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Pfaller, A.T.* ; Veneziano, C.* ; Murthi, S.R.* ; Stöckl, J.B.* ; Shashikadze, B.* ; Flenkenthaler, F.* ; Gorham, J.* ; Moretti, A.* ; Kitanovic, A.* ; Gearing, L.J.* ; Heinrich, F.* ; Durek, P.* ; Lehmann, K.* ; Mashreghi, M.F.* ; Ewert, P.* ; Fröhlich, T.* ; Schmitt, J.P.* ; Spielmann, N. ; Hrabě de Angelis, M. ; Schmid, M.* ; Toepfer, C.N.* ; Latz, E.* ; Klingel, K.* ; Santamaria, G.* ; Seidman, J.G.* ; Seidman, C.E.* ; Wolf, C.M.*

Targeting inflammation by pioglitazone and its R-enantiomer mitigates pathological myocardial remodeling in murine hypertrophic cardiomyopathy.

JACC-Basic Transl. Sci. 11:101574 (2026)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Hypertrophic cardiomyopathy (HCM) is driven by sarcomeric mutations that cause energetic failure and secondary inflammation. This study demonstrates that targeting this metabolic-inflammatory axis with pioglitazone or its peroxisome proliferator-activated receptor gamma inactive enantiomer, R-pioglitazone, reverses disease progression in a murine HCM model. Both agents restored mitochondrial function (including Mitochondrial Pyruvate Carrier 1 [MPC1] levels) and resolved inflammation. Notably, R-pioglitazone showed superior efficacy, reducing interstitial fibrosis by >95% and hypertrophy by 33% without affecting healthy control hearts. These findings identify R-pioglitazone as a promising, mechanism-based candidate for disease-modifying therapy in HCM.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Hypertrophic Cardiomyopathy ; Inflammation And Oxidative Stress ; Mitochondrial Dysfunction ; Myocardial Hypertrophy And Fibrosis ; Pioglitazone; Metabolism; Prevention; Energetics; Mutations; Insights; Disease; Events; Hcm
ISSN (print) / ISBN 2452-302X
e-ISSN 2452-302X
Zeitschrift JACC: Basic to Translational Science
Quellenangaben Band: 11, Heft: 7, Seiten: , Artikelnummer: 101574 Supplement: ,
Verlag Elsevier
Verlagsort 101 Park Avenue, 24th Floor, New York, Ny, United States
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
Förderungen Principal investigator of the Transregio Research Units by German Research Foundation
European Research Council (ERCAd)
German Research Foundation-Transregio Research Units
European Research Council-ERCAd
Stiftung Kinderherz
Else-Kroener Fresenius Stiftung and Foerderverein des Deutschen Herzzentrums