A GLP-1 Analog Liraglutide Reduces Intimal Hyperplasia After Coronary Stent Implantation via Regulation of Glycemic Variability and NLRP3 Inflammasome/IL-10 Signaling in Diabetic Swine
ObjectiveThis study aimed to explore whether treatment with the glucagon-like peptide-1 (GLP-1) analog liraglutide reduces intimal hyperplasia after coronary stent implantation via regulation of glycemic variability, the NLRP3 inflammasome, and IL-10 in diabetic swine.MethodsFifteen pigs were divide...
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00372/full |
| _version_ | 1819076965708070912 |
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| author | Jinggang Xia Qinxue Li Yayun Liu Quanxin Ren Jinhuan Gao Yi Tian Jubo Li Baojie Zhang Haichen Sun Shuang Liu |
| author_facet | Jinggang Xia Qinxue Li Yayun Liu Quanxin Ren Jinhuan Gao Yi Tian Jubo Li Baojie Zhang Haichen Sun Shuang Liu |
| author_sort | Jinggang Xia |
| collection | DOAJ |
| description | ObjectiveThis study aimed to explore whether treatment with the glucagon-like peptide-1 (GLP-1) analog liraglutide reduces intimal hyperplasia after coronary stent implantation via regulation of glycemic variability, the NLRP3 inflammasome, and IL-10 in diabetic swine.MethodsFifteen pigs were divided into a diabetes mellitus (DM) group (n = 6), a DM + liraglutide treatment group (L group) (n = 6) and a sham group (n = 3). A total of 24 everolimus-eluting stents were implanted in the left anterior descending and right coronary arteries at 3 weeks. A novel continuous glucose monitoring system (GMS) was used for 2 weeks. The means and standard deviations (SDs) were measured and calculated by the GMS. At 22 weeks, the lumen area (LA), neointimal thickness (NIT), neointimal area (NIA), and percent area stenosis (%AS) were analyzed by optical coherence tomography. Plasma tumor necrosis factor-α, interleukin-6, and interleukin-10 were assayed by ELISA. The intima protein expression levels of NLRP3, interleukin-1β, interleukin-18 and interleukin-10 were examined using Western blot analysis. Histology was used to evaluate the healing response. In an in vitro study, THP-1 cells were divided into control, high glucose (HG), HG + liraglutide, and HG + liraglutide + Exe(9–39) (a GLP-1 receptor inhibitor) groups.ResultsThe L group had a lower SD, NIT, NIA, and %AS; a larger LA; reduced inflammation and injury scores; lower expression levels of tumor necrosis factor-α, interleukin-6, NLRP3, interleukin-1β, and interleukin-18; and higher expression of interleukin-10 compared with those of the DM group (p < 0.05). In the in vitro study, similar results were obtained in the HG + liraglutide group, and Exe(9–39) abolished the effect of liraglutide (p < 0.05).ConclusionsLiraglutide treatment reduces intimal hyperplasia after stent implantation via regulation of glycemic variability, the NLRP3 inflammasome, and IL-10 in diabetic pigs in a GLP-1 receptor-dependent manner. Reducing the inflammation induced by glycemic variability may be one of the cardioprotective mechanisms of liraglutide. |
| first_indexed | 2024-12-21T18:49:41Z |
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| id | doaj.art-e68cbc078a8448ebb7a976ec6d1af659 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-21T18:49:41Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-e68cbc078a8448ebb7a976ec6d1af6592022-12-21T18:53:47ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-03-011110.3389/fphar.2020.00372517719A GLP-1 Analog Liraglutide Reduces Intimal Hyperplasia After Coronary Stent Implantation via Regulation of Glycemic Variability and NLRP3 Inflammasome/IL-10 Signaling in Diabetic SwineJinggang Xia0Qinxue Li1Yayun Liu2Quanxin Ren3Jinhuan Gao4Yi Tian5Jubo Li6Baojie Zhang7Haichen Sun8Shuang Liu9Department of Cardiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, ChinaDepartment of Cardiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, ChinaDepartment of Cardiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, ChinaBeijing Fangshan District Liangxiang Hospital, Beijing, ChinaDepartment of Cardiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, ChinaBeijing Anzhen Hospital, Capital Medical University, Beijing, ChinaDepartment of Animal Experimental Center, Fuwai Hospital, National Center for Cardiovascular Disease, China Academy of Medical Sciences, Beijing, ChinaDepartment of Animal Experimental Center, Fuwai Hospital, National Center for