{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T05:00:51Z","timestamp":1768885251923,"version":"3.49.0"},"reference-count":40,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,10]],"date-time":"2020-10-10T00:00:00Z","timestamp":1602288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["18IPA34170062"],"award-info":[{"award-number":["18IPA34170062"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K01HL121045, F32HL137394, K23HL123938, R01HL138519,R01HL133290, K12HD087023, R01HL119234"],"award-info":[{"award-number":["K01HL121045, F32HL137394, K23HL123938, R01HL138519,R01HL133290, K12HD087023, R01HL119234"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-16-1-0622"],"award-info":[{"award-number":["W81XWH-16-1-0622"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brain-derived neurotrophic factor (BDNF) is a neuronal growth and survival factor that harbors cardioprotective qualities that may attenuate dilated cardiomyopathy. In ~30% of the population, BDNF has a common, nonsynonymous single nucleotide polymorphism rs6265 (Val66Met), which might be correlated with increased risk of cardiovascular events. We previously showed that BDNF correlates with better cardiac function in Duchenne muscular dystrophy (DMD) patients. However, the effect of the Val66Met polymorphism on cardiac function has not been determined. The goal of the current study was to determine the effects of rs6265 on BDNF biomarker suitability and DMD cardiac functions more generally. We assessed cardiovascular and skeletal muscle function in human DMD patients segregated by polymorphic allele. We also compared echocardiographic, electrophysiologic, and cardiomyocyte contractility in C57\/BL-6 wild-type mice with rs6265 polymorphism and in mdx\/mTR (mDMD) mouse model of DMD. In human DMD patients, plasma BDNF levels had a positive correlation with left ventricular function, opposite to that seen in rs6265 carriers. There was also a substantial decrease in skeletal muscle function in carriers compared to the Val homozygotes. Surprisingly, the opposite was true when cardiac function of DMD carriers and non-carriers were compared. On the other hand, Val66Met wild-type mice had only subtle functional differences at baseline but significantly decreased cardiomyocyte contractility. Our results indicate that the Val66Met polymorphism alters myocyte contractility, conferring worse skeletal muscle function but better cardiac function in DMD patients. Moreover, these results suggest a mechanism for the relative preservation of cardiac tissues compared to skeletal muscle in DMD patients and underscores the complexity of BDNF signaling in response to mechanical workload.<\/jats:p>","DOI":"10.3390\/ijms21207466","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T21:48:38Z","timestamp":1602625718000},"page":"7466","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The BDNF rs6265 Polymorphism is a Modifier of Cardiomyocyte Contractility and Dilated Cardiomyopathy"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3464-6569","authenticated-orcid":false,"suffix":"Jr.","given":"Frank J.","family":"Raucci","sequence":"first","affiliation":[{"name":"Thomas P. Graham Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Division of Pediatric Cardiology, Department of Pediatrics, Children\u2019s Hospital of Richmond at Virginia Commonwealth University, Richmond, VA 23219, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9409-1366","authenticated-orcid":false,"given":"Anand Prakash","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Disease, Department of Medicine, University of Alabama Birmingham School of Medicine, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Soslow","sequence":"additional","affiliation":[{"name":"Thomas P. Graham Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry W.","family":"Markham","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Pediatrics, Riley Hospital for Children at Indiana University Health, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Zhong","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7244-241X","authenticated-orcid":false,"given":"Wejdan","family":"Aljafar","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasja","family":"Lessiohadi","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassandra P.","family":"Awgulewitsch","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7989-577X","authenticated-orcid":false,"given":"Prachi","family":"Umbarkar","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Disease, Department of Medicine, University of Alabama Birmingham School of Medicine, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinkun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Disease, Department of Medicine, University of Alabama Birmingham School of Medicine, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Presley L.","family":"Cannon","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0566-1743","authenticated-orcid":false,"given":"Maciej","family":"Buchowski","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph T.","family":"Roland","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica J.","family":"Carrier","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William B.","family":"Burnette","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonis K.","family":"Hatzopoulos","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hind","family":"Lal","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Disease, Department of Medicine, University of Alabama Birmingham School of Medicine, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristi L.","family":"Galindo","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Department of Biology, Western Kentucky University, Bowling Green, KY 42101, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.pharmthera.2013.01.004","article-title":"GDNF, NGF and BDNF as therapeutic options for neurodegeneration","volume":"138","author":"Allen","year":"2013","journal-title":"Pharmacol. 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