Journal article
Integrated Multilayer Omics Reveals the Genomic, Proteomic, and Metabolic Influences of Histidyl Dipeptides on the Heart
Journal of the American Heart Association, Vol.11(13), pp.e023868-e023868
07/05/2022
DOI: 10.1161/JAHA.121.023868
PMCID: PMC9333374
PMID: 35730646
Abstract
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 mice. Our result showed that higher myocardial levels of histidyl dipeptides were associated with extensive changes in the levels of several microRNAs, which target the expression of contractile proteins, beta-fatty acid oxidation, and citric acid cycle (TCA) enzymes. Global proteomic analysis showed enrichment in the expression of contractile proteins, enzymes of beta-fatty acid oxidation, and the TCA in the Carns transgenic heart. Under aerobic conditions, the Carns transgenic hearts had lower levels of short- and long-chain fatty acids as well as the TCA intermediate-succinic acid; whereas, under ischemic conditions, the accumulation of fatty acids and TCA intermediates was significantly attenuated. Integration of multiple data sets suggested that beta-fatty acid oxidation and TCA pathways exhibit correlative changes in the Carns transgenic hearts at all 3 levels. Conclusions Taken together, these findings reveal a central role of histidyl dipeptides in coordinated regulation of myocardial structure, function, and energetics.
Details
- Title: Subtitle
- Integrated Multilayer Omics Reveals the Genomic, Proteomic, and Metabolic Influences of Histidyl Dipeptides on the Heart
- Creators
- Keqiang Yan - Chinese Acad Sci, Beijing Inst Genom, Beishan Ind Zone, Shenzhen, Peoples R ChinaZhanlong Mei - BGI Group (China)Jingjing Zhao - University of LouisvilleMd Aminul Islam Prodhan - University of LouisvilleDetlef Obal - Stanford MedicineKartik Katragadda - University of LouisvilleBenjamin Doelling - University of LouisvilleDavid Hoetker - University of LouisvilleDheeraj Kumar Posa - University of LouisvilleLiqing He - University of LouisvilleXinmin Yin - University of LouisvilleJasmit Shah - Aga Khan University NairobiJianmin Pan - University of LouisvilleShesh Rai - University of LouisvillePawel Konrad Lorkiewicz - University of LouisvilleXiang Zhang - University of LouisvilleSiqi Liu - BGI Group (China)Aruni Bhatnagar - University of LouisvilleShahid P. Baba - University of Louisville
- Resource Type
- Journal article
- Publication Details
- Journal of the American Heart Association, Vol.11(13), pp.e023868-e023868
- DOI
- 10.1161/JAHA.121.023868
- PMID
- 35730646
- PMCID
- PMC9333374
- NLM abbreviation
- J Am Heart Assoc
- ISSN
- 2047-9980
- eISSN
- 2047-9980
- Publisher
- Wiley
- Number of pages
- 29
- Grant note
- GN210596F / Jewish Heritage Fund for Excellence R01HL122581-01; R01HL 55 477; GM127607 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 07/05/2022
- Academic Unit
- Anesthesia
- Record Identifier
- 9984696581602771
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