Dissecting the Mechanisms Whereby Tryptophan Metabolites Alter Myocardial Function

Abstract

Cardiovascular diseases (CVD) are a significant cause of morbidity and mortality, especially in the elderly population and they represent an important risk factor for frailty. The essential amino acid, tryptophan (TRP), acts as a precursor of neurotransmitters/hormones, such as serotonin and melatonin, and is central to many aspects of cellular metabolism. TRP degradation, however, can lead to breakdown products, such as kynurenine (KYN), whose impact on normal and diseased hearts remains primarily unknown. Moreover, in recent clinical reports, increased levels of KYN and/or its metabolites, formed via degradation of the essential amino acid tryptophan, are associated with heart diseases and atherosclerosis. KYN infusion significantly impaired cardiac function in Langendorff‐perfused hearts. Similarly in isolated cardiomyocytes, exposure to KYN increased oxidative stress and decreased fractional shortening. The ongoing studies include mechanistic approaches to determine the pathways involved in KYN and/or its metabolites’ impact on myocardial function.