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JACC: Basic to Translational Science

Targeting Inflammation by Pioglitazone and its R-Enantiomer Mitigates Pathological Myocardial Remodeling in Murine Hypertrophic Cardiomyopathy

  • June 13, 2026
  • Cordula Wolf, et al., Technical University of Munich
Product:
Mouse Panel 120
Topic:
Inflammation
Disease Area:
Hypertrophic Cardiomyopathy
Sample Type:
Plasma-Mouse
Back to Publications​
  • June 13, 2026
  • Cordula Wolf, et al., Technical University of Munich
Topic/Product:
Mouse Panel 120
Disease Area:
Hypertrophic Cardiomyopathy
Sample Type:
Plasma-Mouse

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.

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Authors & Affiliations

Anna-Theresa Pfaller, BEngᵃ˒ᵇ*, Claudia Veneziano, PhDᶜ*, Sarala Raj Murthi, PhDᵃ, Jan B. Stöckl, PhDᵈ, Bachuki Shashikadze, PhDᵈ, Florian Flenkenthaler, PhDᵈ, Josh Gorham, BAᵉ, Alessandra Moretti, PhDᵇ˒ᶠ, Ana Kitanovic, PhDᵍ, Linden J. Gearing, PhDᵍ, Frederik Heinrich, PhDᵍ˒ʰ, Pawel Durek, PhDᵍ˒ʰ, Katrin Lehmann, MScᵍ, Mir-Farzin Mashreghi, PhDᵍ, Peter Ewert, MDᵃ˒ᵇ, Thomas Fröhlich, PhDᵈ, Joachim P. Schmitt, MDⁱ, Nadine Spielmann, PhDʲ, Martin Hrabě de Angelis, PhDʲ, Manuel Schmid, MDᵉ˒ᵏ˒ˡ, Christopher N. Toepfer, PhDᵉ˒ᵏ˒ˡ, Eicke Latz, MD, PhDᵍ, Karin Klingel, MDᵐ, Gianluca Santamaria, PhDᶜ˒ᶠ˒ⁿ, Jonathan G. Seidman, PhDᵉ, Christine E. Seidman, MDᵉ, and Cordula M. Wolf, MDᵃ˒ᵇ

ᵃ Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Centre Munich, Technical University of Munich, School of Medicine and Health, Munich, Germany
ᵇ DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
ᶜ Department of Experimental and Clinical Medicine, “Magna Graecia” University of Catanzaro, Catanzaro, Italy
ᵈ Laboratory for Functional Genome Analysis LAFUGA, Gene Center, LMU Munich, Munich, Germany
ᵉ Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
ᶠ First Department of Medicine and Regenerative Medicine in Cardiovascular Diseases, Klinikum Rechts der Isar, School of Medicine and Health, Technical University of Munich, Germany
ᵍ German Rheumatism Research Centre, Berlin, Germany
ʰ Zuse Institute Berlin, Berlin, Germany
ⁱ Institute of Pharmacology, University Hospital Düsseldorf and Cardiovascular Research Institute Düsseldorf (CARID), Heinrich-Heine-University, Düsseldorf, Germany
ʲ Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany
ᵏ Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
ˡ Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
ᵐ Cardiopathology, Institute for Pathology and Neuropathology, University Hospital of Tübingen, Tübingen, Germany
ⁿ Interdepartmental Center of Services (CIS), Omics Sciences and Biobank, “Magna Graecia” University, Catanzaro, Italy

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Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

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Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.