Fucoidan modulates SIRT1 and NLRP3 to alleviate hypertensive retinopathy: in vivo and in vitro insights
Abstract Background Hypertension influences the inflammatory pathological changes in the retina. The function of the inflammasomes is significant. To see if Sirtuin 1 (SIRT1) regulates angiotensin II (Ang II)-induced hypertensive retinopathy and inflammation by modulating NOD-like receptor thermal p...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-02-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-024-04877-6 |
| _version_ | 1827326366218977280 |
|---|---|
| author | Jing Li Xiaochen Wang Jie Bai Huangzhao Wei Wenbo Wang Shuai Wang |
| author_facet | Jing Li Xiaochen Wang Jie Bai Huangzhao Wei Wenbo Wang Shuai Wang |
| author_sort | Jing Li |
| collection | DOAJ |
| description | Abstract Background Hypertension influences the inflammatory pathological changes in the retina. The function of the inflammasomes is significant. To see if Sirtuin 1 (SIRT1) regulates angiotensin II (Ang II)-induced hypertensive retinopathy and inflammation by modulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation and the potential protective effects of fucoidan (FO) in mouse retinal vascular endothelial cells (mRECs) and mice retina. Methods The diagnosis of hypertensive retinopathy was made after three weeks of Ang II infusion (3000 ng/kg/min). One day prior to the commencement of Ang II infusion, the mice were treatment with NLRP3 inhibitor MCC950 (10 mg/kg/day, intraperitoneal injections) or FO (300 mg/kg/day, oral gavage). A blood pressure was recorded. Hematoxylin and eosin (H&E) staining was used to conduct pathological alterations, dihydroethidium bromide (DHE) was utilized to assess oxidative stress damage in the retina, and fluorescence angiography was used to identify vascular disorders in the eye. Using immunohistochemical labeling, NLRP3 expression was found. Reactive protein and mRNA expression levels in mouse retina and cells were assessed using Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). Results NLRP3 inflammasome activation and SIRT1 decrease were brought about by Ang II infusion. Retinopathy and dysfunction were lessened by MCC950 target-induced NLRP3 inflammasome activation, while overexpression of SIRT1 had the opposite impact on NLRP3 inflammasome activation, indicating that SIRT1 functions as an upstream regulator of NLRP3 activity. FO may improve SIRT1 expression and decrease NLRP3 activation in retinopathy and dysfunction brought on by Ang II, and the effects were consistent across both in vivo and in vitro models. Conclusions SIRT1 adversely regulates the NLRP3 inflammasome pathway, which in turn increases Ang II-induced inflammation and hypertensive retinopathy. FO may mitigate Ang II-induced retinopathy and dysfunction via modulating the expression of SIRT1/NLRP3. This implies practical approaches to the management of hypertensive retinopathy. |
| first_indexed | 2024-03-07T14:43:25Z |
| format | Article |
| id | doaj.art-2800bbb1125b4bfc9710640844dd1425 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-07T14:43:25Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-2800bbb1125b4bfc9710640844dd14252024-03-05T20:06:52ZengBMCJournal of Translational Medicine1479-58762024-02-0122111310.1186/s12967-024-04877-6Fucoidan modulates SIRT1 and NLRP3 to alleviate hypertensive retinopathy: in vivo and in vitro insightsJing Li0Xiaochen Wang1Jie Bai2Huangzhao Wei3Wenbo Wang4Shuai Wang5Department of Ophthalmology, Second Affiliated Hospital of Dalian Medical UniversityDepartment of Ophthalmology, Second Affiliated Hospital of Dalian Medical UniversityDepartment of Public Health Experimental Teaching Center, Dalian Medical UniversityDalian Institute of Chemical Physics, Chinese Academy of SciencesDepartment of Ophthalmology, Second Affiliated Hospital of Dalian Medical UniversityDepartment of Ophthalmology, Second Affiliated Hospital of Dalian Medical UniversityAbstract Background Hypertension influences the