Cardiovascular Disease, China Academy of Medical Sciences, Beijing, ChinaSurgical Laboratory, Xuanwu Hospital, Capital Medical University, Beijing, ChinaSurgical Laboratory, Xuanwu Hospital, Capital Medical University, Beijing, ChinaObjectiveThis study aimed to explore whether treatment with the glucagon-like peptide-1 (GLP-1) analog liraglutide reduces intimal hyperplasia after coronary stent implantation via regulation of glycemic variability, the NLRP3 inflammasome, and IL-10 in diabetic swine.MethodsFifteen pigs were divided into a diabetes mellitus (DM) group (n = 6), a DM + liraglutide treatment group (L group) (n = 6) and a sham group (n = 3). A total of 24 everolimus-eluting stents were implanted in the left anterior descending and right coronary arteries at 3 weeks. A novel continuous glucose monitoring system (GMS) was used for 2 weeks. The means and standard deviations (SDs) were measured and calculated by the GMS. At 22 weeks, the lumen area (LA), neointimal thickness (NIT), neointimal area (NIA), and percent area stenosis (%AS) were analyzed by optical coherence tomography. Plasma tumor necrosis factor-α, interleukin-6, and interleukin-10 were assayed by ELISA. The intima protein expression levels of NLRP3, interleukin-1β, interleukin-18 and interleukin-10 were examined using Western blot analysis. Histology was used to evaluate the healing response. In an in vitro study, THP-1 cells were divided into control, high glucose (HG), HG + liraglutide, and HG + liraglutide + Exe(9–39) (a GLP-1 receptor inhibitor) groups.ResultsThe L group had a lower SD, NIT, NIA, and %AS; a larger LA; reduced inflammation and injury scores; lower expression levels of tumor necrosis factor-α, interleukin-6, NLRP3, interleukin-1β, and interleukin-18; and higher expression of interleukin-10 compared with those of the DM group (p < 0.05). In the in vitro study, similar results were obtained in the HG + liraglutide group, and Exe(9–39) abolished the effect of liraglutide (p < 0.05).ConclusionsLiraglutide treatment reduces intimal hyperplasia after stent implantation via regulation of glycemic variability, the NLRP3 inflammasome, and IL-10 in diabetic pigs in a GLP-1 receptor-dependent manner. Reducing the inflammation induced by glycemic variability may be one of the cardioprotective mechanisms of liraglutide.https://www.frontiersin.org/article/10.3389/fphar.2020.00372/fullliraglutideintimal hyperplasiaglycemic variabilityNOD-like receptor family pyrin domain containing 3interleukin-10 |
| spellingShingle | Jinggang Xia Qinxue Li Yayun Liu Quanxin Ren Jinhuan Gao Yi Tian Jubo Li Baojie Zhang Haichen Sun Shuang Liu A GLP-1 Analog Liraglutide Reduces Intimal Hyperplasia After Coronary Stent Implantation via Regulation of Glycemic Variability and NLRP3 Inflammasome/IL-10 Signaling in Diabetic Swine Frontiers in Pharmacology liraglutide intimal hyperplasia glycemic variability NOD-like receptor family pyrin domain containing 3 interleukin-10 |
| title | A GLP-1 Analog Liraglutide Reduces Intimal Hyperplasia After Coronary Stent Implantation via Regulation of Glycemic Variability and NLRP3 Inflammasome/IL-10 Signaling in Diabetic Swine |
| title_full | A GLP-1 Analog Liraglutide Reduces Intimal Hyperplasia After Coronary Stent Implantation via Regulation of Glycemic Variability and NLRP3 Inflammasome/IL-10 Signaling in Diabetic Swine |
| title_fullStr | A GLP-1 Analog Liraglutide Reduces Intimal Hyperplasia After Coronary Stent Implantation via Regulation of Glycemic Variability and NLRP3 Inflammasome/IL-10 Signaling in Diabetic Swine |
| title_full_unstemmed | A GLP-1 Analog Liraglutide Reduces Intimal Hyperplasia After Coronary Stent Implantation via Regulation of Glycemic Variability and NLRP3 Inflammasome/IL-10 Signaling in Diabetic Swine |
| title_short | A GLP-1 Analog Liraglutide Reduces Intimal Hyperplasia After Coronary Stent Implantation via Regulation of Glycemic Variability and NLRP3 Inflammasome/IL-10 Signaling in Diabetic Swine |
| title_sort | glp 1 analog liraglutide reduces intimal hyperplasia after coronary stent implantation via regulation of glycemic variability and nlrp3 inflammasome il 10 signaling in diabetic swine |
| topic | liraglutide intimal hyperplasia glycemic variability NOD-like receptor family pyrin domain containing 3 interleukin-10 |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00372/full |
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