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Integrated Multilayer Omics Reveals The Genomic, Proteomic, And Metabolic Influences Of Histidyl Dipeptides On The Heart, Keqiang Yan, Zhanlong Mei, Jingjing Zhao, Md Aminul Islam Prodhan, Detlef Obal, Kartik Katragadda, Benjamin Doelling, David Hoetker, Dheeraj Kumar Posa
Integrated Multilayer Omics Reveals The Genomic, Proteomic, And Metabolic Influences Of Histidyl Dipeptides On The Heart, Keqiang Yan, Zhanlong Mei, Jingjing Zhao, Md Aminul Islam Prodhan, Detlef Obal, Kartik Katragadda, Benjamin Doelling, David Hoetker, Dheeraj Kumar Posa
Internal Medicine, East Africa
Background: Histidyl dipeptides such as carnosine are present in a micromolar to millimolar range in mammalian hearts. These dipeptides facilitate glycolysis by proton buffering. They form conjugates with reactive aldehydes, such as acrolein, and attenuate myocardial ischemia-reperfusion injury. Although these dipeptides exhibit multifunctional properties, a composite understanding of their role in the myocardium is lacking.
Methods and Results: To identify histidyl dipeptide-mediated responses in the heart, we used an integrated triomics approach, which involved genome-wide RNA sequencing, global proteomics, and unbiased metabolomics to identify the effects of cardiospecific transgenic overexpression of the carnosine synthesizing enzyme, carnosine synthase (Carns), in …