Tetramethylpyrazine Alleviates Endothelial Glycocalyx Degradation and Promotes Glycocalyx Restoration via TLR4/NF-κB/HPSE1 Signaling Pathway During Inflammation
Tetramethylpyrazine (TMP), a Chinese traditional herbal extraction widely used in treating cardiovascular diseases, could attenuate vascular endothelial injuries, but the underlying mechanism remains incomprehensive. Vascular glycocalyx coating on the endothelium would be damaged and caused endothel...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-01-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.791841/full |
| _version_ | 1798018252213846016 |
|---|---|
| author | Jin Lei Jin Lei Peng Xiang Peng Xiang Shengmei Zeng Shengmei Zeng Le Chen Le Chen Lei Zhang Lei Zhang Zhiyi Yuan Zhiyi Yuan Jun Zhang Jun Zhang Tingting Wang Tingting Wang Ruihong Yu Ruihong Yu Wanping Zhang Wanping Zhang Issa Issoufou Ibrahim Issa Issoufou Ibrahim Limei Ma Limei Ma Chao Yu Chao Yu |
| author_facet | Jin Lei Jin Lei Peng Xiang Peng Xiang Shengmei Zeng Shengmei Zeng Le Chen Le Chen Lei Zhang Lei Zhang Zhiyi Yuan Zhiyi Yuan Jun Zhang Jun Zhang Tingting Wang Tingting Wang Ruihong Yu Ruihong Yu Wanping Zhang Wanping Zhang Issa Issoufou Ibrahim Issa Issoufou Ibrahim Limei Ma Limei Ma Chao Yu Chao Yu |
| author_sort | Jin Lei |
| collection | DOAJ |
| description | Tetramethylpyrazine (TMP), a Chinese traditional herbal extraction widely used in treating cardiovascular diseases, could attenuate vascular endothelial injuries, but the underlying mechanism remains incomprehensive. Vascular glycocalyx coating on the endothelium would be damaged and caused endothelial dysfunction in the inflammatory microenvironment, which was the initial factor of morbidity of many vascular diseases, such as atherosclerosis (AS). Here, we thoroughly investigated the molecular mechanism of TMP on vascular endothelial glycocalyx in the LPS-induced inflammatory model both in vitro and in vivo. Results showed that pretreatment with TMP significantly inhibited glycocalyx degradation and monocytes adhesion to the endothelial process. Moreover, TMP pretreatment inhibited the expression of HPSE1 (a major degrading enzyme of endothelial glycocalyx), Toll-like receptor 4 (TLR4), and the translocation of nuclear factor kappa B p65 (NF-κB p65). We were utilized withTLR4 siRNA, NF-κB inhibitor, and HPSE1 overexpression analysis confirmed TMP’s protection on endothelial glycocalyx injury, which further contributed to the monocyte-endothelial adhesion process. It was indicated that TMP might suppress glycocalyx degradation through TLR4/NF-κB/HPSE1 signaling pathway. Taken together, our results enriched the occurrence molecular mechanism of glycocalyx shedding and molecular regulation mechanism of TMP in protecting integrity of the glycocalyx structure during inflammation. As TMP is currently used in clinical applications, it may be considered a novel strategy against atherosclerosis through its ability to protect endothelial glycocalyx. |
| first_indexed | 2024-04-11T16:20:48Z |
| format | Article |
| id | doaj.art-46f93c3bca824b82ba294745a5bf18ec |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T16:20:48Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-46f93c3bca824b82ba294745a5bf18ec2022-12-22T04:14:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-01-011210.3389/fphar.2021.791841791841Tetramethylpyrazine Alleviates Endothelial Glycocalyx Degradation and Promotes Glycocalyx Restoration via TLR4/NF-κB/HPSE1 Signaling Pathway During InflammationJin Lei0Jin Lei1Peng Xiang2Peng Xiang3Shengmei Zeng4Shengmei Zeng5Le Chen6Le Chen7Lei Zhang8Lei Zhang9Zhiyi Yuan10Zhiyi Yuan11Jun Zhang12Jun Zhang13Tingting Wang14Tingting Wang15Ruihong Yu16Ruihong Yu17Wanping Zhang18Wanping Zhang19Issa Issoufou Ibrahim20Issa Issoufou Ibrahim21Limei Ma22Limei Ma23Chao Yu24Chao Yu25College of Pharmacy, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing, ChinaCollege of Pharmacy, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing, ChinaCollege of Pharmacy, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing, ChinaCollege of Pharmacy, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing, ChinaCollege of Pharmacy, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing, ChinaCollege of Pharmacy, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing, ChinaChongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing, ChinaInstitute of Life Sciences, College of Pharmacy, Chongqing Medical University, Chongqing, ChinaCollege of Pharmacy, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing, ChinaCollege of Pharmacy, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing, ChinaCollege of Pharmacy, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing, ChinaCollege of Pharmacy, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing, ChinaCollege of Pharmacy, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing, ChinaCollege of Pharmacy, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing, ChinaTetramethylpyrazine (TMP), a Chinese traditional herbal extraction widely used in treating cardiovascular diseases, could attenuate vascular endothelial injuries, but the underlying mechanism remains incomprehensive. Vascular