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Stromal cell\u2013derived factor\u20141 is released during acute cardiac injury and heart failure, but it has a short half-life because of degradation by dipeptidyl peptidase\u20134. Inhibition of dipeptidyl peptidase\u20134 potentiates the actions of stromal cell\u2013derived factor\u20141 and, theoretically, could enhance cardiac recovery. However, in large-scale trials in patients with type 2 diabetes mellitus, dipeptidyl peptidase\u20134 inhibitors have not reduced the risk of atherosclerotic ischemic events, and they have unexpectedly increased the risk of heart failure, most probably heart failure with a preserved ejection fraction. Such an outcome might be explained if the channeling of mesenchymal stem cells to the heart by the actions of stromal cell\u2013derived factor\u20141 (especially from nearby adipose tissue) were followed by the transformation of these cells into fibroblasts rather than cardiomyocytes. This concern has been supported by experimental studies; the resulting fibrosis would be expected to exacerbate the pathophysiological derangements that lead to heart failure with a preserved ejection fraction. Given the widespread use of dipeptidyl peptidase\u20134 inhibitors, the possibility that these drugs potentiate the cardiac homing of mesenchymal stem cells that cause myocardial fibrosis (rather than repair) warrants further study.<\/jats:p>","DOI":"10.1161\/circulationaha.117.032190","type":"journal-article","created":{"date-parts":[[2018,5,7]],"date-time":"2018-05-07T18:10:32Z","timestamp":1525716632000},"page":"2068-2073","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["The Alchemist\u2019s Nightmare"],"prefix":"10.1161","volume":"137","author":[{"given":"Milton","family":"Packer","sequence":"first","affiliation":[{"name":"Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.11.016"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0695-y"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3791\/55757"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311827"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv136"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2013.07.016"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1517\/14712590903460286"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1600"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01134.2008"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.117.004106"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000147780.30124.CF"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.01.024"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309281"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00059-014-4169-z"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0141408"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303579"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.12.1136"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv254"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.300440"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2016.07.009"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.000343"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.12.026"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00142-5"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00735.2015"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1501352"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1307684"},{"key":"e_1_3_2_28_2","unstructured":"US Food and Drug Administration. 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