Storax Attenuates Cardiac Fibrosis following Acute Myocardial Infarction in Rats via Suppression of AT1R–Ankrd1–P53 Signaling Pathway
Myocardial fibrosis following acute myocardial infarction (AMI) seriously affects the prognosis and survival rate of patients. This study explores the role and regulation mechanism of storax, a commonly used traditional Chinese medicine for treatment of cardiovascular diseases, on myocardial fibrosi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/21/13161 |
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| author | Zhuo Xu Danni Lu Jianmei Yuan Liying Wang Jiajun Wang Ziqin Lei Si Liu Junjie Wu Jian Wang Lihua Huang |
| author_facet | Zhuo Xu Danni Lu Jianmei Yuan Liying Wang Jiajun Wang Ziqin Lei Si Liu Junjie Wu Jian Wang Lihua Huang |
| author_sort | Zhuo Xu |
| collection | DOAJ |
| description | Myocardial fibrosis following acute myocardial infarction (AMI) seriously affects the prognosis and survival rate of patients. This study explores the role and regulation mechanism of storax, a commonly used traditional Chinese medicine for treatment of cardiovascular diseases, on myocardial fibrosis and cardiac function. The AMI rat model was established by subcutaneous injection of Isoproterenol hydrochloride (ISO). Storax (0.1, 0.2, 0.4 g/kg) was administered by gavage once/d for 7 days. Electrocardiogram, echocardiography, hemodynamic and cardiac enzyme in AMI rats were measured. HE, Masson, immunofluorescence and TUNEL staining were used to observe the degree of pathological damage, fibrosis and cardiomyocyte apoptosis in myocardial tissue, respectively. Expression of AT1R, CARP and their downstream related apoptotic proteins were detected by WB. The results demonstrated that storax could significantly improve cardiac electrophysiology and function, decrease serum cardiac enzyme activity, reduce type I and III collagen contents to improve fibrosis and alleviate myocardial pathological damage and cardiomyocyte apoptosis. It also found that storax can significantly down-regulate expression of AT1R, Ankrd1, P53, P-p53 (ser 15), Bax and cleaved Caspase-3 and up-regulate expression of Mdm2 and Bcl-2. Taken together, these findings indicated that storax effectively protected cardiomyocytes against myocardial fibrosis and cardiac dysfunction by inhibiting the AT1R–Ankrd1–P53 signaling pathway. |
| first_indexed | 2024-03-09T19:00:43Z |
| format | Article |
| id | doaj.art-811d930ff2fe458281eb5b39d4d5a390 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:00:43Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-811d930ff2fe458281eb5b39d4d5a3902023-11-24T05:03:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211316110.3390/ijms232113161Storax Attenuates Cardiac Fibrosis following Acute Myocardial Infarction in Rats via Suppression of AT1R–Ankrd1–P53 Signaling PathwayZhuo Xu0Danni Lu1Jianmei Yuan2Liying Wang3Jiajun Wang4Ziqin Lei5Si Liu6Junjie Wu7Jian Wang8Lihua Huang9State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaMyocardial fibrosis following acute myocardial infarction (AMI) seriously affects the prognosis and survival rate of patients. This study explores the role and regulation mechanism of storax, a commonly used traditional Chinese medicine for treatment of cardiovascular diseases, on myocardial fibrosis and cardiac function. The AMI rat model was established by subcutaneous injection of Isoproterenol hydrochloride (ISO). Storax (0.1, 0.2, 0.4 g/kg) was administered by gavage once/d for 7 days. Electrocardiogram, echocardiography, hemodynamic and cardiac enzyme in AMI rats were measured. HE, Masson, immunofluorescence and TUNEL staining were used to observe the degree of pathological damage, fibrosis and cardiomyocyte apoptosis in myocardial tissue, respectively. Expression of AT1R, CARP and their downstream related apoptotic proteins were detected by WB. The results demonstrated that storax could significantly improve cardiac electrophysiology and function, decrease serum cardiac enzyme activity, reduce type I and III collagen contents to improve fibrosis and alleviate myocardial pathological damage and cardiomyocyte apoptosis. It also found that storax can significantly down-regulate expression of AT1R, Ankrd1, P53, P-p53 (ser 15), Bax and cleaved Caspase-3 and up-regulate expression of Mdm2 and Bcl-2. Taken together, these findings indicated that storax effectively protected cardiomyocytes against myocardial fibrosis and cardiac dysfunction by inhibiting the AT1R–Ankrd1–P53 signaling pathway.https://www.mdpi.com/1422-0067/23/21/13161storaxmyocardial infarctioncardiac fibrosiscardiac dysfunctionAT1R–Ankrd1–P53 |
| spellingShingle | Zhuo Xu Danni Lu Jianmei Yuan Liying Wang Jiajun Wang Ziqin Lei Si Liu Junjie Wu Jian Wang Lihua Huang Storax Attenuates Cardiac Fibrosis following Acute Myocardial Infarction in Rats via Suppression of AT1R–Ankrd1–P53 Signaling Pathway International Journal of Molecular Sciences storax myocardial infarction cardiac fibrosis cardiac dysfunction AT1R–Ankrd1–P53 |
| title | Storax Attenuates Cardiac Fibrosis following Acute Myocardial Infarction in Rats via Suppression of AT1R–Ankrd1–P53 Signaling Pathway |
| title_full | Storax Attenuates Cardiac Fibrosis following Acute Myocardial Infarction in Rats via Suppression of AT1R–Ankrd1–P53 Signaling Pathway |
| title_fullStr | Storax Attenuates Cardiac Fibrosis following Acute Myocardial Infarction in Rats via Suppression of AT1R–Ankrd1–P53 Signaling Pathway |
| title_full_unstemmed | Storax Attenuates Cardiac Fibrosis following Acute Myocardial Infarction in Rats via Suppression of AT1R–Ankrd1–P53 Signaling Pathway |
| title_short | Storax Attenuates Cardiac Fibrosis following Acute Myocardial Infarction in Rats via Suppression of AT1R–Ankrd1–P53 Signaling Pathway |
| title_sort | storax attenuates cardiac fibrosis following acute myocardial infarction in rats via suppression of at1r ankrd1 p53 signaling pathway |
| topic | storax myocardial infarction cardiac fibrosis cardiac dysfunction AT1R–Ankrd1–P53 |
| url | https://www.mdpi.com/1422-0067/23/21/13161 |
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