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Given the heart\u2019s exceptional mitochondrial density and energy dependence, mt\u2010tRFs serve as important signaling mediators within the mitochondria\u2013nucleus communication network, exhibiting significant potential in maintaining cardiovascular homeostasis and contributing to disease development. This review systematically examines mt\u2010tRF biogenesis, classification, and functional mechanisms, emphasizing their roles in cardiac development and vascular homeostasis. We analyze mt\u2010tRF involvement in major cardiovascular diseases, including mitochondrial cardiomyopathies, cardiac hypertrophy, heart failure, myocardial ischemia\u2013reperfusion injury, hypertension, and pulmonary arterial hypertension, highlighting disease\u2010specific expression profiles and functional consequences. The clinical potential of mt\u2010tRFs as emerging biomarkers and therapeutic targets presents promising opportunities for cardiovascular medicine. Through comprehensive analysis of their regulatory mechanisms and disease associations, this review provides insights into cardiovascular pathogenesis and supports the development of novel diagnostic and therapeutic strategies, positioning mt\u2010tRFs as valuable targets for precision cardiovascular medicine.<\/jats:p>","DOI":"10.1161\/jaha.125.044656","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T05:29:27Z","timestamp":1761888567000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Regulatory Roles of Mitochondrial tRNA\u2013Derived Fragments in Cardiovascular Health and Disease"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4133-4080","authenticated-orcid":false,"given":"Yang","family":"Zeng","sequence":"first","affiliation":[{"name":"The Affiliated Stomatological Hospital of Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi\u2010Lan","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1292-7236","authenticated-orcid":false,"given":"Jun","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11233"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000459"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3074"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303549"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00681.2024"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-014-0078-0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1837609"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2020.1732694"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2016.05.004"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2021.102118"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2024.14427"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.066126.118"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.02.053"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2016.203"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.02.035"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2017.1417631"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.246868"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00024.2007"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11216431"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom12030427"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.800171"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.729452"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-19-0789"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2019.03.012"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00136-14"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.06.022"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.51963"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1206761110"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.10.031"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.106114"},{"key":"e_1_3_2_32_2","first-page":"1656","article-title":"The biogenesis, mechanism and function of the tRNA\u2010derived small RNA (tsRNA): a review compared with microRNA","volume":"13","author":"Zhao Y","year":"2023","unstructured":"Zhao Y, Li X, Ye C, Huang C, Lv X, Li J. 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