Liraglutide Attenuates Aortic Valve Calcification in a High-Cholesterol-Diet-Induced Experimental Calcific Aortic Valve Disease Model in Apolipoprotein E-Deficient Mice.
Liraglutide Attenuates Aortic Valve Calcification in a High-Cholesterol-Diet-Induced Experimental Calcific Aortic Valve Disease Model in Apolipoprotein E-Deficient Mice.
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DOI：
10.3390/jcdd10090386
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发表时间：
2023-09-06
影响因子：
2.4
通讯作者：
中科院分区：
文献类型：
--
作者：
背景：主动脉瓣钙化病（CAVD）是老年人发病和死亡的重要原因。然而，没有有效的药物被批准减缓或预防CAVD的进展。在这里，我们检查了利拉鲁肽对主动脉瓣狭窄的影响。方法：用高胆固醇饮食喂养雄性Apoe - / -小鼠24周，建立实验性CAVD模型，随机分为利拉鲁肽治疗组和对照组。超声心动图和免疫组织学分析检查主动脉瓣功能和形态、纤维化和钙沉积。通过ELISA、FACS和免疫荧光检测血浆胰高血糖素样肽-1 （GLP-1）水平和炎症含量。RNA测序（RNA-seq）用于鉴定利拉鲁肽影响的途径和过程。结果：CAVD模型血浆GLP-1水平降低，利拉鲁肽治疗可显著改善主动脉瓣钙化和功能，减轻炎症。RNA-seq显示利拉鲁肽影响主动脉瓣的多种肌成纤维细胞和成骨分化或炎症相关的生物学状态或过程。利拉鲁肽介导的有益作用与GLP-1受体（GLP-1R）表达增加有关。结论：利拉鲁肽可阻断主动脉瓣钙化，可作为CAVD治疗的潜在治疗药物。
Background: Calcific aortic valve disease (CAVD) is a significant cause of morbidity and mortality among elderly people. However, no effective medications have been approved to slow or prevent the progression of CAVD. Here, we examined the effect of liraglutide on aortic valve stenosis. Methods: Male Apoe−/− mice were fed with a high-cholesterol diet for 24 weeks to generate an experimental CAVD model and randomly assigned to a liraglutide treatment group or control group. Echocardiography and immunohistological analyses were performed to examine the aortic valve function and morphology, fibrosis, and calcium deposition. Plasma Glucagon-like peptide-1 (GLP-1) levels and inflammatory contents were measured via ELISA, FACS, and immunofluorescence. RNA sequencing (RNA-seq) was used to identify liraglutide-affected pathways and processes. Results: Plasma GLP-1 levels were reduced in the CAVD model, and liraglutide treatment significantly improved aortic valve calcification and functions and attenuated inflammation. RNA-seq showed that liraglutide affects multiple myofibroblastic and osteogenic differentiations or inflammation-associated biological states or processes in the aortic valve. Those liraglutide-mediated beneficial effects were associated with increased GLP-1 receptor (GLP-1R) expression. Conclusions: Liraglutide blocks aortic valve calcification and may serve as a potential therapeutic drug for CAVD treatment.
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影响因子：
37.8
作者：
Go AS;Mozaffarian D;Roger VL;Benjamin EJ;Berry JD;Blaha MJ;Dai S;Ford ES;Fox CS;Franco S;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Huffman MD;Judd SE;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Mackey RH;Magid DJ;Marcus GM;Marelli A;Matchar DB;McGuire DK;Mohler ER 3rd;Moy CS;Mussolino ME;Neumar RW;Nichol G;Pandey DK;Paynter NP;Reeves MJ;Sorlie PD;Stein J;Towfighi A;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
利拉鲁肽通过调节 AMPK/mTOR 信号减弱 MC3T3-E1 细胞的成骨细胞分化
影响因子：
3.4
作者：
Hu XK;Yin XH;Zhang HQ;Guo CF;Tang MX
通讯作者：
Tang MX
影响因子：
37.8
作者：
Lindman BR;Merryman WD
通讯作者：
Merryman WD
影响因子：
1.6
作者：
Panchal A;Kyvernitakis A;Rayarao G;Doyle M;Biederman RWW
通讯作者：
Biederman RWW
影响因子：
158.5
作者：
Cowell, SJ;Newby, DE;Boon, NA
通讯作者：
Boon, NA