Thanks to our amazing collaborators: ToniVidalPuig GuillaumeBidau, ThomasKrieg, MikePMurphy + IMS, MBU, EMIT, and @AstraZeneca team.
Proud of this @British Heart Foundation-supported science!

Loss of RET-ROS at complex I induces diastolic dysfunction in mice that is reversed by aerobic exercise | American Journal of Physiology-Heart and Circulatory Physiology | American Physiological Society Central to the development of heart failure with preserved ejection fraction (HFpEF) is the redox disruption of metabolic processes, however, the underlying mechanisms are not fully understood. This study utilized a murine model (ND6) carrying a homoplasmic mitochondrial DNA point mutation (ND6 G13997A), which maintains functional NADH oxidation but lacks the site-specific reactive oxygen species (ROS) generation via reverse electron transport (RET). We demonstrate that mice with RET-ROS deficiency have reduced exercise capacity despite higher lean body mass, impaired resilience to high-fat/high-sucrose dietary stress, and cardiac hypertrophy with diastolic dysfunction. Importantly, dobutamine-induced stress elevated succinate levels in the heart, accompanied by RET-ROS production in WT but not in ND6 mice. Furthermore, ND6 mice showed perturbation in metabolite profiles following dobutamine stress. Mechanistically, the ND6 heart had an upregulated expression of fatty acid transport, oxidation, and synthesis genes (CD36, Cpt1b, Acly, Fas, Elovl6 and Scd1) and increased protein levels of lipid metabolism regulators (acetyl-CoA carboxylase and perilipin 2). Interestingly, 8 weeks of forced treadmill running increased acetyl-CoA abundance, alleviated metabolic stress, and improved diastolic function in RET-ROS mutant hearts. In summary, these findings reveal a critical role for RET-ROS in regulating exercise capacity and cardiometabolic health, identifying it as a potentially selective target for modulating cardiac metabolism.

🚨 New paper out!
A great academia–industry collab reveals a novel role for mitochondrial RET-ROS in #HFpEF.
🧬 ND6 mutation ➡️
🫀 Hypertrophy
💔 Diastolic dysfunction
🏃‍♂️ ↓ Exercise capacity
💪 ↑ Lean mass
🍩 HFD worsened metabolism
✅ Exercise reversed many effects!
🔗 doi.org/10.1152/ajph...

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@cambridgecardio.bsky.social

Delighted to share our lab's review & Ankur Saini's first-author paper! 🚴‍♂️💓 We explore cellular & molecular adaptations to exercise in the aging heart. 🤔💡 Highlighting sex differences & mitochondrial roles. 🙏 to Reviewers & @JCA for a smooth process! www.oaepublish.com/articles/jca...

Christmas edition Tiramisu that Alex made was the best I ever had! 😍