{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:16:39Z","timestamp":1791461799443,"version":"4.3.4"},"reference-count":31,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["22K08909"],"award-info":[{"award-number":["22K08909"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Percutaneous ventricular assist devices are utilized in cases of cardiogenic shock following acute myocardial infarction (AMI). However, the mechanism underlying the beneficial effects of LV unloading in AMI remains unclear. This study aimed to examine the impact of LV unloading on cardiac function, heart failure markers, and protein degradation (autophagy and ubiquitin\u2013proteasome system: UPS) post AMI in rats. Nine-week-old male Lewis rats were randomized into non-AMI, AMI, non-AMI with LV unloading, and AMI with LV unloading groups. LV unloading was achieved through heterotopic heart\u2013lung transplantation. Rats were euthanized 2 and 14 days after the procedure. Cardiac functional assessment was performed using Langendorff heart perfusion. RT-PCR and Western blot analyses were conducted using the LV myocardium. The rate pressure product was comparable between the non-AMI with LV unloading group and the AMI with LV unloading at 14 days. The atrial natriuretic factor tended to be suppressed by LV unloading. LV unloading had reducing effects on the expressions of p62, selectively degraded during autophagy, both 2 and 14 days after AMI. There was no effect on the parameters for the UPS. LV unloading has a mitigating effect on the deterioration of cardiac function following AMI. Autophagy, which was suppressed by AMI, was ameliorated by LV unloading.<\/jats:p>","DOI":"10.3390\/ijms26094422","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T11:38:06Z","timestamp":1746531486000},"page":"4422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of Left Ventricular Unloading on Cardiac Function, Heart Failure Markers, and Autophagy in Rat Hearts with Acute Myocardial Infarction"],"prefix":"10.3390","volume":"26","author":[{"given":"Ryota","family":"Azuma","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kitaku, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8471-5166","authenticated-orcid":false,"given":"Yasushige","family":"Shingu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kitaku, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kitaku, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3587-1629","authenticated-orcid":false,"given":"Satoru","family":"Wakasa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kitaku, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1161\/CIR.0000000000001123","article-title":"Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association","volume":"147","author":"Tsao","year":"2023","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/j.jacc.2016.12.005","article-title":"Trends in U.S. Cardiovascular Care: 2016 Report From 4 ACC National Cardiovascular Data Registries","volume":"69","author":"Masoudi","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.1093\/eurheartj\/ehz363","article-title":"Management of cardiogenic shock complicating myocardial infarction: An update 2019","volume":"40","author":"Thiele","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Manzi, L., Sperandeo, L., Forzano, I., Castiello, D.S., Florimonte, D., Paolillo, R., Santoro, C., Mancusi, C., Di Serafino, L., and Esposito, G. (2024). Contemporary Evidence and Practice on Right Heart Catheterization in Patients with Acute or Chronic Heart Failure. Diagnostics, 14.","DOI":"10.3390\/diagnostics14020136"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"De Luca, L., Mistrulli, R., Scirpa, R., Thiele, H., and De Luca, G. (2023). Contemporary Management of Cardiogenic Shock Complicating Acute Myocardial Infarction. J. Clin. Med., 12.","DOI":"10.3390\/jcm12062184"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1093\/ehjacc\/zuae047","article-title":"Efficacy and safety of mechanical circulatory support in acute myocardial infarction complicated by cardiogenic shock: DanGer trial in perspective","volume":"13","author":"Tavazzi","year":"2024","journal-title":"Eur. Heart J. Acute Cardiovasc. Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/S0735-1097(03)00084-6","article-title":"Left ventricular support by catheter-mounted axial flow pump reduces infarct size","volume":"41","author":"Meyns","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e004397","DOI":"10.1161\/CIRCHEARTFAILURE.117.004397","article-title":"Left Ventricular Mechanical Unloading by Total Support of Impella in Myocardial Infarction Reduces Infarct Size, Preserves Left Ventricular Function, and Prevents Subsequent Heart Failure in Dogs","volume":"11","author":"Saku","year":"2018","journal-title":"Circ.-Heart Fail."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1177\/1074248419869618","article-title":"Late Versus Early Myocardial Remodeling After Acute Myocardial Infarction: A Comparative Review on Mechanistic Insights and Clinical Implications","volume":"25","author":"Yalta","year":"2020","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1161\/01.CIR.0000096481.45105.13","article-title":"Atrophic remodeling of the heart in vivo simultaneously activates pathways of protein synthesis and degradation","volume":"108","author":"Razeghi","year":"2003","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"951","DOI":"10.4161\/auto.24273","article-title":"Autophagy: Regulation and role in development","volume":"9","author":"Hale","year":"2013","journal-title":"Autophagy"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.yjmcc.2015.12.003","article-title":"Autophagy during cardiac remodeling","volume":"95","author":"Nishida","year":"2016","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.healun.2017.02.012","article-title":"The ubiquitin-proteasome system: A potential therapeutic target for heart failure","volume":"36","author":"Barac","year":"2017","journal-title":"J. Heart Lung Transpl."