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Cardiometabolic Biomarkers

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

Deadline for manuscript submissions: closed (31 May 2020) | Viewed by 30221

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Guest Editor
Department of Biomedical Sciences for Health, University of Milan, 00133 Milan, Italy
Interests: cardiometabolic disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiometabolic diseases can be present long before becoming clinically apparent. Accurate molecular predictors of disease are of particular importance since the delay or prevention of morbidity is possible via pharmacological and behavioral interventions. Metabolomics is increasingly applied to molecular biomarker discovery. Large epidemiological cohort studies can assess whether metabolite biomarkers improve upon existing disease markers. Furthermore, experimental work in model systems and integration with other functional genomic approaches will facilitate the discovery of causal links between select molecular biomarkers and disease pathogenesis.

Cardiometabolic diseases are difficult for physicians to manage because they can be present for years before becoming clinically apparent. Despite strong statistical associations with outcomes, new  molecular biomarkers often contribute less than expected to the accuracy of risk models because many report on the same pathways as preexisting disease markers. New predictors of molecular biomarkers may also identify patients who are likely to respond to specific interventions, moving toward a goal of more personalized medicine.

Biomarkers can assist in the care of patients without apparent disease (screening biomarkers), with a suspected disease (diagnostic biomarkers), or with progression or remission of overt disease (prognostic biomarkers). Biomarkers that participate in molecular disease pathways are the most likely candidates for disease surrogates—substitutes for a clinical endpoint.

Prof. Dr. Massimiliano M. Corsi Romanelli
Guest Editor

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Keywords

  • Inflammasome markers
  • Cardiac fibrosis molecular markers
  • Epicardial adipose tissue and molecular pathway
  • sRAGE and glycation
  • GLP-1 receptor and molecular biomarkers in obesity
  • Chemochines and cytokines and their receptors as molecular biomarker

Published Papers (6 papers)

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Research

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15 pages, 4065 KiB  
Article
Early Elevation of Systemic Plasma Clusterin after Reperfused Acute Myocardial Infarction in a Preclinical Porcine Model of Ischemic Heart Disease
by Denise Traxler, Andreas Spannbauer, Patrick Einzinger, Julia Mester-Tonczar, Dominika Lukovic, Johannes Winkler, Katrin Zlabinger, Alfred Gugerell, Ljubica Mandic, Mariann Gyöngyösi and Noemi Pavo
Int. J. Mol. Sci. 2020, 21(13), 4591; https://doi.org/10.3390/ijms21134591 - 28 Jun 2020
Cited by 5 | Viewed by 2593
Abstract
Clusterin exerts anti-inflammatory, cytoprotective and anti-apoptotic effects. Both an increase and decrease of clusterin in acute myocardial infarction (AMI) has been reported. We aimed to clarify the role of clusterin as a systemic biomarker in AMI. AMI was induced by percutaneous left anterior [...] Read more.
Clusterin exerts anti-inflammatory, cytoprotective and anti-apoptotic effects. Both an increase and decrease of clusterin in acute myocardial infarction (AMI) has been reported. We aimed to clarify the role of clusterin as a systemic biomarker in AMI. AMI was induced by percutaneous left anterior artery (LAD) occlusion for 90 min followed by reperfusion in 24 pigs. Contrast ventriculography was performed after reperfusion to assess left ventricular ejection fraction (LVEF), left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV) and additional cMRI + late enhancement to measure infarct size and LV functions at day 3 and week 6 post-MI. Blood samples were collected at prespecified timepoints. Plasma clusterin and other biomarkers (cTnT, NT-proBNP, neprilysin, NGAL, ET-1, osteopontin, miR21, miR29) were measured by ELISA and qPCR. Gene expression profiles of infarcted and remote region 3 h (n = 5) and 3 days (n = 5) after AMI onset were analysed by RNA-sequencing. AMI led to an increase in LVEDV and LVESV during 6-week, with concomitant elevation of NT-proBNP 3-weeks after AMI. Plasma clusterin levels were increased immediately after AMI and returned to normal levels until 3-weeks. Plasma NGAL, ET-1 and miR29 was significantly elevated at 3 weeks follow-up, miR21 increased after reperfusion and at 3 weeks post-AMI, while circulating neprilysin levels did not change. Elevated plasma clusterin levels 120 min after AMI onset suggest that clusterin might be an additional early biomarker of myocardial ischemia. Full article
(This article belongs to the Special Issue Cardiometabolic Biomarkers)
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Review

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13 pages, 742 KiB  
Review
Osteopontin: The Molecular Bridge between Fat and Cardiac–Renal Disorders
by Elena Vianello, Marta Kalousová, Elena Dozio, Lorenza Tacchini, Tomáš Zima and Massimiliano Marco Corsi Romanelli
Int. J. Mol. Sci. 2020, 21(15), 5568; https://doi.org/10.3390/ijms21155568 - 4 Aug 2020
Cited by 17 | Viewed by 3711
Abstract
Osteopontin (OPN) is a multifaceted matricellular protein, with well-recognized roles in both the physiological and pathological processes in the body. OPN is expressed in the main organs and cell types, in which it induces different biological actions. During physiological conditioning, OPN acts as [...] Read more.
Osteopontin (OPN) is a multifaceted matricellular protein, with well-recognized roles in both the physiological and pathological processes in the body. OPN is expressed in the main organs and cell types, in which it induces different biological actions. During physiological conditioning, OPN acts as both an intracellular protein and soluble excreted cytokine, regulating tissue remodeling and immune-infiltrate in adipose tissue the heart and the kidney. In contrast, the increased expression of OPN has been correlated with the severity of the cardiovascular and renal outcomes associated with obesity. Indeed, OPN expression is at the “cross roads” of visceral fat extension, cardiovascular diseases (CVDs) and renal disorders, in which OPN orchestrates the molecular interactions, leading to chronic low-grade inflammation. The common factor associated with OPN overexpression in adipose, cardiac and renal tissues seems attributable to the concomitant increase in visceral fat size and the increase in infiltrated OPN+ macrophages. This review underlines the current knowledge on the molecular interactions between obesity and the cardiac–renal disorders ruled by OPN. Full article
(This article belongs to the Special Issue Cardiometabolic Biomarkers)
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25 pages, 851 KiB  
Review
Long Non-Coding RNAs in Atrial Fibrillation: Pluripotent Stem Cell-Derived Cardiomyocytes as a Model System
by Emre Bektik, Douglas B. Cowan and Da-Zhi Wang
Int. J. Mol. Sci. 2020, 21(15), 5424; https://doi.org/10.3390/ijms21155424 - 30 Jul 2020
Cited by 10 | Viewed by 3408
Abstract
Atrial fibrillation (AF) is a type of sustained arrhythmia in humans often characterized by devastating alterations to the cardiac conduction system as well as the structure of the atria. AF can lead to decreased cardiac function, heart failure, and other complications. Long non-coding [...] Read more.
Atrial fibrillation (AF) is a type of sustained arrhythmia in humans often characterized by devastating alterations to the cardiac conduction system as well as the structure of the atria. AF can lead to decreased cardiac function, heart failure, and other complications. Long non-coding RNAs (lncRNAs) have been shown to play important roles in the cardiovascular system, including AF; however, a large group of lncRNAs is not conserved between mouse and human. Furthermore, AF has complex networks showing variations in mechanisms in different species, making it challenging to utilize conventional animal models to investigate the functional roles and potential therapeutic benefits of lncRNAs for AF. Fortunately, pluripotent stem cell (PSC)-derived cardiomyocytes (CMs) offer a reliable platform to study lncRNA functions in AF because of certain electrophysiological and molecular similarities with native human CMs. In this review, we first summarize the broad aspects of lncRNAs in various heart disease settings, then focus on their potential roles in AF development and pathophysiology. We also discuss current uses of PSCs in AF research and describe how these studies could be developed into novel therapeutics for AF and other cardiovascular diseases. Full article
(This article belongs to the Special Issue Cardiometabolic Biomarkers)
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13 pages, 1796 KiB  
Review
Multifactorial Activation of NLRP3 Inflammasome: Relevance for a Precision Approach to Atherosclerotic Cardiovascular Risk and Disease
by Andrea Baragetti, Alberico Luigi Catapano and Paolo Magni
Int. J. Mol. Sci. 2020, 21(12), 4459; https://doi.org/10.3390/ijms21124459 - 23 Jun 2020
Cited by 22 | Viewed by 3641
Abstract
Chronic low-grade inflammation, through the specific activation of the NACHT leucine-rich repeat- and PYD-containing (NLRP)3 inflammasome-interleukin (IL)-1β pathway, is an important contributor to the development of atherosclerotic cardiovascular disease (ASCVD), being triggered by intracellular cholesterol accumulation within cells. Within this pathological context, this [...] Read more.
