{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:53:56Z","timestamp":1787018036929,"version":"build-2736575974"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>\n                      Pulmonary hypertension is a severe disease with high mortality rates due to right ventricular (RV) failure. The molecular and cellular processes involved in RV remodeling, including Ca\n                      <jats:sup>2+<\/jats:sup>\n                      handling, remain elusive due to the lack of relevant animal models. In this study, we aim to understand better the pathophysiological mechanisms involved in RV failure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We used the chronic thromboembolic pulmonary hypertension (CTEPH) pig model, which leads to progressive RV hypertrophy and dysfunction. Cellular, molecular unbiased global transcriptional profiling and biochemical analyses were performed on RV cardiomyocytes from CTEPH and Sham-operated pigs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      CTEPH pigs replicated the hemodynamics and histological changes of human CTEPH features. Transcriptome analysis in Sham and CTEPH pigs revealed molecular RV remodeling close to human patients with pulmonary arterial hypertension with decompensated RV function and notably identified changes in genes involved in Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signaling. At the cellular level, CTEPH myocytes presented reduced L-type Ca\n                      <jats:sup>2+<\/jats:sup>\n                      current in association with reduced mRNA of\n                      <jats:italic toggle=\"yes\">CACNA1C<\/jats:italic>\n                      . Furthermore, CTEPH myocytes showed lower [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      transients, decreased sarcoplasmic reticulum Ca\n                      <jats:sup>2+<\/jats:sup>\n                      content, and decreased cell shortening, related to reduced SERCA2a (Sarco\/endoplasmic reticulum Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -ATPase isoform 2a) protein expression. Moreover, CTEPH cardiomyocytes exhibited reduced Ca\n                      <jats:sup>2+<\/jats:sup>\n                      spark occurrence, which relied on smaller RyR2 (ryanodine receptor 2) clusters and T-tubule disorganization. Finally, these alterations in Ca\n                      <jats:sup>2+<\/jats:sup>\n                      homeostasis were also associated with an increased store-operated Ca\n                      <jats:sup>2+<\/jats:sup>\n                      entry and the de novo expression of the Ca\n                      <jats:sup>2+<\/jats:sup>\n                      sensor protein STIM1L (stromal interaction molecule 1 long isoform) in CTEPH myocytes as well as in RV from human patients with pulmonary arterial hypertension.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      Our data reveal cellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      cycling remodeling that participates in the pathogenesis of RV dysfunction and may constitute therapeutic targets to limit the development of RV dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.124.012293","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T05:00:16Z","timestamp":1744952416000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Ca\n                    <sup>2+<\/sup>\n                    Cycling Alteration in a Porcine Model of Right Ventricular Dysfunction"],"prefix":"10.1161","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9515-6571","authenticated-orcid":true,"given":"Fabrice","family":"Antigny","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, UMR-S 999, Hypertension Pulmonaire: Physiopathologie and Innovation Th\u00e9rapeutique (HPPIT), AP-HP, H\u00f4pital Bic\u00eatre, H\u00f4pital Marie Lannelongue (Groupe Hospitalier Paris Saint Joseph), ERN-LUNG, Le Plessis Robinson, France (F.A., B.M., G.F., G.R., A.S.-M.W., A.A., J. Grynblat, X.J., J.L.P., S.D.V., D.B., A.B., J. Guihaire, D.M., M.H., O.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3322-5355","authenticated-orcid":true,"given":"Rui","family":"Luo","sequence":"additional","affiliation":[{"name":"Inserm, UMR-S 1180, Signalisation et Physiopathologie Cardiovasculaire, Universit\u00e9 Paris-Saclay, Orsay, France (R.L., R.P., F.L., G.G., A.-M.G., J.-P.B., J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2229-4700","authenticated-orcid":true,"given":"Romain","family":"Perrier","sequence":"additional","affiliation":[{"name":"Inserm, UMR-S 1180, Signalisation et Physiopathologie Cardiovasculaire, Universit\u00e9 Paris-Saclay, Orsay, France (R.L., R.P., F.L., G.G., A.