Why the study?
Heart failure with preserved ejection fraction lacks effective treatments and involves mitochondrial dysfunctions related to an imbalance of fusion and fission, but the underlying molecular mechanisms remain to be investigated.
PINK1-mediated phosphorylation of Drp1S616 improves mitochondrial fission and function, thereby slowing the progression of HFpEF in a preclinical rat model.
May offer novel HFpEF target via mitochondrial fission; animal data leave translation to humans uncertain.
Background: Heart failure with preserved ejection fraction (HFpEF) is a major subtype of HF with no effective treatments. Mitochondrial dysfunctions relevant to the imbalance of fusion and fission occur in HFpEF. The aim of the study is to investigate molecular mechanisms of mitochondrial dysfunctions in HFpEF. Methods and Results: The HFpEF model was established by feeding Dahl/SS rats with high salt, showing risk factors such as hypertension, mitochondrial dysfunctions and so on. Physiological and biological measurements showed a decrease in the expression of mitochondrial function related genes, ATP production, and mitochondrial fission index in HFpEF. PINK1 knockout in H9C2 cardiomyocytes also showed the same effects. Moreover, PINK1 myocardium-specific overexpression to HFpEF rats activated the Drp1 S616 phosphorylation and enhanced the mitochondrial fission to slow the progression of HFpEF. Conclusions: PINK1 can phosphorylate Drp1 S616 to improve mitochondrial fission, relieve mitochondrial dysfunctions and slow the progression of HFpEF, which highlights the potential treatment of HFpEF.
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Shou et al. (2022) studied this question.
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