PMID- 30426302 OWN - NLM STAT- MEDLINE DCOM- 20190425 LR - 20211204 IS - 1573-4919 (Electronic) IS - 0300-8177 (Linking) VI - 455 IP - 1-2 DP - 2019 May TI - Overexpression of CTRP9 attenuates the development of atherosclerosis in apolipoprotein E-deficient mice. PG - 99-108 LID - 10.1007/s11010-018-3473-y [doi] AB - This study was aimed to explore the role of C1q/TNF-related protein 9 (CTRP9) on atherosclerotic lesion formation. A recombinant lentiviral vector carrying mouse CTRP9 (Lv-CTRP9) was injected intravenously into apolipoprotein E knockout (ApoE(-/-)) mice given a high-fat diet (HFD). CTRP9 overexpression substantially attenuated atherosclerotic lesion size of mice. The accumulation of macrophages and smooth muscle cells (SMCs) was significantly decreased in atherosclerotic regions with CTRP9 overexpression by immunohistochemical analysis. In addition, CTRP9 downregulated the expressions of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha), two main proinflammatory cytokines in atherosclerosis. Furthermore, the autophagy level remarkably increased which was presented by microtubule-associated protein light chain 3B (LC3B) conversion and sequestosome 1 (SQSTM1/p62) degradation. Further study showed that CTRP9 increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and decreased mammalian target of rapamycin (mTOR) phosphorylation in vivo. These observations reveal that CTRP9 exerts a protecting role in early atherosclerotic lesions and its anti-atherosclerotic effect is associated with autophagy induction through AMPK/mTOR signaling pathway. FAU - Huang, Chengmin AU - Huang C AD - Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. AD - Department of Cardiology, The Affiliated Cardiovascular Hospital of Xiamen University, Xiamen, 361004, Fujian, People's Republic of China. FAU - Zhang, Peng AU - Zhang P AD - Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. AD - Department of Geriatrics, Peking University First Hospital, Beijing, 100034, People's Republic of China. FAU - Li, Tingting AU - Li T AD - Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. AD - Department of General Medicine, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. FAU - Li, Jun AU - Li J AD - Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. FAU - Liu, Tianjiao AU - Liu T AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. FAU - Zuo, Anju AU - Zuo A AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. AD - Department of General Medicine, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. FAU - Chen, Jiying AU - Chen J AD - Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. AD - Department of General Medicine, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. FAU - Guo, Yuan AU - Guo Y AD - Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. guoyuan9092@163.com. AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. guoyuan9092@163.com. AD - Department of General Medicine, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. guoyuan9092@163.com. LA - eng GR - 81671950/National Natural Science Foundation of China/ GR - 2014GSF118020/Department of Science and Technology of Shandong Province/ PT - Journal Article DEP - 20181113 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Adiponectin) RN - 0 (CTRP9 protein, mouse) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Glycoproteins) RN - 0 (Map1lc3b protein, mouse) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Sequestosome-1 Protein) RN - 0 (Sqstm1 protein, mouse) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Adiponectin/*biosynthesis/genetics MH - Animals MH - Atherosclerosis/genetics/*metabolism/pathology MH - Chemokine CCL2/biosynthesis/genetics MH - Glycoproteins/*biosynthesis/genetics MH - Lentivirus MH - Macrophages/*metabolism/pathology MH - Mice MH - Mice, Knockout, ApoE MH - Microtubule-Associated Proteins/genetics/metabolism MH - Myocytes, Smooth Muscle/*metabolism/pathology MH - Phosphorylation/genetics MH - Proteolysis MH - Sequestosome-1 Protein/genetics/metabolism MH - *Signal Transduction MH - TOR Serine-Threonine Kinases/genetics/metabolism MH - Transduction, Genetic MH - Tumor Necrosis Factor-alpha/biosynthesis/genetics OTO - NOTNLM OT - AMPK OT - Atherosclerosis OT - Autophagy OT - CTRP9 OT - mTOR EDAT- 2018/11/15 06:00 MHDA- 2019/04/26 06:00 CRDT- 2018/11/15 06:00 PHST- 2018/04/23 00:00 [received] PHST- 2018/11/09 00:00 [accepted] PHST- 2018/11/15 06:00 [pubmed] PHST- 2019/04/26 06:00 [medline] PHST- 2018/11/15 06:00 [entrez] AID - 10.1007/s11010-018-3473-y [pii] AID - 10.1007/s11010-018-3473-y [doi] PST - ppublish SO - Mol Cell Biochem. 2019 May;455(1-2):99-108. doi: 10.1007/s11010-018-3473-y. Epub 2018 Nov 13.