-M.G., J.-P.B., J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2364-5269","authenticated-orcid":true,"given":"Bastien","family":"Masson","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, UMR-S 999, Hypertension Pulmonaire: Physiopathologie and Innovation Th\u00e9rapeutique (HPPIT), AP-HP, H\u00f4pital Bic\u00eatre, H\u00f4pital Marie Lannelongue (Groupe Hospitalier Paris Saint Joseph), ERN-LUNG, Le Plessis Robinson, France (F.A., B.M., G.F., G.R., A.S.-M.W., A.A., J. Grynblat, X.J., J.L.P., S.D.V., D.B., A.B., J. Guihaire, D.M., M.H., O.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4986-7258","authenticated-orcid":true,"given":"Guillaume","family":"Fadel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, UMR-S 999, Hypertension Pulmonaire: Physiopathologie and Innovation Th\u00e9rapeutique (HPPIT), AP-HP, H\u00f4pital Bic\u00eatre, H\u00f4pital Marie Lannelongue (Groupe Hospitalier Paris Saint Joseph), ERN-LUNG, Le Plessis Robinson, France (F.A., B.M., G.F., G.R., A.S.-M.W., A.A., J. Grynblat, X.J., J.L.P., S.D.V., D.B., A.B., J. Guihaire, D.M., M.H., O.M.)."},{"name":"Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardio-Pulmonaire, H\u00f4pital Marie Lannelongue, Le Plessis Robinson, France (G.F., O.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6419-4332","authenticated-orcid":true,"given":"Gr\u00e9goire","family":"Ruffenach","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, UMR-S 999, Hypertension Pulmonaire: Physiopathologie and Innovation Th\u00e9rapeutique (HPPIT), AP-HP, H\u00f4pital Bic\u00eatre, H\u00f4pital Marie Lannelongue (Groupe Hospitalier Paris Saint Joseph), ERN-LUNG, Le Plessis Robinson, France (F.A., B.M., G.F., G.R., A.S.-M.W., A.A., J. Grynblat, X.J., J.L.P., S.D.V., D.B., A.B., J. Guihaire, D.M., M.H., O.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2078-3271","authenticated-orcid":true,"given":"Ana\u00efs","family":"Saint-Martin Willer","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, UMR-S 999, Hypertension Pulmonaire: Physiopathologie and Innovation Th\u00e9rapeutique (HPPIT), AP-HP, H\u00f4pital Bic\u00eatre, H\u00f4pital Marie Lannelongue (Groupe Hospitalier Paris Saint Joseph), ERN-LUNG, Le Plessis Robinson, France (F.A., B.M., G.F., G.R., A.S.-M.W., A.A., J. Grynblat, X.J., J.L.P., S.D.V., D.B., A.B., J. Guihaire, D.M., M.H., O.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2709-1486","authenticated-orcid":true,"given":"Ali","family":"Akamkam","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, UMR-S 999, Hypertension Pulmonaire: Physiopathologie and Innovation Th\u00e9rapeutique (HPPIT), AP-HP, H\u00f4pital Bic\u00eatre, H\u00f4pital Marie Lannelongue (Groupe Hospitalier Paris Saint Joseph), ERN-LUNG, Le Plessis Robinson, France (F.A., B.M., G.F., G.R., A.S.-M.W., A.A., J. Grynblat, X.J., J.L.P., S.D.V., D.B., A.B., J. Guihaire, D.M., M.H., O.M.)."},{"name":"Service de Chirurgie Cardiaque et Vasculaire, H\u00f4pital Marie Lannelongue, Le Plessis Robinson, France (A.A., S.D.V., D.B., J. Guihaire)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5593-3383","authenticated-orcid":true,"given":"Julien","family":"Grynblat","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, UMR-S 999, Hypertension Pulmonaire: Physiopathologie and Innovation Th\u00e9rapeutique (HPPIT), AP-HP, H\u00f4pital Bic\u00eatre, H\u00f4pital Marie Lannelongue (Groupe Hospitalier Paris Saint Joseph), ERN-LUNG, Le Plessis Robinson, France (F.A., B.M., G.F., G.R., A.S.-M.W., A.A., J. Grynblat, X.J., J.L.P., S.D.V., D.B., A.B., J. Guihaire, D.M., M.H., O.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Ja\u00efs","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, UMR-S 999, Hypertension Pulmonaire: Physiopathologie and Innovation Th\u00e9rapeutique (HPPIT), AP-HP, H\u00f4pital Bic\u00eatre, H\u00f4pital Marie Lannelongue (Groupe Hospitalier Paris Saint Joseph), ERN-LUNG, Le Plessis Robinson, France (F.A., B.M., G.F., G.R., A.S.-M.W., A.A., J. Grynblat, X.J., J.L.P., S.D.V., D.B., A.B., J. Guihaire, D.M., M.H., O.M.)."},{"name":"Service de Pneumologie et Soins Intensifs Respiratoires, Centre de R\u00e9f\u00e9rence de l\u2019Hypertension Pulmonaire, Le Kremlin-Bic\u00eatre, France (X.J., D.M., M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4426-9645","authenticated-orcid":true,"given":"Jer\u00f4me","family":"Le Pavec","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, UMR-S 999, Hypertension Pulmonaire: Physiopathologie and Innovation Th\u00e9rapeutique (HPPIT), AP-HP, H\u00f4pital Bic\u00eatre, H\u00f4pital Marie Lannelongue (Groupe Hospitalier Paris Saint Joseph), ERN-LUNG, Le Plessis Robinson, France (F.A., B.M., G.F., G.R., A.S.