the pathogenesis of atherosclerosis by acting as a sponge for miR‐219a‐2‐3p. Circ‐PIAS1‐5 is identified as a potential diagnostic biomarker of HHcy‐associated atherosclerosis in male “apolipoprotein E knockout (ApoE−/−)” mice. Mechanistically, circ‐PIAS1‐5 activates the adenosine 5‘‐monophosphate (AMP)‐activated protein kinase pathway by regulating TEAD1 through miR‐219a‐2‐3p, and Hcy mediates the m6A modification and nuclear export of circ‐PIAS1‐5 via YTHDC1 to increase lipid accumulation in foam cells and accelerate the pathogenesis of atherosclerosis. Taken together, these results highlight the role of circ‐PIAS1‐5 in the Hcy‐mediated pathogenesis of atherosclerosis and suggest its potential application as a prognostic biomarker of atherosclerosis induced by HHcy. |
| format | Article |
| id | doaj-art-301676eab1ae4baf9943983f9b046bde |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-301676eab1ae4baf9943983f9b046bde2025-08-20T03:11:14ZengWileyAdvanced Science2198-38442025-05-011218n/an/a10.1002/advs.202415563Homocysteine Promotes the Pathogenesis of Atherosclerosis through the Circ‐PIAS1‐5/miR‐219a‐2‐3p/TEAD1 AxisShengchao Ma0Fei Ma1Ning Ding2Lin Xie3Anning Yang4Jiangyong Shen5Yun jiao6Kai Wu7YueE Chai8Zhigang Bai9Jiantuan Xiong10Nan Li11Huiping Zhang12Yideng Jiang13NHC Key Laboratory of Metabolic Cardiovascular Diseases Research Ningxia Medical University Yinchuan 750004 ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research Ningxia Medical University Yinchuan 750004 ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research Ningxia Medical University Yinchuan 750004 ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research Ningxia Medical University Yinchuan 750004 ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research Ningxia Medical University Yinchuan 750004 ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research Ningxia Medical University Yinchuan 750004 ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research Ningxia Medical University Yinchuan 750004 ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research Ningxia Medical University Yinchuan 750004 ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research Ningxia Medical University Yinchuan 750004 ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research Ningxia Medical University Yinchuan 750004 ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research Ningxia Medical University Yinchuan 750004 ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research Ningxia Medical University Yinchuan 750004 ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research Ningxia Medical University Yinchuan 750004 ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research Ningxia Medical University Yinchuan 750004 ChinaAbstract Previous studies have established a possible link between hyperhomocysteinemia (HHcy) and dyslipidemia. Circular RNAs (circRNAs) play important regulatory roles in the development of atherosclerosis. However, the biological functions and potential molecular mechanisms of circRNAs in HHcy‐induced lipid accumulation leading to atherosclerosis are still unclear. In this study, it is determined that homocysteine (Hcy) downregulates the expression of circ‐PIAS1‐5 by global circRNA expression profiling and that circ‐PIAS1‐5 inhibits Hcy‐mediated lipid accumulation in foam cells and the pathogenesis of atherosclerosis by acting as a sponge for miR‐219a‐2‐3p. Circ‐PIAS1‐5 is identified as a potential diagnostic biomarker of HHcy‐associated atherosclerosis in male “apolipoprotein E knockout (ApoE−/−)” mice. Mechanistically, circ‐PIAS1‐5 activates the adenosine 5‘‐monophosphate (AMP)‐activated protein kinase pathway by regulating TEAD1 through miR‐219a‐2‐3p, and Hcy mediates the m6A modification and nuclear export of circ‐PIAS1‐5 via YTHDC1 to increase lipid accumulation in foam cells and accelerate the pathogenesis of atherosclerosis. Taken together, these results highlight the role of circ‐PIAS1‐5 in the Hcy‐mediated pathogenesis of atherosclerosis and suggest its potential application as a prognostic biomarker of atherosclerosis induced by HHcy.https://doi.org/10.1002/advs.202415563atherosclerosiscirc‐PIAS1‐5homocysteinemiR‐219a‐2‐3pYTHDC1 |
| spellingShingle | Shengchao Ma Fei Ma Ning Ding Lin Xie Anning Yang Jiangyong Shen Yun jiao Kai Wu YueE Chai Zhigang Bai Jiantuan Xiong Nan Li Huiping Zhang Yideng Jiang Homocysteine Promotes the Pathogenesis of Atherosclerosis through the Circ‐PIAS1‐5/miR‐219a‐2‐3p/TEAD1 Axis Advanced Science atherosclerosis circ‐PIAS1‐5 homocysteine miR‐219a‐2‐3p YTHDC1 |
| title | Homocysteine Promotes the Pathogenesis of Atherosclerosis through the Circ‐PIAS1‐5/miR‐219a‐2‐3p/TEAD1 Axis |
| title_full | Homocysteine Promotes the Pathogenesis of Atherosclerosis through the Circ‐PIAS1‐5/miR‐219a‐2‐3p/TEAD1 Axis |
| title_fullStr | Homocysteine Promotes the Pathogenesis of Atherosclerosis through the Circ‐PIAS1‐5/miR‐219a‐2‐3p/TEAD1 Axis |
| title_full_unstemmed | Homocysteine Promotes the Pathogenesis of Atherosclerosis through the Circ‐PIAS1‐5/miR‐219a‐2‐3p/TEAD1 Axis |
| title_short | Homocysteine Promotes the Pathogenesis of Atherosclerosis through the Circ‐PIAS1‐5/miR‐219a‐2‐3p/TEAD1 Axis |
| title_sort | homocysteine promotes the pathogenesis of atherosclerosis through the circ pias1 5 mir 219a 2 3p tead1 axis |
| topic | atherosclerosis circ‐PIAS1‐5 homocysteine miR‐219a‐2‐3p YTHDC1 |
| url | https://doi.org/10.1002/advs.202415563 |
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