{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:28:51Z","timestamp":1791246531001,"version":"4.1.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T00:00:00Z","timestamp":1586736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T00:00:00Z","timestamp":1586736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770436"],"award-info":[{"award-number":["81770436"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Project of Chronic Non-Communicable Diseases of China","award":["2016 YFC1300403"],"award-info":[{"award-number":["2016 YFC1300403"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J. of Cardiovasc. Trans. Res."],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chaperone-mediated autophagy (CMA) serves as a critical upstream regulator of lipophagy and lipid metabolism in hepatocyte. However, the role of CMA in lipid metabolism of macrophage, the typical component of atherosclerotic plaque, remains unclear. In our study, LAMP-2A (L2A, a CMA marker) was reduced in macrophages exposed to high dose of oleate, and lipophagy was impaired in advanced atherosclerosis in ApoE (\u2212\/\u2212) mice. Primary peritoneal macrophages isolated from macrophage-specific L2A-deficient mice exhibited pronounced intracellular lipid accumulation. Lipid regulatory enzymes, including long-chain-fatty-acid-CoA ligase 1 (ACSL1) and lysosomal acid lipase (LAL), were increased and reduced in L2A-KO macrophage, respectively. Other lipid-related proteins, such as SR-A, SR-B (CD36), ABCA1, or PLIN2, were not associated with increased lipid content in L2A-KO macrophage. In conclusion, deficient CMA promotes lipid accumulation in macrophage probably by regulating enzymes involved in lipid metabolism. CMA may represent a novel therapeutic target to alleviate atherosclerosis by promoting lipid metabolism.<\/jats:p>","DOI":"10.1007\/s12265-020-09986-3","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T13:02:31Z","timestamp":1586782951000},"page":"661-669","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Deficient Chaperone-Mediated Autophagy Promotes Lipid Accumulation in Macrophage"],"prefix":"10.1007","volume":"14","author":[{"given":"Lei","family":"Qiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He-feng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-qiong","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-xia","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-qiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,13]]},"reference":[{"key":"9986_CR1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1146\/annurev.bi.52.070183.001255","volume":"52","author":"MS Brown","year":"1983","unstructured":"Brown, M. S., & Goldstein, J. L. (1983). Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annual Review of Biochemistry, 52, 223\u2013261.","journal-title":"Annual Review of Biochemistry"},{"key":"9986_CR2","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1038\/nature07976","volume":"458","author":"R Singh","year":"2009","unstructured":"Singh, R., Kaushik, S., Wang, Y., Xiang, Y., Novak, I., Komatsu, M., Tanaka, K., Cuervo, A. M., & Czaja, M. J. (2009). Autophagy regulates lipid metabolism. Nature., 458, 1131\u20131135.","journal-title":"Nature."},{"key":"9986_CR3","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.cmet.2011.03.023","volume":"13","author":"M Ouimet","year":"2011","unstructured":"Ouimet, M., Franklin, V., Mak, E., Liao, X., Tabas, I., & Marcel, Y. L. (2011). Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase. Cell Metabolism, 13, 655\u2013667.","journal-title":"Cell Metabolism"},{"key":"9986_CR4","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1016\/j.devcel.2009.05.001","volume":"16","author":"H Weidberg","year":"2009","unstructured":"Weidberg, H., Shvets, E., & Elazar, Z. (2009). Lipophagy: selective catabolism designed for lipids. Developmental Cell, 16, 628\u2013630.","journal-title":"Developmental Cell"},{"key":"9986_CR5","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/s41580-018-0001-6","volume":"19","author":"S Kaushik","year":"2018","unstructured":"Kaushik, S., & Cuervo, A. M. (2018). The coming of age of chaperone-mediated autophagy. Nature Reviews. Molecular Cell Biology, 19, 365\u2013381.","journal-title":"Nature Reviews. Molecular Cell Biology"},{"key":"9986_CR6","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1038\/ncb3166","volume":"17","author":"S Kaushik","year":"2015","unstructured":"Kaushik, S., & Cuervo, A. M. (2015). Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis. Nature Cell Biology, 17, 759\u2013770.","journal-title":"Nature Cell Biology"},{"key":"9986_CR7","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cmet.2014.06.009","volume":"20","author":"JL Schneider","year":"2014","unstructured":"Schneider, J. L., Suh, Y., & Cuervo, A. M. (2014). Deficient chaperone-mediated autophagy in liver leads to metabolic dysregulation. Cell Metabolism, 20, 417\u2013432.","journal-title":"Cell Metabolism"},{"key":"9986_CR8","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1161\/01.ATV.14.1.133","volume":"14","author":"Y Nakashima","year":"1994","unstructured":"Nakashima, Y., Plump, A. S., Raines, E. W., Breslow, J. L., & Ross, R. (1994). ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arteriosclerosis and Thrombosis, 14, 133\u2013140.","journal-title":"Arteriosclerosis and Thrombosis"},{"key":"9986_CR9","doi-asserted-by":"publisher","first-page":"2290","DOI":"10.1096\/fj.201801267RR","volume":"33","author":"C Wang","year":"2019","unstructured":"Wang, C., Xu, W., Liang, M., Huang, D., & Huang, K. (2019). CTRP13 inhibits atherosclerosis via autophagy-lysosome-dependent degradation of CD36. The FASEB Journal, 33, 2290\u20132300.","journal-title":"The FASEB Journal"},{"key":"9986_CR10","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.jnutbio.2018.02.017","volume":"57","author":"R Varshney","year":"2018","unstructured":"Varshney, R., Varshney, R., Mishra, R., Gupta, S., Sircar, D., & Roy, P. (2018). Kaempferol alleviates palmitic acid-induced lipid stores, endoplasmic reticulum stress and pancreatic \u03b2-cell dysfunction through AMPK\/mTOR-mediated lipophagy. The Journal of Nutritional Biochemistry, 57, 212\u2013227.","journal-title":"The Journal of Nutritional Biochemistry"},{"key":"9986_CR11","doi-asserted-by":"publisher","first-page":"42841","DOI":"10.1074\/jbc.M506569200","volume":"280","author":"G Xu","year":"2005","unstructured":"Xu, G., Sztalryd, C., Lu, X., Tansey, J. T., Gan, J., Dorward, H., Kimmel, A. R., & Londos, C. (2005). Post-translational regulation of adipose differentiation-related protein by the ubiquitin\/proteasome pathway. The Journal of Biological Chemistry, 280, 42841\u201342847.","journal-title":"The Journal of Biological Chemistry"},{"key":"9986_CR12","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1111\/j.1749-6632.2000.tb06306.x","volume":"902","author":"TJ Van Berkel","year":"2000","unstructured":"Van Berkel, T. J., Van Eck, M., Herijgers, N., Fluiter, K., & Nion, S. (2000). Scavenger receptor classes A and B. Their roles in atherogenesis and the metabolism of modified LDL and HDL. Ann N Y Acad Sci, 902, 113\u2013126.","journal-title":"Ann N Y Acad Sci"},{"key":"9986_CR13","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1111\/j.1749-6632.2001.tb03944.x","volume":"947","author":"AC Nicholson","year":"2001","unstructured":"Nicholson, A. C., Han, J., Febbraio, M., Silversterin, R. L., & Hajjar, D. P. (2001). Role of CD36, the macrophage class B scavenger receptor, in atherosclerosis. Annals of the New York Academy of Sciences, 947, 224\u2013228.","journal-title":"Annals of the New York Academy of Sciences"},{"key":"9986_CR14","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.tibs.2007.02.001","volume":"32","author":"AD Attie","year":"2007","unstructured":"Attie, A. D. (2007). ABCA1: At the nexus of cholesterol, HDL and atherosclerosis. Trends Biochem Sci, 32, 172\u2013179.","journal-title":"Trends Biochem Sci"},{"key":"9986_CR15","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1152\/ajpendo.00112.2006","volume":"291","author":"HA Parkes","year":"2006","unstructured":"Parkes, H. A., Preston, E., Wilks, D., Ballesteros, M., Carpenter, L., Wood, L., Kraegen, E. W., Furler, S. M., & Cooney, G. L. (2006). Overexpression of acyl-CoA synthetase-1 increases lipid deposition in hepatic (HepG2) cells and rodent liver in vivo. American Journal of Physiology. Endocrinology and Metabolism, 291, 737\u2013744.","journal-title":"American Journal of Physiology. Endocrinology and Metabolism"},{"key":"9986_CR16","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.tips.2018.12.006","volume":"40","author":"M Gomaraschi","year":"2019","unstructured":"Gomaraschi, M., Bonacina, F., & Norata, G. D. (2019). Lysosomal acid lipase: from cellular lipid handler to immunometabolic target. Trends in Pharmacological Sciences, 40, 104\u2013115.","journal-title":"Trends in Pharmacological Sciences"},{"key":"9986_CR17","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.cmet.2015.06.017","volume":"22","author":"M Schweiger","year":"2015","unstructured":"Schweiger, M., & Zechner, R. (2015). Breaking the barrier\u2014chaperone-mediated autophagy of perilipins regulates the lipolytic degradation of fat. Cell Metabolism, 22, 60\u201361.","journal-title":"Cell Metabolism"},{"key":"9986_CR18","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1007\/978-981-15-0602-4_20","volume":"1206","author":"Q Yang","year":"2019","unstructured":"Yang, Q., Wang, R., & Zhu, L. (2019). Chaperone-mediated autophagy. Adv Exp Med Biol, 1206, 435\u2013452.","journal-title":"Adv Exp Med Biol"},{"key":"9986_CR19","doi-asserted-by":"publisher","first-page":"282041","DOI":"10.1155\/2012\/282041","volume":"2012","author":"R Singh","year":"2012","unstructured":"Singh, R., & Cuervo, A. M. (2012). Lipophagy:connecting autophagy and lipid metabolism. Int J Cell Biol., 2012, 282041.","journal-title":"Int J Cell Biol."},{"key":"9986_CR20","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1161\/ATVBAHA.111.240705","volume":"32","author":"M Ouimet","year":"2012","unstructured":"Ouimet, M., & Marcel, Y. L. (2012). Regulation of lipid droplet cholesterol efflux from macrophage foam cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 32, 575\u2013581.","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"9986_CR21","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1089\/104303402760128586","volume":"13","author":"H Du","year":"2002","unstructured":"Du, H., Heur, M., Witte, D. P., Ameis, D., & Grabowski, G. A. (2002). Lysosomal acid lipase deficiency: correction of lipid storage by adenovirus-mediated gene transfer in mice. Human Gene Therapy, 13, 1361\u20131372.","journal-title":"Human Gene Therapy"}],"container-title":["Journal of Cardiovascular Translational Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12265-020-09986-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12265-020-09986-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12265-020-09986-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T11:17:31Z","timestamp":1630063051000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12265-020-09986-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,13]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["9986"],"URL":"https:\/\/doi.org\/10.1007\/s12265-020-09986-3","relation":{},"ISSN":["1937-5387","1937-5395"],"issn-type":[{"value":"1937-5387","type":"print"},{"value":"1937-5395","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,13]]},"assertion":[{"value":"14 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 April 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"All applicable international, national, and\/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were approved by the Ethical Committee of Qilu Hospital of Shandong University. This article does not contain any studies with human participants performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}