miR-133a-3p/TRPM4 axis improves palmitic acid induced vascular endothelial injury
Background: Vascular endothelial injury is a contributing factor to the development of atherosclerosis and the resulting cardiovascular diseases. One particular factor involved in endothelial cell apoptosis and atherosclerosis is palmitic acid (PA), which is a long-chain saturated fatty acid. In add...
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| Format: | Article |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1340247/full |
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| author | Yadong Xue Tingting Tong Yuyao Zhang Haijun Huang Ling Zhao Hongzhao Lv Lingzhao Xiong Kai Zhang Yuxuan Han Yuyang Fu Yongzhen Wang Rong Huo Ning Wang Tao Ban Tao Ban Tao Ban Tao Ban |
| author_facet | Yadong Xue Tingting Tong Yuyao Zhang Haijun Huang Ling Zhao Hongzhao Lv Lingzhao Xiong Kai Zhang Yuxuan Han Yuyang Fu Yongzhen Wang Rong Huo Ning Wang Tao Ban Tao Ban Tao Ban Tao Ban |
| author_sort | Yadong Xue |
| collection | DOAJ |
| description | Background: Vascular endothelial injury is a contributing factor to the development of atherosclerosis and the resulting cardiovascular diseases. One particular factor involved in endothelial cell apoptosis and atherosclerosis is palmitic acid (PA), which is a long-chain saturated fatty acid. In addition, transient receptor potential melastatin 4 (TRPM4), a non-selective cation channel, plays a significant role in endothelial dysfunction caused by various factors related to cardiovascular diseases. Despite this, the specific role and mechanisms of TRPM4 in atherosclerosis have not been fully understood.Methods: The protein and mRNA expressions of TRPM4, apoptosis - and inflammation-related factors were measured after PA treatment. The effect of TRPM4 knockout on the protein and mRNA expression of apoptosis and inflammation-related factors was detected. The changes of intracellular Ca2+, mitochondrial membrane potential, and reactive oxygen species were detected by Fluo-4 AM, JC-1, and DCFH-DA probes, respectively. To confirm the binding of miR-133a-3p to TRPM4, a dual luciferase reporter gene assay was conducted. Finally, the effects of miR-133a-3p and TRPM4 on intracellular Ca2+, mitochondrial membrane potential, and reactive oxygen species were examined.Results: Following PA treatment, the expression of TRPM4 increases, leading to calcium overload in endothelial cells. This calcium influx causes the assemblage of Bcl-2, resulting in the opening of mitochondrial calcium channels and mitochondrial damage, ultimately triggering apoptosis. Throughout this process, the mRNA and protein levels of IL-1β, ICAM-1, and VCAM1 significantly increase. Database screenings and luciferase assays have shown that miR-133a-3p preferentially binds to the 3′UTR region of TRPM4 mRNA, suppressing TRPM4 expression. During PA-induced endothelial injury, miR-133a-3p is significantly decreased, but overexpression of miR-133a-3p can attenuate the progression of endothelial injury. On the other hand, overexpression of TRPM4 counteracts the aforementioned changes.Conclusion: TRPM4 participates in vascular endothelial injury caused by PA. Therefore, targeting TRPM4 or miR-133a-3p may offer a novel pharmacological approach to preventing endothelial injury. |
| first_indexed | 2024-03-08T14:46:28Z |
| format | Article |
| id | doaj.art-eae598952d024f3c844bc1b2add31e2f |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-08T14:46:28Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-eae598952d024f3c844bc1b2add31e2f2024-01-11T09:50:36ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-01-011410.3389/fphar.2023.13402471340247miR-133a-3p/TRPM4 axis improves palmitic acid induced vascular endothelial injuryYadong Xue0Tingting Tong1Yuyao Zhang2Haijun Huang3Ling Zhao4Hongzhao Lv5Lingzhao Xiong6Kai Zhang7Yuxuan Han8Yuyang Fu9Yongzhen Wang10Rong Huo11Ning Wang12Tao Ban13Tao Ban14Tao Ban15Tao Ban16Department of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education, State Key Laboratory of Frigid Zone Cardiovascular Diseases, Ministry of Science and Technology) at College of Pharmacy, Harbin Medical University, Harbin, ChinaDepartment of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education, State Key Laboratory of Frigid Zone Cardiovascular Diseases, Ministry of Science and Technology) at College of Pharmacy, Harbin Medical University, Harbin, ChinaDepartment of Anatomy, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, ChinaDepartment of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education, State Key Laboratory of Frigid Zone Cardiovascular Diseases, Ministry of Science and Technology) at College of Pharmacy, Harbin Medical University, Harbin, ChinaDepartment of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education, State Key Laboratory of Frigid Zone Cardiovascular Diseases, Ministry of Science and Technology) at College of Pharmacy, Harbin Medical University, Harbin, ChinaDepartment of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education, State Key Laboratory of Frigid Zone Cardiovascular Diseases, Ministry of Science and Technology) at College of Pharmacy, Harbin Medical University, Harbin, ChinaDepartment of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education, State Key Laboratory of Frigid Zone Cardiovascular Diseases, Ministry of Science and Technology) at College of Pharmacy, Harbin Medical University, Harbin, ChinaDepartment of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education, State