RT Journal Article
SR Electronic
T1 Kynurenic acid, a key L-tryptophan-derived metabolite, protects the heart from an ischemic damage
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.17.492275
DO 10.1101/2022.05.17.492275
A1 Einat Bigelman
A1 Metsada Pasmanik-Chor
A1 Bareket Dassa
A1 Maxim Itkin
A1 Sergey Malitsky
A1 Orly Dorot
A1 Edward Pichinuk
A1 Smadar Levin-Zaidman
A1 Nili Dezorella
A1 Atan Gross
A1 Anastasia Abashidze
A1 Yuval Kleinberg
A1 Gad Keren
A1 Michal Entin-Meer
YR 2022
UL http://biorxiv.org/content/early/2022/05/17/2022.05.17.492275.abstract
AB Background Renal injury induces major changes in plasma and cardiac metabolites. We sought to identify a key metabolite that may affect cardiac mitochondria following an acute kidney injury (AKI) that may be harnessed to protect the heart following an acute ischemic event.Methods and Results Metabolomics profiling of cardiac lysates and plasma samples derived from rats that underwent AKI 1 or 7 days earlier by 5/6 nephrectomy versus sham-operated controls was performed. We detected only 26 differential metabolites in both heart and plasma samples at the two selected time points, relative to sham. Out of which, kynurenic acid (kynurenate, KYNA) seemed most relevant. Interestingly, KYNA given at 10 mM concentration significantly rescued the viability of H9C2 cardiac myoblast cells grown under anoxic conditions and largely improved their mitochondrial structure and function as determined by flow cytometry and cell staining with MitoTracker dyes. Moreover, KYNA diluted in the drinking water of animals induced with an acute myocardial infarction, highly enhanced their cardiac recovery according to echocardiography and histopathology.Conclusion and translational aspect KYNA may represent a key metabolite absorbed by the heart following AKI. This metabolite can enhance cardiac cell viability following an ischemic event in a mechanism that is mediated, at least in part, by the protection of the cardiac mitochondria. A short-term administration of KYNA may be highly beneficial in the treatment of the acute phase of kidney disease in order to attenuate progression to CRS and in ischemic cardiac conditions to reduce ischemic myocardial damage.HighlightsThe levels of the L-Tryptophan-derived metabolite, Kynurenic acid (KYNA), are significantly elevated in the heart and the plasma of animals induced with an acute kidney disease.KYNA rescues the viability of cardiac cells from an ischemic damage both in vitro and in vivo.KYNA can protect the structure & function of cardiac mitochondria in H9C2 cardiomyoblast cells upon exposure to anoxia.Competing Interest StatementThe authors have declared no competing interest.