Novel Insights into the Cardioprotective Effects of Calcitriol in Myocardial Infarction
Background: Increasing evidence indicates that vitamin D deficiency negatively affects the cardiovascular system. Here we studied the therapeutic effects of calcitriol in myocardial infarction (MI) and investigated its underlying mechanisms. Methods: A MI model of Kun-ming mice induced by left anter...
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2022-05-01
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| author | Simin Yang Chunmiao Wang Chengshao Ruan Meiling Chen Ran Cao Liang Sheng Naiying Chang Tong Xu Peiwen Zhao Xuesheng Liu Fengqin Zhu Qingzhong Xiao Shan Gao |
| author_facet | Simin Yang Chunmiao Wang Chengshao Ruan Meiling Chen Ran Cao Liang Sheng Naiying Chang Tong Xu Peiwen Zhao Xuesheng Liu Fengqin Zhu Qingzhong Xiao Shan Gao |
| author_sort | Simin Yang |
| collection | DOAJ |
| description | Background: Increasing evidence indicates that vitamin D deficiency negatively affects the cardiovascular system. Here we studied the therapeutic effects of calcitriol in myocardial infarction (MI) and investigated its underlying mechanisms. Methods: A MI model of Kun-ming mice induced by left anterior descending coronary artery ligation was utilized to study the potential therapeutic effects of calcitriol on MI. AC16 human cardiomyocyte-like cells treated with TNF-α were used for exploring the mechanisms that underlie the cardioprotective effects of calcitriol. Results: We observed that calcitriol reversed adverse cardiovascular function and cardiac remodeling in post-MI mice. Mechanistically, calcitriol suppressed MI-induced cardiac inflammation, ameliorated cardiomyocyte death, and promoted cardiomyocyte proliferation. Specifically, calcitriol exerted these cellular effects by upregulating Vitamin D receptor (VDR). Increased VDR directly interacted with p65 and retained p65 in cytoplasm, thereby dampening NF-κB signaling and suppressing inflammation. Moreover, up-regulated VDR was translocated into nuclei where it directly bound to <i>IL-10</i> gene promoters to activate <i>IL-10</i> gene transcription, further inhibiting inflammation. Conclusion: We provide new insights into the cellular and molecular mechanisms underlying the cardioprotective effects of calcitriol, and we present comprehensive evidence to support the preventive and therapeutic effects of calcitriol on MI. |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T03:09:20Z |
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| series | Cells |
| spelling | doaj.art-172a187d6d7b4e378cb9f290273abf222023-11-23T10:28:04ZengMDPI AGCells2073-44092022-05-011110167610.3390/cells11101676Novel Insights into the Cardioprotective Effects of Calcitriol in Myocardial InfarctionSimin Yang0Chunmiao Wang1Chengshao Ruan2Meiling Chen3Ran Cao4Liang Sheng5Naiying Chang6Tong Xu7Peiwen Zhao8Xuesheng Liu9Fengqin Zhu10Qingzhong Xiao11Shan Gao12Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, ChinaDepartment of Cardiology, The First Affiliated Hospital, Anhui Medical University, Hefei 230022, ChinaDepartment of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, ChinaDepartment of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, ChinaDepartment of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, ChinaDepartment of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, ChinaDepartment of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, ChinaDepartment of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, ChinaDepartment of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, ChinaDepartment of Anesthesiology, The First Affiliated Hospital, Anhui Medical University, Hefei 230022, ChinaCancer Hospital, Chinese Academy of Sciences, Hefei 230031, ChinaClinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UKDepartment of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, ChinaBackground: Increasing evidence indicates that vitamin D deficiency negatively affects the cardiovascular system. Here we studied the therapeutic effects of calcitriol in myocardial infarction (MI) and investigated its underlying mechanisms. Methods: A MI model of Kun-ming mice induced by left anterior descending coronary artery ligation was utilized to study the potential therapeutic effects of calcitriol on MI. AC16 human cardiomyocyte-like cells treated with TNF-α were used for exploring the mechanisms that underlie the cardioprotective effects of calcitriol. Results: We observed that calcitriol reversed adverse cardiovascular function and cardiac remodeling in post-MI mice. Mechanistically, calcitriol suppressed MI-induced cardiac inflammation, ameliorated cardiomyocyte death, and promoted cardiomyocyte proliferation. Specifically, calcitriol exerted these cellular effects by upregulating Vitamin D receptor (VDR). Increased VDR directly interacted with p65 and retained p65 in cytoplasm, thereby dampening NF-κB signaling and suppressing inflammation. Moreover, up-regulated VDR was translocated into nuclei where it directly bound to <i>IL-10</i> gene promoters to activate <i>IL-10</i> gene transcription, further inhibiting inflammation. Conclusion: We provide new insights into the cellular and molecular mechanisms underlying the cardioprotective effects of calcitriol, and we present comprehensive evidence to support the preventive and therapeutic effects of calcitriol on MI.https://www.mdpi.com/2073-4409/11/10/1676calcitriolvitamin Dmyocardial infarctioncardiovascular diseasecardiac inflammation and remodelingNF-κB |
| spellingShingle | Simin Yang Chunmiao Wang Chengshao Ruan Meiling Chen Ran Cao Liang Sheng Naiying Chang Tong Xu Peiwen Zhao Xuesheng Liu Fengqin Zhu Qingzhong Xiao Shan Gao Novel Insights into the Cardioprotective Effects of Calcitriol in Myocardial Infarction Cells calcitriol vitamin D myocardial infarction cardiovascular disease cardiac inflammation and remodeling NF-κB |
| title | Novel Insights into the Cardioprotective Effects of Calcitriol in Myocardial Infarction |
| title_full | Novel Insights into the Cardioprotective Effects of Calcitriol in Myocardial Infarction |
| title_fullStr | Novel Insights into the Cardioprotective Effects of Calcitriol in Myocardial Infarction |
| title_full_unstemmed | Novel Insights into the Cardioprotective Effects of Calcitriol in Myocardial Infarction |
| title_short | Novel Insights into the Cardioprotective Effects of Calcitriol in Myocardial Infarction |
| title_sort | novel insights into the cardioprotective effects of calcitriol in myocardial infarction |
| topic | calcitriol vitamin D myocardial infarction cardiovascular disease cardiac inflammation and remodeling NF-κB |
| url | https://www.mdpi.com/2073-4409/11/10/1676 |
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