glycocalyx coating on the endothelium would be damaged and caused endothelial dysfunction in the inflammatory microenvironment, which was the initial factor of morbidity of many vascular diseases, such as atherosclerosis (AS). Here, we thoroughly investigated the molecular mechanism of TMP on vascular endothelial glycocalyx in the LPS-induced inflammatory model both in vitro and in vivo. Results showed that pretreatment with TMP significantly inhibited glycocalyx degradation and monocytes adhesion to the endothelial process. Moreover, TMP pretreatment inhibited the expression of HPSE1 (a major degrading enzyme of endothelial glycocalyx), Toll-like receptor 4 (TLR4), and the translocation of nuclear factor kappa B p65 (NF-κB p65). We were utilized withTLR4 siRNA, NF-κB inhibitor, and HPSE1 overexpression analysis confirmed TMP’s protection on endothelial glycocalyx injury, which further contributed to the monocyte-endothelial adhesion process. It was indicated that TMP might suppress glycocalyx degradation through TLR4/NF-κB/HPSE1 signaling pathway. Taken together, our results enriched the occurrence molecular mechanism of glycocalyx shedding and molecular regulation mechanism of TMP in protecting integrity of the glycocalyx structure during inflammation. As TMP is currently used in clinical applications, it may be considered a novel strategy against atherosclerosis through its ability to protect endothelial glycocalyx.https://www.frontiersin.org/articles/10.3389/fphar.2021.791841/fullendothelial glycocalyxTMPHPSE1TLR4/NF-κB signaling pathwayLPS |
| spellingShingle | Jin Lei Jin Lei Peng Xiang Peng Xiang Shengmei Zeng Shengmei Zeng Le Chen Le Chen Lei Zhang Lei Zhang Zhiyi Yuan Zhiyi Yuan Jun Zhang Jun Zhang Tingting Wang Tingting Wang Ruihong Yu Ruihong Yu Wanping Zhang Wanping Zhang Issa Issoufou Ibrahim Issa Issoufou Ibrahim Limei Ma Limei Ma Chao Yu Chao Yu Tetramethylpyrazine Alleviates Endothelial Glycocalyx Degradation and Promotes Glycocalyx Restoration via TLR4/NF-κB/HPSE1 Signaling Pathway During Inflammation Frontiers in Pharmacology endothelial glycocalyx TMP HPSE1 TLR4/NF-κB signaling pathway LPS |
| title | Tetramethylpyrazine Alleviates Endothelial Glycocalyx Degradation and Promotes Glycocalyx Restoration via TLR4/NF-κB/HPSE1 Signaling Pathway During Inflammation |
| title_full | Tetramethylpyrazine Alleviates Endothelial Glycocalyx Degradation and Promotes Glycocalyx Restoration via TLR4/NF-κB/HPSE1 Signaling Pathway During Inflammation |
| title_fullStr | Tetramethylpyrazine Alleviates Endothelial Glycocalyx Degradation and Promotes Glycocalyx Restoration via TLR4/NF-κB/HPSE1 Signaling Pathway During Inflammation |
| title_full_unstemmed | Tetramethylpyrazine Alleviates Endothelial Glycocalyx Degradation and Promotes Glycocalyx Restoration via TLR4/NF-κB/HPSE1 Signaling Pathway During Inflammation |
| title_short | Tetramethylpyrazine Alleviates Endothelial Glycocalyx Degradation and Promotes Glycocalyx Restoration via TLR4/NF-κB/HPSE1 Signaling Pathway During Inflammation |
| title_sort | tetramethylpyrazine alleviates endothelial glycocalyx degradation and promotes glycocalyx restoration via tlr4 nf κb hpse1 signaling pathway during inflammation |
| topic | endothelial glycocalyx TMP HPSE1 TLR4/NF-κB signaling pathway LPS |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.791841/full |
| work_keys_str_mv | AT jinlei tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT jinlei tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT pengxiang tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT pengxiang tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT shengmeizeng tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT shengmeizeng tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT lechen tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT lechen tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT leizhang tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT leizhang tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT zhiyiyuan tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT zhiyiyuan tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT junzhang tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT junzhang tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT tingtingwang tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT tingtingwang tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT ruihongyu tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT ruihongyu tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT wanpingzhang tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT wanpingzhang tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT issaissoufouibrahim tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT issaissoufouibrahim tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT limeima tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT limeima tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT chaoyu tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation AT chaoyu tetramethylpyrazinealleviatesendothelialglycocalyxdegradationandpromotesglycocalyxrestorationviatlr4nfkbhpse1signalingpathwayduringinflammation |