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.yjmcc.2014.03.006","article-title":"MAFbx\/Atrogin-1 is required for atrophic remodeling of the unloaded heart","volume":"72","author":"Baskin","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e000016","DOI":"10.1161\/JAHA.113.000016","article-title":"Mechanical unloading activates FoxO3 to trigger Bnip3-dependent cardiomyocyte atrophy","volume":"2","author":"Cao","year":"2013","journal-title":"J. Am. Heart Assoc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"H2261","DOI":"10.1152\/ajpheart.01056.2010","article-title":"Autophagy limits acute myocardial infarction induced by permanent coronary artery occlusion, American journal of physiology","volume":"300","author":"Kanamori","year":"2011","journal-title":"Heart Circ. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1016\/j.jacc.2018.02.066","article-title":"Trehalose-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction","volume":"71","author":"Sciarretta","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.jacbts.2023.05.015","article-title":"Assessment of Autophagy Markers Suggests Increased Activity Following LVAD Therapy","volume":"8","author":"Martin","year":"2023","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S191","DOI":"10.1161\/CIRCULATIONAHA.108.842252","article-title":"Markers of autophagy are downregulated in failing human heart after mechanical unloading","volume":"120","author":"Kassiotis","year":"2009","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0022-5223(19)42744-X","article-title":"Improved technique of heart transplantation in rats","volume":"57","author":"Ono","year":"1969","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.healun.2013.10.006","article-title":"Dynamic patterns of ventricular remodeling and apoptosis in hearts unloaded by heterotopic transplantation","volume":"33","author":"Brinks","year":"2014","journal-title":"J. Heart Lung Transpl."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/j.jacc.2014.05.073","article-title":"Myocardial Atrophy and Chronic Mechanical Unloading of the Failing Human Heart","volume":"64","author":"Diakos","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.healun.2006.05.011","article-title":"Reverse remodeling of the myocardial extracellular matrix after prolonged left ventricular assist device support follows a biphasic pattern","volume":"25","author":"Bruggink","year":"2006","journal-title":"J. Heart Lung Transpl."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Schaefer, A., Schneeberger, Y., Schulz, S., Krasemann, S., Werner, T., Piasecki, A., H\u00f6ppner, G., M\u00fcller, C., Morhenn, K., and Lorenz, K. (2019). Analysis of fibrosis in control or pressure overloaded rat hearts after mechanical unloading by heterotopic heart transplantation. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-42263-1"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1093\/cvr\/cvs320","article-title":"Cardiac sympathetic neurons provide trophic signal to the heart via beta2-adrenoceptor-dependent regulation of proteolysis","volume":"97","author":"Zaglia","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1089\/neu.2017.5624","article-title":"Experimental Spinal Cord Injury Causes Left-Ventricular Atrophy and Is Associated with an Upregulation of Proteolytic Pathways","volume":"36","author":"Mansouri","year":"2019","journal-title":"J. Neurotrauma"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"280","DOI":"10.21037\/atm-22-592","article-title":"Changes in echocardiographic parameters of the donor\u2019s heart before and after heart transplantation and their relationship with post-transplant survival","volume":"10","author":"Zheng","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"H533","DOI":"10.1152\/ajpheart.00218.2013","article-title":"Preservation of left ventricular function and morphology in volume-loaded versus volume-unloaded heterotopic heart transplants","volume":"305","author":"Didie","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.1016\/j.jss.2012.01.053","article-title":"Heterotopic abdominal heart transplantation in rats for functional studies of ventricular unloading","volume":"179","author":"Ibrahim","year":"2013","journal-title":"J. Surg. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)","volume":"12","author":"Klionsky","year":"2016","journal-title":"Autophagy"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/9\/4422\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:28:09Z","timestamp":1760030889000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/9\/4422"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,6]]},"references-count":31,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ijms26094422"],"URL":"https:\/\/doi.org\/10.3390\/ijms26094422","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,6]]}}}