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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)
Publ. Version/Full Text 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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Publication type Article: Journal article
Document type Scientific Article
Keywords Hypertrophic Cardiomyopathy ; Inflammation And Oxidative Stress ; Mitochondrial Dysfunction ; Myocardial Hypertrophy And Fibrosis ; Pioglitazone
ISSN (print) / ISBN 2452-302X
e-ISSN 2452-302X
Journal JACC: Basic to Translational Science
Quellenangaben Volume: 11, Issue: 7, Pages: , Article Number: 101574 Supplement: ,
Publisher Elsevier
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)