Molecular Biomarkers In Cardiology

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 55070

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Guest Editor
Cardiology Section, Hospital “F. Perinei” Altamura (BA), 70022 Altamura, Italy
Interests: heart failure; preventive cardiology; vascular biology; endothelial function; cardiovascular pharmacology
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Dear Colleagues,

Cardiovascular diseases still represent the major cause of death worldwide. The need for preventing the acute onset of such diseases and to predict their occurrence is the major goal of medicine. By succeeding in preventing the negative consequences of cardiovascular diseases, physicians can prevent both mortality and morbidities of the patients. Therefore, the implementation in quality of life and the reduction in the financial burden of health due to the reduced impact of chronic comorbidities related to cardiovascular diseases will also improve the economics of the nations.

The use of biomarkers is the key for conquering the tip of this target-mountain.

Indeed, the ideal biomarkers should be sensitive and specific, able to detect the onset of pathologies early and in time to allow physicians to counteract the exploit of the disease.

Biomolecular approaches for early identification of cardiovascular diseases before their onset are an attractive field in cardiology. There is little evidence about the perfect biomarker able to identify the unstable atherosclerotic plaque, the occurrence of aortic dissection, or the incipient onset of heart failure.

The aim of this Special Issue is to offer the readers the best overview about the current state of knowledge of biomolecular biomarkers in cardiovascular diseases.

Dr. Pietro Scicchitano
Guest Editor

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Keywords

  • Biomolecules
  • Biomarkers
  • Atherosclerotic plaques instability
  • Heart failure
  • Prognosis and diagnosis

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Published Papers (16 papers)

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16 pages, 1583 KiB  
Article
Nourin-Dependent miR-137 and miR-106b: Novel Early Inflammatory Diagnostic Biomarkers for Unstable Angina Patients
by Salwa A. Elgebaly, Robert H. Christenson, Hossam Kandil, Nashwa El-Khazragy, Laila Rashed, Beshoy Yacoub, Heba Eldeeb, Mahmoud Ali, Roshanak Sharafieh, Ulrike Klueh and Donald L. Kreutzer
Biomolecules 2021, 11(3), 368; https://doi.org/10.3390/biom11030368 - 28 Feb 2021
Cited by 9 | Viewed by 3646
Abstract
Background: Currently, no blood biomarkers exist that can diagnose unstable angina (UA) patients. Nourin is an early inflammatory mediator rapidly released within 5 min by reversible ischemic myocardium, and if ischemia persists, it is also released by necrosis. Nourin is elevated in acute [...] Read more.
Background: Currently, no blood biomarkers exist that can diagnose unstable angina (UA) patients. Nourin is an early inflammatory mediator rapidly released within 5 min by reversible ischemic myocardium, and if ischemia persists, it is also released by necrosis. Nourin is elevated in acute coronary syndrome (ACS) patients but not in symptomatic noncardiac and healthy subjects. Recently, circulating microRNAs (miRNAs) have been established as markers of disease, including cardiac injury and inflammation. Objectives: To profile and validate the potential diagnostic value of Nourin-dependent miR-137 (marker of cell damage) and miR-106b-5p (marker of inflammation) as early biomarkers in suspected UA patients and to investigate the association of their target and regulating genes. Methods: Using Nourin amino acid sequence, an integrated bioinformatics analysis was conducted. Analysis indicated that Nourin is a direct target for miR-137 and miR-106b-5p in myocardial ischemic injury. Two linked molecular networks of lncRNA/miRNAs/mRNAs were also retrieved, including CTB89H12.4/miR-137/FTHL-17 and CTB89H12.4/miR-106b-5p/ANAPC11. Gene expression profiling was assessed in serum samples collected at presentation to an emergency department (ED) from: (1) UA patients (n = 30) (confirmed by invasive coronary angiography with stenosis greater than 50% and troponin level below the clinical decision limit); (2) patients with acute ST elevation myocardial infarction (STEMI) (n = 16) (confirmed by persistent ST-segment changes and elevated troponin level); and (3) healthy subjects (n = 16). Results: Gene expression profiles showed that miR-137 and miR-106b-5p were significantly upregulated by 1382-fold and 192-fold in UA compared to healthy, and by 2.5-fold and 4.6-fold in STEMI compared to UA, respectively. Healthy subjects showed minimal expression profile. Receiver operator characteristics (ROC) analysis revealed that the two miRNAs were sensitive and specific biomarkers for assessment of UA and STEMI patients. Additionally, Spearman’s correlation analysis revealed a significant association of miRNAs with the associated mRNA targets and the regulating lncRNA. Conclusions: Nourin-dependent gene expression of miR-137 and miR-106b-5p are novel blood-based biomarkers that can diagnose UA and STEMI patients at presentation and stratify severity of myocardial ischemia, with higher expression in STEMI compared to UA. Early diagnosis of suspected UA patients using the novel Nourin biomarkers is key for initiating guideline-based therapy that improves patients’ health outcomes. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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13 pages, 989 KiB  
Article
Sirt1 Activity in PBMCs as a Biomarker of Different Heart Failure Phenotypes
by Valeria Conti, Graziamaria Corbi, Maria Vincenza Polito, Michele Ciccarelli, Valentina Manzo, Martina Torsiello, Emanuela De Bellis, Federica D’Auria, Gennaro Vitulano, Federico Piscione, Albino Carrizzo, Paola Di Pietro, Carmine Vecchione, Nicola Ferrara and Amelia Filippelli
Biomolecules 2020, 10(11), 1590; https://doi.org/10.3390/biom10111590 - 23 Nov 2020
Cited by 7 | Viewed by 2545
Abstract
Heart Failure (HF) is a syndrome, which implies the existence of different phenotypes. The new categorization includes patients with preserved ejection fraction (HFpEF), mid-range EF (HFmrEF), and reduced EF (HFrEF) but the molecular mechanisms involved in these HF phenotypes have not yet been [...] Read more.
Heart Failure (HF) is a syndrome, which implies the existence of different phenotypes. The new categorization includes patients with preserved ejection fraction (HFpEF), mid-range EF (HFmrEF), and reduced EF (HFrEF) but the molecular mechanisms involved in these HF phenotypes have not yet been exhaustively investigated. Sirt1 plays a crucial role in biological processes strongly related to HF. This study aimed to evaluate whether Sirt1 activity was correlated with EF and other parameters in HFpEF, HFmrEF, and HFrEF. Seventy patients, HFpEF (n = 23), HFmrEF (n = 23) and HFrEF (n = 24), were enrolled at the Cardiology Unit of the University Hospital of Salerno. Sirt1 activity was measured in peripheral blood mononuclear cells (PBMCs). Angiotensin-Converting Enzyme 2 (ACE2) activity, Tumor Necrosis Factor-alpha (TNF-α) and Brain Natriuretic Peptide (BNP) levels were quantified in plasma. HFpEF showed lower Sirt1 and ACE2 activities than both HFmrEF and HFrEF (p < 0.0001), without difference compared to No HF controls. In HFmrEF and HFrEF a very strong correlation was found between Sirt1 activity and EF (r2 = 0.899 and r2 = 0.909, respectively), and between ACE2 activity and Sirt1 (r2 = 0.801 and r2 = 0.802, respectively). HFrEF showed the highest TNF-α levels without reaching statistical significance. Significant differences in BNP were found among the groups, with the highest levels in the HFrEF. Determining Sirt1 activity in PBMCs is useful to distinguish the HF patients’ phenotypes from each other, especially HFmrEF/HFrEF from HFpEF. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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20 pages, 2838 KiB  
Article
Biophysical and Lipidomic Biomarkers of Cardiac Remodeling Post-Myocardial Infarction in Humans
by Valerie Samouillan, Ignacio Miguel Martinez de Lejarza Samper, Aleyda Benitez Amaro, David Vilades, Jany Dandurand, Josefina Casas, Esther Jorge, David de Gonzalo Calvo, Alberto Gallardo, Enrique Lerma, Jose Maria Guerra, Francesc Carreras, Ruben Leta and Vicenta Llorente Cortes
Biomolecules 2020, 10(11), 1471; https://doi.org/10.3390/biom10111471 - 22 Oct 2020
Cited by 15 | Viewed by 2663
Abstract
Few studies have analyzed the potential of biophysical parameters as markers of cardiac remodeling post-myocardial infarction (MI), particularly in human hearts. Fourier transform infrared spectroscopy (FTIR) illustrates the overall changes in proteins, nucleic acids and lipids in a single signature. The aim of [...] Read more.
Few studies have analyzed the potential of biophysical parameters as markers of cardiac remodeling post-myocardial infarction (MI), particularly in human hearts. Fourier transform infrared spectroscopy (FTIR) illustrates the overall changes in proteins, nucleic acids and lipids in a single signature. The aim of this work was to define the FTIR and lipidomic pattern for human left ventricular remodeling post-MI. A total of nine explanted hearts from ischemic cardiomyopathy patients were collected. Samples from the right ventricle (RV), left ventricle (LV) and infarcted left ventricle (LV INF) were subjected to biophysical (FTIR and differential scanning calorimetry, DSC) and lipidomic (liquid chromatography–high-resolution mass spectrometry, LC–HRMS) studies. FTIR evidenced deep alterations in the myofibers, extracellular matrix proteins, and the hydric response of the LV INF compared to the RV or LV from the same subject. The lipid and esterified lipid FTIR bands were enhanced in LV INF, and both lipid indicators were tightly and positively correlated with remodeling markers such as collagen, lactate, polysaccharides, and glycogen in these samples. Lipidomic analysis revealed an increase in several species of sphingomyelin (SM), hexosylceramide (HexCer), and cholesteryl esters combined with a decrease in glycerophospholipids in the infarcted tissue. Our results validate FTIR indicators and several species of lipids as useful markers of left ventricular remodeling post-MI in humans. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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13 pages, 1368 KiB  
Article
The c.*52 A/G and c.*773 A/G Genetic Variants in the UTR′3 of the LDLR Gene Are Associated with the Risk of Acute Coronary Syndrome and Lower Plasma HDL-Cholesterol Concentration
by Gilberto Vargas-Alarcon, Oscar Perez-Mendez, Julian Ramirez-Bello, Rosalinda Posadas-Sanchez, Hector Gonzalez-Pacheco, Galileo Escobedo, Betzabe Nieto-Lima, Elizabeth Carreon-Torres and Jose Manuel Fragoso
Biomolecules 2020, 10(10), 1381; https://doi.org/10.3390/biom10101381 - 29 Sep 2020
Cited by 2 | Viewed by 1795
Abstract
Dyslipidemia has a substantial role in the development of acute coronary syndrome (ACS). Low-density lipoprotein receptor (LDLR) plays a critical role in plasma lipoprotein hemostasis, which is involved in the formation of atherosclerotic plaque. This study aimed to evaluate whether LDLR gene polymorphisms [...] Read more.
Dyslipidemia has a substantial role in the development of acute coronary syndrome (ACS). Low-density lipoprotein receptor (LDLR) plays a critical role in plasma lipoprotein hemostasis, which is involved in the formation of atherosclerotic plaque. This study aimed to evaluate whether LDLR gene polymorphisms are significantly associated with ACS and the plasma lipids profile. Three LDLR gene polymorphisms located in the UTR′3 region (c.*52 A/G, c.*504 A/G, and c.* 773 A/G) were determined using TaqMan genotyping assays in a group of 618 ACS patients and 666 healthy controls. Plasma lipids profile concentrations were determined by enzymatic/colorimetric assays. Under co-dominant and recessive models, the c.*52 A allele of the c.*52 A/G polymorphism was associated with a higher risk of ACS (OR = 2.02, pCCo-dom = 0.033, and OR = 2.00, pCRes = 0.009, respectively). In the same way, under co-dominant and recessive models, the c.*773 G allele of the c.*773 A/G polymorphism was associated with a high risk of ACS (OR = 2.04, pCCo-dom = 0.027, and OR = 2.01, pCRes = 0.007, respectively). The “AAG” haplotype was associated with a high risk of ACS (OR = 1.22, pC = 0.016). The c.*52 AA genotype showed a lower HDL-C concentration than individuals with the GG genotype. In addition, carriers of c.*773 GG genotype carriers had a lower concentration of the high-density lipoprotein-cholesterol (HDL-C) than subjects with the AA genotype. Our data suggest the association of the LDLRc.*773 A/G and LDLR c.*52 A/G polymorphisms with both the risk of developing ACS and with a lower concentration of HDL-C in the study population. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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12 pages, 1131 KiB  
Article
Multimarker Approach to Identify Patients with Coronary Artery Disease at High Risk for Subsequent Cardiac Adverse Events: The Multi-Biomarker Study
by Georgiana-Aura Giurgea, Katrin Zlabinger, Alfred Gugerell, Dominika Lukovic, Bonni Syeda, Ljubica Mandic, Noemi Pavo, Julia Mester-Tonczar, Denise Traxler-Weidenauer, Andreas Spannbauer, Nina Kastner, Claudia Müller, Anahit Anvari, Jutta Bergler-Klein and Mariann Gyöngyösi
Biomolecules 2020, 10(6), 909; https://doi.org/10.3390/biom10060909 - 15 Jun 2020
Cited by 3 | Viewed by 2243
Abstract
In our prospective non-randomized, single-center cohort study (n = 161), we have evaluated a multimarker approach including S100 calcium binding protein A12 (S100A1), interleukin 1 like-receptor-4 (IL1R4), adrenomedullin, copeptin, neutrophil gelatinase-associated lipocalin (NGAL), soluble urokinase plasminogen activator receptor (suPAR), and ischemia modified [...] Read more.
In our prospective non-randomized, single-center cohort study (n = 161), we have evaluated a multimarker approach including S100 calcium binding protein A12 (S100A1), interleukin 1 like-receptor-4 (IL1R4), adrenomedullin, copeptin, neutrophil gelatinase-associated lipocalin (NGAL), soluble urokinase plasminogen activator receptor (suPAR), and ischemia modified albumin (IMA) in prediction of subsequent cardiac adverse events (AE) during 1-year follow-up in patients with coronary artery disease. The primary endpoint was to assess the combined discriminatory predictive value of the selected 7 biomarkers in prediction of AE (myocardial infarction, coronary revascularization, death, stroke, and hospitalization) by canonical discriminant function analysis. The main secondary endpoints were the levels of the 7 biomarkers in the groups with/without AE; comparison of the calculated discriminant score of the biomarkers with traditional logistic regression and C-statistics. The canonical correlation coefficient was 0.642, with a Wilk’s lambda value of 0.78 and p < 0.001. By using the calculated discriminant equation with the weighted mean discriminant score (centroid), the sensitivity and specificity of our model were 79.4% and 74.3% in prediction of AE. These values were higher than that of the calculated C-statistics if traditional risk factors with/without biomarkers were used for AE prediction. In conclusion, canonical discriminant analysis of the multimarker approach is able to define the risk threshold at the individual patient level for personalized medicine. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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15 pages, 1682 KiB  
Article
Endothelial Dysfunction May Link Interatrial Septal Abnormalities and MTHFR-Inherited Defects to Cryptogenic Stroke Predisposition
by Luca Sgarra, Alessandro Santo Bortone, Maria Assunta Potenza, Carmela Nacci, Maria Antonietta De Salvia, Tommaso Acquaviva, Emanuela De Cillis, Marco Matteo Ciccone, Massimo Grimaldi and Monica Montagnani
Biomolecules 2020, 10(6), 861; https://doi.org/10.3390/biom10060861 - 04 Jun 2020
Cited by 5 | Viewed by 2290
Abstract
We explored the significance of the L-Arginine/asymmetric dimethylarginine (L-Arg/ADMA) ratio as a biomarker of endothelial dysfunction in stroke patients. To this aim, we evaluated the correlation, in terms of severity, between the degree of endothelial dysfunction (by L-Arg/ADMA ratio), the methylene tetrahydrofolate reductase [...] Read more.
We explored the significance of the L-Arginine/asymmetric dimethylarginine (L-Arg/ADMA) ratio as a biomarker of endothelial dysfunction in stroke patients. To this aim, we evaluated the correlation, in terms of severity, between the degree of endothelial dysfunction (by L-Arg/ADMA ratio), the methylene tetrahydrofolate reductase (MTHFR) genotype, and the interatrial septum (IAS) phenotype in subject with a history of stroke. Methods and Results: L-Arg, ADMA, and MTHFR genotypes were evaluated; the IAS phenotype was assessed by transesophageal echocardiography. Patients were grouped according to the severity of IAS defects and the residual enzymatic activity of MTHFR-mutated variants, and values of L-Arg/ADMA ratio were measured in each subgroup. Of 57 patients, 10 had a septum integrum (SI), 38 a patent foramen ovale (PFO), and 9 an ostium secundum (OS). The L-Arg/ADMA ratio differed across septum phenotypes (p ≤ 0.01), and was higher in SI than in PFO or OS patients (p ≤ 0.05, p ≤ 0.01, respectively). In the PFO subgroup a negative correlation was found between the L-Arg/ADMA ratio and PFO tunnel length/height ratio (p ≤ 0.05; r = − 0.37; R2 = 0.14). Interestingly, the L-Arg/ADMA ratio varied across MTHFR genotypes (p ≤ 0.0001) and was lower in subgroups carrying the most impaired enzyme with respect to patients carrying the conservative MTHFR (p ≤ 0.0001, p ≤ 0.05, respectively). Consistently, OS patients carried the most dysfunctional MTHFR genotypes, whereas SI patients the least ones. Conclusions: A low L-Arg/ADMA ratio correlates with impaired activity of MTHFR and with the jeopardized IAS phenotype along a severity spectrum encompassing OS, PFO with long/tight tunnel, PFO with short/large tunnel, and SI. This infers that genetic MTHFR defects may underlie endothelial dysfunction-related IAS abnormalities, and predispose to a cryptogenic stroke. Our findings emphasize the role of the L-Arg/ADMA ratio as a reliable marker of stroke susceptibility in carriers of IAS abnormalities, and suggest its potential use both as a diagnostic tool and as a decision aid for therapy. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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11 pages, 897 KiB  
Article
The Ser290Asn and Thr715Pro Polymorphisms of the SELP Gene Are Associated with A Lower Risk of Developing Acute Coronary Syndrome and Low Soluble P-Selectin Levels in A Mexican Population
by Gabriel Herrera-Maya, Gilberto Vargas-Alarcón, Oscar Pérez-Méndez, Rosalinda Posadas-Sánchez, Felipe Masso, Teresa Juárez-Cedillo, Galileo Escobedo, Andros Vázquez-Montero and José Manuel Fragoso
Biomolecules 2020, 10(2), 270; https://doi.org/10.3390/biom10020270 - 11 Feb 2020
Cited by 3 | Viewed by 1818
Abstract
Recent studies have shown that P-selectin promotes the early formation of atherosclerotic plaque. The aim of the present study was to evaluate whether the SELP gene single nucleotide polymorphisms (SNPs) are associated with presence of acute coronary syndrome (ACS) and with plasma P-selectin [...] Read more.
Recent studies have shown that P-selectin promotes the early formation of atherosclerotic plaque. The aim of the present study was to evaluate whether the SELP gene single nucleotide polymorphisms (SNPs) are associated with presence of acute coronary syndrome (ACS) and with plasma P-selectin levels in a case-control association study. The sample size was estimated for a statistical power of 80%. We genotyped three SELP (SELP Ser290Asn, SELP Leu599Val, and SELP Thr715Pro) SNPs using 5’ exonuclease TaqMan assays in 625 patients with ACS and 700 healthy controls. The associations were evaluated with logistic regressions under the co-dominant, dominant, recessive, over-dominant and additive inheritance models. The genotype contribution to the plasma P-selectin levels was evaluated by a Student’s t-test. Under different models, the SELP Ser290Asn (OR = 0.59, pCCo-Dominant = 0.047; OR = 0.59, pCDominant = 0.014; OR = 0.58, pCOver-Dominant = 0.061, and OR = 0.62, pCAdditive = 0.015) and SELP Thr715Pro (OR = 0.61, pCDominant = 0.028; OR = 0.63, pCOver-Dominant = 0.044, and OR = 0.62, pCAdditive = 0.023) SNPs were associated with a lower risk of ACS. In addition, these SNPs were associated with low plasma P-selectin levels. In summary, this study established that the SELP Ser290Asn and SELP Thr715Pro SNPs are associated with a lower risk of developing ACS and with decreased P-selectin levels in plasma in a Mexican population. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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13 pages, 947 KiB  
Article
Common Variants in IL-20 Gene are Associated with Subclinical Atherosclerosis, