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The Impact of Altered Metabolism on Cardiac Development and Disease
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The Impact of Altered Metabolism on Cardiac Development and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 7460

Special Issue Editor

Dr. Ethan David Cohen

E-Mail Website
Guest Editor
School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA
Interests: heart development; intercellular signaling; glucocorticoids; cardiomyocytes; Wnt signaling

Special Issue Information

Dear Colleagues,

The heart is the first organ formed during embryogenesis and continues its rhythmic contractions throughout the entirety of life. Therefore, it is essential for the heart to adapt to the changes in nutrient availability, oxygen tension, and workload that occur over a lifetime. While the heart utilizes glycolysis to produce ATP in a relatively hypoxic amnionic environment, it becomes reliant on mitochondrial respiration as oxygen levels rise at birth. The heart initially uses lactate and glucose to fuel oxidative phosphorylation but later depends on the b-oxidation of fatty acids for the vast amount of ATP required for adult circulation. Cardiac metabolism is thus dynamic and must be tightly coupled to the heart’s structural and functional maturation. Genetic and environmental insults that alter metabolism can thus impact both cardiac development and the heart’s responses to ischemia, pressure overload and other injuries.  This Special Issue of the International Journal of Molecular Sciences will focus on how altered cardiac metabolism affects the growth, differentiation, maturation and function of the cardiomyocytes, endocardial cells, fibroblasts, and other cell types within the heart.

Dr. Ethan David Cohen
Guest Editor

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Published Papers (3 papers)

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Research

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15 pages, 2768 KiB  
Article
Novel Genes Involved in Hypertrophic Cardiomyopathy: Data of Transcriptome and Methylome Profiling
by Ivan Kiselev, Maxim Kozin, Natalia Baulina, Maria Pisklova, Ludmila Danilova, Alexandr Zotov, Olga Chumakova, Dmitry Zateyshchikov and Olga Favorova
Int. J. Mol. Sci. 2022, 23(23), 15280; https://doi.org/10.3390/ijms232315280 - 3 Dec 2022
Cited by 3 | Viewed by 2093
Abstract
Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease; its pathogenesis is still being intensively studied to explain the reasons for the significant genetic and phenotypic heterogeneity of the disease. To search for new genes involved in HCM development, we analyzed gene [...] Read more.
Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease; its pathogenesis is still being intensively studied to explain the reasons for the significant genetic and phenotypic heterogeneity of the disease. To search for new genes involved in HCM development, we analyzed gene expression profiles coupled with DNA methylation profiles in the hypertrophied myocardia of HCM patients. The transcriptome analysis identified significant differences in the levels of 193 genes, most of which were underexpressed in HCM. The methylome analysis revealed 1755 nominally significant differentially methylated positions (DMPs), mostly hypomethylated in HCM. Based on gene ontology enrichment analysis, the majority of biological processes, overrepresented by both differentially expressed genes (DEGs) and DMP-containing genes, are involved in the regulation of locomotion and muscle structure development. The intersection of 193 DEGs and 978 DMP-containing genes pinpointed eight common genes, the expressions of which correlated with the methylation levels of the neighboring DMPs. Half of these genes (AUTS2, BRSK2, PRRT1, and SLC17A7), regulated by the mechanism of DNA methylation, were underexpressed in HCM and were involved in neurogenesis and synapse functioning. Our data, suggesting the involvement of innervation-associated genes in HCM, provide additional insights into disease pathogenesis and expand the field of further research. Full article
(This article belongs to the Special Issue The Impact of Altered Metabolism on Cardiac Development and Disease)
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Review

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18 pages, 340 KiB  
Review
Metabolomics in Pulmonary Hypertension—A Useful Tool to Provide Insights into the Dark Side of a Tricky Pathology
by Pier Paolo Bassareo and Michele D’Alto
Int. J. Mol. Sci. 2023, 24(17), 13227; https://doi.org/10.3390/ijms241713227 - 25 Aug 2023
Cited by 1 | Viewed by 1435
Abstract
Pulmonary hypertension (PH) is a multifaceted illness causing clinical manifestations like dyspnea, fatigue, and cyanosis. If left untreated, it often evolves into irreversible pulmonary arterial hypertension (PAH), leading to death. Metabolomics is a laboratory technique capable of providing insights into the metabolic pathways [...] Read more.
Pulmonary hypertension (PH) is a multifaceted illness causing clinical manifestations like dyspnea, fatigue, and cyanosis. If left untreated, it often evolves into irreversible pulmonary arterial hypertension (PAH), leading to death. Metabolomics is a laboratory technique capable of providing insights into the metabolic pathways that are responsible for a number of physiologic or pathologic events through the analysis of a biological fluid (such as blood, urine, and sputum) using proton nuclear magnetic resonance spectroscopy or mass spectrometry. A systematic review was finalized according to the PRISMA scheme, with the goal of providing an overview of the research papers released up to now on the application of metabolomics to PH/PAH. So, eighty-five papers were identified, of which twenty-four concerning PH, and sixty-one regarding PAH. We found that, from a metabolic standpoint, the hallmarks of the disease onset and progression are an increase in glycolysis and impaired mitochondrial respiration. Oxidation is exacerbated as well. Specific metabolic fingerprints allow the characterization of some of the specific PH and PAH subtypes. Overall, metabolomics provides insights into the biological processes happening in the body of a subject suffering from PH/PAH. The disarranged metabolic pathways underpinning the disease may be the target of new therapeutic agents. Metabolomics will allow investigators to make a step forward towards personalized medicine. Full article
(This article belongs to the Special Issue The Impact of Altered Metabolism on Cardiac Development and Disease)
17 pages, 365 KiB  
Review
Gender Differences and Cardiometabolic Risk: The Importance of the Risk Factors
by Antonella Meloni, Christian Cadeddu, Lucia Cugusi, Maria Pia Donataccio, Martino Deidda, Susanna Sciomer, Sabina Gallina, Cristina Vassalle, Federica Moscucci, Giuseppe Mercuro and Silvia Maffei
Int. J. Mol. Sci. 2023, 24(2), 1588; https://doi.org/10.3390/ijms24021588 - 13 Jan 2023
Cited by 19 | Viewed by 3385
Abstract
Metabolic syndrome (Mets) is a clinical condition characterized by a cluster of major risk factors for cardiovascular disease (CVD) and type 2 diabetes: proatherogenic dyslipidemia, elevated blood pressure, dysglycemia, and abdominal obesity. Each risk factor has an independent effect, but, when aggregated, they [...] Read more.
Metabolic syndrome (Mets) is a clinical condition characterized by a cluster of major risk factors for cardiovascular disease (CVD) and type 2 diabetes: proatherogenic dyslipidemia, elevated blood pressure, dysglycemia, and abdominal obesity. Each risk factor has an independent effect, but, when aggregated, they become synergistic, doubling the risk of developing cardiovascular diseases and causing a 1.5-fold increase in all-cause mortality. We will highlight gender differences in the epidemiology, etiology, pathophysiology, and clinical expression of the aforementioned Mets components. Moreover, we will discuss gender differences in new biochemical markers of metabolic syndrome and cardiovascular risk. Full article
(This article belongs to the Special Issue The Impact of Altered Metabolism on Cardiac Development and Disease)
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