Proteomics of Mouse Heart Ventricles Reveals Mitochondria and Metabolism as Major Targets of a Post-Infarction Short-Acting GLP1Ra-Therapy.
Proteomics of Mouse Heart Ventricles Reveals Mitochondria and Metabolism as Major Targets of a Post-Infarction Short-Acting GLP1Ra-Therapy.
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DOI：
10.3390/ijms22168711
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发表时间：
2021-08-13
影响因子：
5.6
通讯作者：
Gottlieb RA
中科院分区：
文献类型：
--
作者：
de Freitas Germano J;Sharma A;Stastna M;Huang C;Aniag M;Aceves A;Van Eyk JE;Mentzer RM Jr;Piplani H;Andres AM;Gottlieb RA
心血管疾病是全球死亡的主要原因，因此寻找新的治疗方法以减轻心脏缺血发作后的主要不良心脏事件（MACE）至关重要。胰高血糖素样肽-1受体激动剂（GLP 1 Ra）类药物已证明对心脏功能有益，并降低糖尿病患者MACE的发生率。先前，我们证明了称为DMB（2-喹喔啉胺，6，7-二氯-N-[1，1-二甲基乙基]-3-[甲磺酰基]-1，6，7-二氯-2-甲磺酰基-3-N-叔丁基氨基喹喔啉或化合物2，Sigma）的短效GLP 1 Ra也通过激活梗死后parkin介导的线粒体自噬来减轻瘦小鼠的不良梗死后左心室重塑和心功能障碍。在这里，我们结合蛋白质组学与计算机分析，以表征在整个早期梗死后重塑过程中，DMB在体内的作用范围。我们证明，该化合物是DMB和线粒体呼吸的关键目标，氧化磷酸化和代谢过程，如糖酵解和脂肪酸β-氧化是心脏中该化合物调节的主要生物过程。此外，通过蛋白质-蛋白质相互作用网络鉴定的具有枢纽性质的蛋白质的过表达，例如Atp 2a 2，也可能对DMB的作用机制很重要。数据可通过ProteomeXchange获得，标识符为PXD 027867。
Cardiovascular disease is the main cause of death worldwide, making it crucial to search for new therapies to mitigate major adverse cardiac events (MACEs) after a cardiac ischemic episode. Drugs in the class of the glucagon-like peptide-1 receptor agonists (GLP1Ra) have demonstrated benefits for heart function and reduced the incidence of MACE in patients with diabetes. Previously, we demonstrated that a short-acting GLP1Ra known as DMB (2-quinoxalinamine, 6,7-dichloro-N-[1,1-dimethylethyl]-3-[methylsulfonyl]-,6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline or compound 2, Sigma) also mitigates adverse postinfarction left ventricular remodeling and cardiac dysfunction in lean mice through activation of parkin-mediated mitophagy following infarction. Here, we combined proteomics with in silico analysis to characterize the range of effects of DMB in vivo throughout the course of early postinfarction remodeling. We demonstrate that the mitochondrion is a key target of DMB and mitochondrial respiration, oxidative phosphorylation and metabolic processes such as glycolysis and fatty acid beta-oxidation are the main biological processes being regulated by this compound in the heart. Moreover, the overexpression of proteins with hub properties identified by protein–protein interaction networks, such as Atp2a2, may also be important to the mechanism of action of DMB. Data are available via ProteomeXchange with identifier PXD027867.
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影响因子：
2.1
作者：
Galli A;Lombardi F
通讯作者：
Lombardi F
影响因子：
20.1
作者：
Doenst T;Nguyen TD;Abel ED
通讯作者：
Abel ED
微管相关蛋白 Tau 具有心血管功能的证据
影响因子：
4
作者：
Betrie, Ashenafi H.;Ayton, Scott;Wright, Christine E.
通讯作者：
Wright, Christine E.
影响因子：
3.4
作者：
Qiao H;Ren H;Du H;Zhang M;Xiong X;Lv R
通讯作者：
Lv R
DOI：
10.1056/nejmoa1603827
发表时间：
2016-07-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Marso SP;Daniels GH;Brown-Frandsen K;Kristensen P;Mann JF;Nauck MA;Nissen SE;Pocock S;Poulter NR;Ravn LS;Steinberg WM;Stockner M;Zinman B;Bergenstal RM;Buse JB;LEADER Steering Committee;LEADER Trial Investigators
通讯作者：
LEADER Trial Investigators