Chronic low-grade inflammation, through the specific activation of the NACHT leucine-rich repeat- and PYD-containing (NLRP)3 inflammasome-interleukin (IL)-1β pathway, is an important contributor to the development of atherosclerotic cardiovascular disease (ASCVD), being triggered by intracellular cholesterol accumulation within cells. Within this pathological context, this complex pathway is activated by a number of factors, such as unhealthy nutrition, altered gut and oral microbiota, and elevated cholesterol itself. Moreover, evidence from autoinflammatory diseases, like psoriasis and others, which are also associated with higher cardiovascular disease (CVD) risk, suggests that variants of NLRP3 pathway-related genes (like NLRP3 itself, caspase recruitment domain-containing protein (CARD)8, caspase-1 and IL-1β) may carry gain-of-function mutations leading, in some individuals, to a constitutive pro-inflammatory pattern. Indeed, some reports have recently associated the presence of specific single nucleotide polymorphisms (SNPs) on such genes with greater ASCVD prevalence. Based on these observations, a potential effective strategy in this context may be the identification of carriers of these NLRP3-related SNPs, to generate a genomic score, potentially useful for a better CVD risk prediction, and, possibly, for personalized therapeutic approaches targeted to the NLRP3-IL-1β pathway. Full article
(This article belongs to the Special Issue Cardiometabolic Biomarkers)
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19 pages, 2000 KiB  
Review
On the Road to Accurate Biomarkers for Cardiometabolic Diseases by Integrating Precision and Gender Medicine Approaches
by Letizia Scola, Rosa Maria Giarratana, Salvatore Torre, Vincenzo Argano, Domenico Lio and Carmela Rita Balistreri
Int. J. Mol. Sci. 2019, 20(23), 6015; https://doi.org/10.3390/ijms20236015 - 29 Nov 2019
Cited by 15 | Viewed by 4152
Abstract
The need to facilitate the complex management of cardiometabolic diseases (CMD) has led to the detection of many biomarkers, however, there are no clear explanations of their role in the prevention, diagnosis or prognosis of these diseases. Molecules associated with disease pathways represent [...] Read more.
The need to facilitate the complex management of cardiometabolic diseases (CMD) has led to the detection of many biomarkers, however, there are no clear explanations of their role in the prevention, diagnosis or prognosis of these diseases. Molecules associated with disease pathways represent valid disease surrogates and well-fitted CMD biomarkers. To address this challenge, data from multi-omics types (genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, and nutrigenomics), from human and animal models, have become available. However, individual omics types only provide data on a small part of molecules involved in the complex CMD mechanisms, whereas, here, we propose that their integration leads to multidimensional data. Such data provide a better understanding of molecules related to CMD mechanisms and, consequently, increase the possibility of identifying well-fitted biomarkers. In addition, the application of gender medicine also helps to identify accurate biomarkers according to gender, facilitating a differential CMD management. Accordingly, the impact of gender differences in CMD pathophysiology has been widely demonstrated, where gender is referred to the complex interrelation and integration of sex (as a biological and functional marker of the human body) and psychological and cultural behavior (due to ethnical, social, and religious background). In this review, all these aspects are described and discussed, as well as potential limitations and future directions in this incipient field. Full article
(This article belongs to the Special Issue Cardiometabolic Biomarkers)
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13 pages, 526 KiB  
Review
Epicardial Adipose Tissue: Clinical Biomarker of Cardio-Metabolic Risk
by Alexandra C. Villasante Fricke and Gianluca Iacobellis
Int. J. Mol. Sci. 2019, 20(23), 5989; https://doi.org/10.3390/ijms20235989 - 28 Nov 2019
Cited by 109 | Viewed by 11889
Abstract
Epicardial adipose tissue (EAT) is part of the visceral adipose tissue (VAT) that surrounds the heart and it is a quantifiable, modifiable, and multifaceted tissue that has both local and systemic effects. When EAT is enlarged, EAT contributes to atherosclerotic cardiovascular disease (ASCVD) [...] Read more.
Epicardial adipose tissue (EAT) is part of the visceral adipose tissue (VAT) that surrounds the heart and it is a quantifiable, modifiable, and multifaceted tissue that has both local and systemic effects. When EAT is enlarged, EAT contributes to atherosclerotic cardiovascular disease (ASCVD) risk and plays a role in the development of metabolic syndrome (MetS). In this review, we will discuss the role of EAT in various facets of MetS, including type 2 diabetes mellitus (T2DM) and insulin resistance. We examine the association between EAT and liver steatosis. We also address the correlations of EAT with HIV therapy and with psoriasis. We discuss racial differences in baseline EAT thickness. We conclude that EAT measurement serves as a powerful potential diagnostic tool in assessing cardiovascular and metabolic risk. Measurement of EAT is made less costly, more convenient, and yet accurate and reliable by transthoracic echocardiography. Furthermore, modification of EAT thickness has therapeutic implications for ASCVD, T2DM, and MetS. Full article
(This article belongs to the Special Issue Cardiometabolic Biomarkers)
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