Targeting Inflammation by Pioglitazone and its R-Enantiomer Mitigates Pathological Myocardial Remodeling in Murine Hypertrophic Cardiomyopathy
Year: 2026
Type: article
Abstract: 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.
Authors: Anna-Theresa Pfaller, Claudia Veneziano, Sarala Raj Murthi, Jan B. Stöckl, Bachuki Shashikadze, Florian Flenkenthaler, Josh Gorham, Alessandra Moretti, Ana Kitanovic, Linden J. Gearing, Frederik Heinrich, Pawel Durek, Katrin Lehmann, Mir-Farzin Mashreghi, Peter Ewert, Thomas Fröhlich, Joachim P. Schmitt, Nadine Spielmann, Martin Hrabě de Angelis, Manuel Schmid, Christopher N. Toepfer, Eicke Latz, Karin Klingel, Gianluca Santamaria, Jonathan G. Seidman, Christine E. Seidman, Cordula M. Wolf
Institutions: German Centre for Cardiovascular Research, Deutsches Herzzentrum München, Technical University of Munich, Magna Graecia University, Ludwig-Maximilians-Universität München, Harvard University, TUM Klinikum, German Rheumatism Research Centre, Zuse Institute Berlin, Düsseldorf University Hospital, Heinrich Heine University Düsseldorf, Helmholtz Munich, Centre for Human Genetics, University of Oxford, Universitätsklinikum Tübingen
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,750
OpenAlex ID: W7164477450