-M.W., A.A., J. Grynblat, X.J., J.L.P., S.D.V., D.B., A.B., J. Guihaire, D.M., M.H., O.M.)."},{"name":"Service de Pneumologie et Transplantation Pulmonaire, H\u00f4pital Marie Lannelongue, Le Plessis Robinson, France (J.L.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3065-9247","authenticated-orcid":true,"given":"Simon","family":"Dang Van","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, UMR-S 999, Hypertension Pulmonaire: Physiopathologie and Innovation Th\u00e9rapeutique (HPPIT), AP-HP, H\u00f4pital Bic\u00eatre, H\u00f4pital Marie Lannelongue (Groupe Hospitalier Paris Saint Joseph), ERN-LUNG, Le Plessis Robinson, France (F.A., B.M., G.F., G.R., A.S.-M.W., A.A., J. Grynblat, X.J., J.L.P., S.D.V., D.B., A.B., J. Guihaire, D.M., M.H., O.M.)."},{"name":"Service de Chirurgie Cardiaque et Vasculaire, H\u00f4pital Marie Lannelongue, Le Plessis Robinson, France (A.A., S.D.V., D.B., J. Guihaire)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doroth\u00e9e","family":"Brunet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, UMR-S 999, Hypertension Pulmonaire: Physiopathologie and Innovation Th\u00e9rapeutique (HPPIT), AP-HP, H\u00f4pital Bic\u00eatre, H\u00f4pital Marie Lannelongue (Groupe Hospitalier Paris Saint Joseph), ERN-LUNG, Le Plessis Robinson, France (F.A., B.M., G.F., G.R., A.S.-M.W., A.A., J. Grynblat, X.J., J.L.P., S.D.V., D.B., A.B., J. Guihaire, D.M., M.H., O.M.)."},{"name":"Service de Chirurgie Cardiaque et Vasculaire, H\u00f4pital Marie Lannelongue, Le Plessis Robinson, France (A.A., S.D.V., D.B., J. Guihaire)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Lefebvre","sequence":"additional","affiliation":[{"name":"Inserm, UMR-S 1180, Signalisation et Physiopathologie Cardiovasculaire, Universit\u00e9 Paris-Saclay, Orsay, France (R.L., R.P., F.L., G.G., A.-M.G., J.-P.B., J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9873-860X","authenticated-orcid":true,"given":"Garance","family":"G\u00e9rard","sequence":"additional","affiliation":[{"name":"Inserm, UMR-S 1180, Signalisation et Physiopathologie Cardiovasculaire, Universit\u00e9 Paris-Saclay, Orsay, France (R.L., R.P., F.L., G.G., A.-M.G., J.-P.B., J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5997-2694","authenticated-orcid":true,"given":"S\u00e9verine","family":"Domenichini","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, CNRS, Ing\u00e9nierie et Plateformes au Service de l\u2019Innovation Th\u00e9rapeutique-Plateforme MIPSIT, Orsay, France (S.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1510-3347","authenticated-orcid":true,"given":"Ang\u00e8le","family":"Bo\u00ebt","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, UMR-S 999, Hypertension Pulmonaire: Physiopathologie and Innovation Th\u00e9rapeutique (HPPIT), AP-HP, H\u00f4pital Bic\u00eatre, H\u00f4pital Marie Lannelongue (Groupe Hospitalier Paris Saint Joseph), ERN-LUNG, Le Plessis Robinson, France (F.A., B.M., G.F., G.R., A.S.-M.W., A.A., J. Grynblat, X.J., J.L.P., S.D.V., D.B., A.B., J. Guihaire, D.M., M.H., O.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7414-3176","authenticated-orcid":true,"given":"Julien","family":"Guihaire","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, UMR-S 999, Hypertension Pulmonaire: Physiopathologie and Innovation Th\u00e9rapeutique (HPPIT), AP-HP, H\u00f4pital Bic\u00eatre, H\u00f4pital Marie Lannelongue (Groupe Hospitalier Paris Saint Joseph), ERN-LUNG, Le Plessis Robinson, France (F.A., B.M., G.F., G.R., A.S.-M.W., A.A., J. Grynblat, X.J., J.L.P., S.D.V., D.B., A.B., J. Guihaire, D.M., M.H., O.M.)."},{"name":"Service de Chirurgie Cardiaque et Vasculaire, H\u00f4pital Marie Lannelongue, Le Plessis Robinson, France (A.A., S.D.V., D.B., J. Guihaire)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0009-2884","authenticated-orcid":true,"given":"Ana-Maria","family":"Gomez","sequence":"additional","affiliation":[{"name":"Inserm, UMR-S 1180, Signalisation et Physiopathologie Cardiovasculaire, Universit\u00e9 Paris-Saclay, Orsay, France (R.L., R.P., F.L., G.G., A.-M.G., J.-P.B., J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-6922","authenticated-orcid":true,"given":"David","family":"Montani","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Inserm, UMR-S 999, Hypertension Pulmonaire: Physiopathologie and Innovation Th\u00e9rapeutique (HPPIT), AP-HP, H\u00f4pital Bic\u00eatre, H\u00f4pital Marie Lannelongue (Groupe Hospitalier Paris Saint Joseph), ERN-LUNG, Le Plessis Robinson, France (F.A., B.M., G.F., G.R., A.S.-M.W., A.A., J. Grynblat, X.J., J.L.P., S.D.V., D.B., A.B., J. 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