{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:41:02Z","timestamp":1792726862707,"version":"4.5.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2014,12,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Despite the accumulating genetic and molecular investigations into hypertrophic cardiomyopathy (HCM), it remains unclear how this condition develops and worsens pathologically and clinically in terms of the genetic\u2013environmental interactions. Establishing a human disease model for HCM would help to elucidate these disease mechanisms; however, cardiomyocytes from patients are not easily obtained for basic research. Patient\u2010specific induced pluripotent stem cells (\n                      <jats:styled-content style=\"fixed-case\">iPSCs<\/jats:styled-content>\n                      ) potentially hold much promise for deciphering the pathogenesis of HCM. The purpose of this study is to elucidate the interactions between genetic backgrounds and environmental factors involved in the disease progression of HCM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      We generated\n                      <jats:styled-content style=\"fixed-case\">iPSC<\/jats:styled-content>\n                      s from 3 patients with HCM and 3 healthy control subjects, and cardiomyocytes were differentiated. The HCM pathological phenotypes were characterized based on morphological properties and high\u2010speed video imaging. The differences between control and HCM\n                      <jats:styled-content style=\"fixed-case\">iPSC<\/jats:styled-content>\n                      \u2010derived cardiomyocytes were mild under baseline conditions in pathological features. To identify candidate disease\u2010promoting environmental factors, the cardiomyocytes were stimulated by several cardiomyocyte hypertrophy\u2010promoting factors. Interestingly, endothelin\u20101 strongly induced pathological phenotypes such as cardiomyocyte hypertrophy and intracellular myofibrillar disarray in the HCM\n                      <jats:styled-content style=\"fixed-case\">iPSC<\/jats:styled-content>\n                      \u2010derived cardiomyocytes. We then reproduced these phenotypes in neonatal cardiomyocytes from the heterozygous\n                      <jats:italic>Mybpc3<\/jats:italic>\n                      \u2010targeted knock in mice. High\u2010speed video imaging with motion vector prediction depicted physiological contractile dynamics in the\n                      <jats:styled-content style=\"fixed-case\">iPSC<\/jats:styled-content>\n                      \u2010derived cardiomyocytes, which revealed that self\u2010beating HCM\n                      <jats:styled-content style=\"fixed-case\">iPSC<\/jats:styled-content>\n                      \u2010derived single cardiomyocytes stimulated by endothelin\u20101 showed variable contractile directions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Interactions between the patient's genetic backgrounds and the environmental factor endothelin\u20101 promote the HCM pathological phenotype and contractile variability in the HCM\n                      <jats:styled-content style=\"fixed-case\">iPSC<\/jats:styled-content>\n                      \u2010derived cardiomyocytes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.114.001263","type":"journal-article","created":{"date-parts":[[2014,11,12]],"date-time":"2014-11-12T00:06:33Z","timestamp":1415750793000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":134,"title":["Endothelin\u20101 Induces Myofibrillar Disarray and Contractile Vector Variability in Hypertrophic Cardiomyopathy\u2013Induced Pluripotent Stem Cell\u2013Derived Cardiomyocytes"],"prefix":"10.1161","volume":"3","author":[{"given":"Atsushi","family":"Tanaka","sequence":"first","affiliation":[{"name":"Department of Cardiology, Keio University School of Medicine, Tokyo, Japan"},{"name":"Department of Cardiovascular Medicine, Saga University, Saga, 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