Key Laboratory of Frigid Zone Cardiovascular Diseases, Ministry of Science and Technology) at College of Pharmacy, Harbin Medical University, Harbin, ChinaDepartment of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education, State Key Laboratory of Frigid Zone Cardiovascular Diseases, Ministry of Science and Technology) at College of Pharmacy, Harbin Medical University, Harbin, ChinaDepartment of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education, State Key Laboratory of Frigid Zone Cardiovascular Diseases, Ministry of Science and Technology) at College of Pharmacy, Harbin Medical University, Harbin, ChinaDepartment of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education, State Key Laboratory of Frigid Zone Cardiovascular Diseases, Ministry of Science and Technology) at College of Pharmacy, Harbin Medical University, Harbin, ChinaDepartment of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education, State Key Laboratory of Frigid Zone Cardiovascular Diseases, Ministry of Science and Technology) at College of Pharmacy, Harbin Medical University, Harbin, ChinaDepartment of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education, State Key Laboratory of Frigid Zone Cardiovascular Diseases, Ministry of Science and Technology) at College of Pharmacy, Harbin Medical University, Harbin, ChinaDepartment of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education, State Key Laboratory of Frigid Zone Cardiovascular Diseases, Ministry of Science and Technology) at College of Pharmacy, Harbin Medical University, Harbin, ChinaDepartment of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaHeilongjiang Academy of Medical Sciences, Harbin, ChinaNational-Local Joint Engineering Laboratory of Drug Research and Development of Cardio-Cerebrovascular Diseases in Frigid Zone, The National Development and Reform Commission, Harbin, ChinaBackground: Vascular endothelial injury is a contributing factor to the development of atherosclerosis and the resulting cardiovascular diseases. One particular factor involved in endothelial cell apoptosis and atherosclerosis is palmitic acid (PA), which is a long-chain saturated fatty acid. In addition, transient receptor potential melastatin 4 (TRPM4), a non-selective cation channel, plays a significant role in endothelial dysfunction caused by various factors related to cardiovascular diseases. Despite this, the specific role and mechanisms of TRPM4 in atherosclerosis have not been fully understood.Methods: The protein and mRNA expressions of TRPM4, apoptosis - and inflammation-related factors were measured after PA treatment. The effect of TRPM4 knockout on the protein and mRNA expression of apoptosis and inflammation-related factors was detected. The changes of intracellular Ca2+, mitochondrial membrane potential, and reactive oxygen species were detected by Fluo-4 AM, JC-1, and DCFH-DA probes, respectively. To confirm the binding of miR-133a-3p to TRPM4, a dual luciferase reporter gene assay was conducted. Finally, the effects of miR-133a-3p and TRPM4 on intracellular Ca2+, mitochondrial membrane potential, and reactive oxygen species were examined.Results: Following PA treatment, the expression of TRPM4 increases, leading to calcium overload in endothelial cells. This calcium influx causes the assemblage of Bcl-2, resulting in the opening of mitochondrial calcium channels and mitochondrial damage, ultimately triggering apoptosis. Throughout this process, the mRNA and protein levels of IL-1β, ICAM-1, and VCAM1 significantly increase. Database screenings and luciferase assays have shown that miR-133a-3p preferentially binds to the 3′UTR region of TRPM4 mRNA, suppressing TRPM4 expression. During PA-induced endothelial injury, miR-133a-3p is significantly decreased, but overexpression of miR-133a-3p can attenuate the progression of endothelial injury. On the other hand, overexpression of TRPM4 counteracts the aforementioned changes.Conclusion: TRPM4 participates in vascular endothelial injury caused by PA. Therefore, targeting TRPM4 or miR-133a-3p may offer a novel pharmacological approach to preventing endothelial injury.https://www.frontiersin.org/articles/10.3389/fphar.2023.1340247/fullvascular endothelial injuryhyperlipidemiapalmitic acidTRPM4MiR-133a-3p |
| spellingShingle | Yadong Xue Tingting Tong Yuyao Zhang Haijun Huang Ling Zhao Hongzhao Lv Lingzhao Xiong Kai Zhang Yuxuan Han Yuyang Fu Yongzhen Wang Rong Huo Ning Wang Tao Ban Tao Ban Tao Ban Tao Ban miR-133a-3p/TRPM4 axis improves palmitic acid induced vascular endothelial injury Frontiers in Pharmacology vascular endothelial injury hyperlipidemia palmitic acid TRPM4 MiR-133a-3p |
| title | miR-133a-3p/TRPM4 axis improves palmitic acid induced vascular endothelial injury |
| title_full | miR-133a-3p/TRPM4 axis improves palmitic acid induced vascular endothelial injury |
| title_fullStr | miR-133a-3p/TRPM4 axis improves palmitic acid induced vascular endothelial injury |
| title_full_unstemmed | miR-133a-3p/TRPM4 axis improves palmitic acid induced vascular endothelial injury |
| title_short | miR-133a-3p/TRPM4 axis improves palmitic acid induced vascular endothelial injury |
| title_sort | mir 133a 3p trpm4 axis improves palmitic acid induced vascular endothelial injury |
| topic | vascular endothelial injury hyperlipidemia palmitic acid TRPM4 MiR-133a-3p |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1340247/full |
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