{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T18:29:44Z","timestamp":1787077784984,"version":"build-2736575974"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Exercise intolerance, promoted by skeletal muscle- and mitochondrial dysfunction, has been identified as a therapeutic target in heart failure with preserved ejection fraction (HFpEF). In the context of mitochondrial dysfunction, altered cardiolipin integrity has been reported in the myocardium of HFpEF, suggesting Elamipretide, a cardiolipin stabilizing agent, as potential therapeutic approach. The present study investigated cardiolipin dysregulation in the skeletal muscle of HFpEF rats and analyzed the effect of Elamipretide treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Female zucker fatty spontaneously hypertensive heart failure F1 hybrid lean (n=10, control) and obese rats (n=24, HFpEF) were included. At 20 weeks of age, HFpEF rats were randomized into 2 groups receiving NaCl (n=12) or Elamipretide (n=12) for 12 weeks. Skeletal muscle tissue was collected for whole-muscle force, single-fiber mechanics, mitochondrial respiration, histology and molecular analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      HFpEF rats exhibited reduced cardiolipin levels (\u22126.8%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.007) and maturation (shown via tafazzin expression), contractile dysfunction, titin hyperphosphorylation, fiber atrophy and increased oxidative stress markers. Elamipretide improved whole muscle (soleus: +8.2%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.041, extensor digitorum longus: +10.9%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.016) and single-fiber (soleus: +173.2%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001, extensor digitorum longus: +66.0%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =ns) contractile function and titin phosphorylation (soleus: \u221235.4%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001, extensor digitorum longus: \u221240.2%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001), while preventing atrophy development (soleus: +49%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.001, extensor digitorum longus: +54.8%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001). Improved mitochondrial function, presumably through cardiolipin-mediated improvements in oxidative phosphorylation, could be associated with muscle force and cardiolipin integrity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Our data highlight cardiolipin stabilization as a key modulator of mitochondrial and contractile function in HFpEF, identifying Elamipretide as a promising therapeutic approach for skeletal muscle dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.126.014397","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T09:00:22Z","timestamp":1781514022000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting Mitochondrial Dysfunction With Elamipretide (SS-31) Improves Skeletal Muscle Performance in a HFpEF Rat Model"],"prefix":"10.1161","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8110-1943","authenticated-orcid":true,"given":"Beatrice","family":"Vahle","sequence":"first","affiliation":[{"name":"Heart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, Germany (B.V., A.S., A.A., A.M., P.B., J.F., A.L., V.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0695-3502","authenticated-orcid":true,"given":"Sven","family":"Weidner","sequence":"additional","affiliation":[{"name":"Motion and Exercise Science, University of Stuttgart, Germany (S.W., A.T., T.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6957-5094","authenticated-orcid":true,"given":"Andr\u00e9","family":"Tomalka","sequence":"additional","affiliation":[{"name":"Motion and Exercise Science, University of Stuttgart, Germany (S.W., A.T., T.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0003-6882","authenticated-orcid":true,"given":"Antje","family":"Schauer","sequence":"additional","affiliation":[{"name":"Heart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, Germany (B.V., A.S., A.A., A.M., P.B., J.F., A.L., V.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2770-5366","authenticated-orcid":true,"given":"Antje","family":"Augstein","sequence":"additional","affiliation":[{"name":"Heart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, Germany (B.V., A.S., A.A., A.M., P.B., J.F., A.L., V.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"M\u00e4nnel","sequence":"additional","affiliation":[{"name":"Heart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, Germany (B.V., A.S., A.A., A.M., P.B., J.F., A.L., V.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Barthel","sequence":"additional","affiliation":[{"name":"Heart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, Germany (B.V., A.S., A.A., A.M., P.B., J.F., A.L., V.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Heart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, Germany (B.V., A.S., A.A., A.M., P.B., J.F., A.L., V.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6722-9370","authenticated-orcid":true,"given":"Grietje","family":"Beck","sequence":"additional","affiliation":[{"name":"Integrative Pathophysiology, Department for Anesthesiology and Intensive Operative Care, Medical Faculty Mannheim, University of Heidelberg, Germany (G.B., S.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9009-210X","authenticated-orcid":true,"given":"Siegfried","family":"Labeit","sequence":"additional","affiliation":[{"name":"Integrative Pathophysiology, Department for Anesthesiology and Intensive Operative Care, Medical Faculty Mannheim, University of Heidelberg, Germany (G.B., S.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1740-2474","authenticated-orcid":true,"given":"T. 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