Methods for predicting and treating cardiac dysfunction

Ageing myocardium undergoes structural and functional changes characterized by progressive cardiomyocyte hypertrophy, interstitial fibrosis and inflammation ultimately leading to diastolic and systolic dysfunction. Whilst most focus has been placed on established risk factors such as dyslipidaemia, hypertension and obesity in accelerating cardiac ageing, a potential role for amino acids has received little attention. Here the inventors show that increased phenylalanine (PA) levels induced in vitro cytosolic oxidative stress and senescence whilst in vivo led to senile-like cardiac deterioration in young mice. Moreover, they demonstrated that hepatic PA catabolism declined with age in a p21-dependent manner, whilst p21 deficiency prevented age-related cardiac dysfunction. Finally, the inventors found that Pah cofactor BH4 reversed the age-related rise in plasma PA levels and senile cardiac alterations. These observations have immediate implications for promoting cardiac health and healthspan and suggest that phenylalanine can be used as a biomarker and biotarget of cardiac dysfunction.

Patent Application number: 19186370.3
Publications:
Circulation . 2021 Aug 17;144(7):559-574. doi: 10.1161/CIRCULATIONAHA.121.054204. Epub 2021 Jun 24.

Reference:

BIO19286-T1

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Aymeric Empereur
Aymeric Empereur
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Patent filling date: 2019-07-15

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