{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:11:26Z","timestamp":1790208686590,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key R&amp;D Program of China","award":["2021YFC2500500"],"award-info":[{"award-number":["2021YFC2500500"]}]},{"name":"National Key R&amp;D Program of China","award":["82100395"],"award-info":[{"award-number":["82100395"]}]},{"name":"National Key R&amp;D Program of China","award":["82100276"],"award-info":[{"award-number":["82100276"]}]},{"name":"National Natural Science Foundation of China","award":["2021YFC2500500"],"award-info":[{"award-number":["2021YFC2500500"]}]},{"name":"National Natural Science Foundation of China","award":["82100395"],"award-info":[{"award-number":["82100395"]}]},{"name":"National Natural Science Foundation of China","award":["82100276"],"award-info":[{"award-number":["82100276"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Critical limb ischemia (CLI) is a common complication of diabetes mellitus that typically occurs in the later stages of the disease. Vascularization is indeed an important physiological process involving the formation of new blood vessels from existing ones. It occurs in response to various normal and pathophysiological conditions, and one of its critical roles is to compensate for inadequate oxygen supply, which is often seen in situations like chronic limb ischemia (CLI). Histidine triad nucleotide-binding protein 1 (Hint1) is a member of the Hint family that has been shown to attenuate cardiac hypertrophy, but its role in vascularization still needs to be clarified. In this study, we investigated the role of Hint1 in CLI. We found that Hint1 is significantly reduced in the muscle tissue of STZ-induced diabetic mice and high-glucose (HG)-treated endothelial cells (ECs). Hint1 deletion impaired blood flow recovery and vascularization, whereas Hint1 overexpression promoted these processes. In addition, our in vitro study showed that Hint1 deficiency aggravated mitochondrial dysfunction in ECs, as evidenced by impaired mitochondrial respiration, decreased mitochondrial membrane potential, and increased reactive oxygen species. Our findings suggest that Hint1 deficiency impairs blood perfusion by damaging mitochondrial function and that Hint1 may represent a potential therapeutic target for treating CLI.<\/jats:p>","DOI":"10.3390\/nu15234859","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T12:12:13Z","timestamp":1700568733000},"page":"4859","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Histidine Triad Nucleotide-Binding Protein 1 Improves Critical Limb Ischemia by Regulating Mitochondrial Homeostasis"],"prefix":"10.3390","volume":"15","author":[{"given":"Tingwen","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai 200032, China"},{"name":"Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai 200032, China"},{"name":"Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai 200032, China"},{"name":"National Clinical Research Center for Interventional Medicine, Shanghai 200032, China"},{"name":"Department of Cardiology, Rizhao International Heart Hospital, Rizhao 276825, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9897-3577","authenticated-orcid":false,"given":"Shuo","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai 200032, China"},{"name":"Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai 200032, China"},{"name":"Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai 200032, China"},{"name":"National Clinical Research Center for Interventional Medicine, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai 200032, China"},{"name":"Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai 200032, China"},{"name":"Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai 200032, China"},{"name":"National Clinical Research Center for Interventional Medicine, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7620-0813","authenticated-orcid":false,"given":"Xinyu","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai 200032, China"},{"name":"Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai 200032, China"},{"name":"Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai 200032, China"},{"name":"National Clinical Research Center for Interventional Medicine, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbo","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai 200032, China"},{"name":"Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai 200032, China"},{"name":"Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai 200032, China"},{"name":"National Clinical Research Center for Interventional Medicine, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0968-0004(97)01074-8","article-title":"Molecular mechanisms of blood vessel formation","volume":"22","author":"Bussolino","year":"1997","journal-title":"Trends Biochem. 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