inflammatory pathological changes in the retina. The function of the inflammasomes is significant. To see if Sirtuin 1 (SIRT1) regulates angiotensin II (Ang II)-induced hypertensive retinopathy and inflammation by modulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation and the potential protective effects of fucoidan (FO) in mouse retinal vascular endothelial cells (mRECs) and mice retina. Methods The diagnosis of hypertensive retinopathy was made after three weeks of Ang II infusion (3000 ng/kg/min). One day prior to the commencement of Ang II infusion, the mice were treatment with NLRP3 inhibitor MCC950 (10 mg/kg/day, intraperitoneal injections) or FO (300 mg/kg/day, oral gavage). A blood pressure was recorded. Hematoxylin and eosin (H&E) staining was used to conduct pathological alterations, dihydroethidium bromide (DHE) was utilized to assess oxidative stress damage in the retina, and fluorescence angiography was used to identify vascular disorders in the eye. Using immunohistochemical labeling, NLRP3 expression was found. Reactive protein and mRNA expression levels in mouse retina and cells were assessed using Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). Results NLRP3 inflammasome activation and SIRT1 decrease were brought about by Ang II infusion. Retinopathy and dysfunction were lessened by MCC950 target-induced NLRP3 inflammasome activation, while overexpression of SIRT1 had the opposite impact on NLRP3 inflammasome activation, indicating that SIRT1 functions as an upstream regulator of NLRP3 activity. FO may improve SIRT1 expression and decrease NLRP3 activation in retinopathy and dysfunction brought on by Ang II, and the effects were consistent across both in vivo and in vitro models. Conclusions SIRT1 adversely regulates the NLRP3 inflammasome pathway, which in turn increases Ang II-induced inflammation and hypertensive retinopathy. FO may mitigate Ang II-induced retinopathy and dysfunction via modulating the expression of SIRT1/NLRP3. This implies practical approaches to the management of hypertensive retinopathy.https://doi.org/10.1186/s12967-024-04877-6Hypertensive retinopathySIRT1NLRP3 inflammasomeFucoidan therapeutic potential |
| spellingShingle | Jing Li Xiaochen Wang Jie Bai Huangzhao Wei Wenbo Wang Shuai Wang Fucoidan modulates SIRT1 and NLRP3 to alleviate hypertensive retinopathy: in vivo and in vitro insights Journal of Translational Medicine Hypertensive retinopathy SIRT1 NLRP3 inflammasome Fucoidan therapeutic potential |
| title | Fucoidan modulates SIRT1 and NLRP3 to alleviate hypertensive retinopathy: in vivo and in vitro insights |
| title_full | Fucoidan modulates SIRT1 and NLRP3 to alleviate hypertensive retinopathy: in vivo and in vitro insights |
| title_fullStr | Fucoidan modulates SIRT1 and NLRP3 to alleviate hypertensive retinopathy: in vivo and in vitro insights |
| title_full_unstemmed | Fucoidan modulates SIRT1 and NLRP3 to alleviate hypertensive retinopathy: in vivo and in vitro insights |
| title_short | Fucoidan modulates SIRT1 and NLRP3 to alleviate hypertensive retinopathy: in vivo and in vitro insights |
| title_sort | fucoidan modulates sirt1 and nlrp3 to alleviate hypertensive retinopathy in vivo and in vitro insights |
| topic | Hypertensive retinopathy SIRT1 NLRP3 inflammasome Fucoidan therapeutic potential |
| url | https://doi.org/10.1186/s12967-024-04877-6 |
| work_keys_str_mv | AT jingli fucoidanmodulatessirt1andnlrp3toalleviatehypertensiveretinopathyinvivoandinvitroinsights AT xiaochenwang fucoidanmodulatessirt1andnlrp3toalleviatehypertensiveretinopathyinvivoandinvitroinsights AT jiebai fucoidanmodulatessirt1andnlrp3toalleviatehypertensiveretinopathyinvivoandinvitroinsights AT huangzhaowei fucoidanmodulatessirt1andnlrp3toalleviatehypertensiveretinopathyinvivoandinvitroinsights AT wenbowang fucoidanmodulatessirt1andnlrp3toalleviatehypertensiveretinopathyinvivoandinvitroinsights AT shuaiwang fucoidanmodulatessirt1andnlrp3toalleviatehypertensiveretinopathyinvivoandinvitroinsights |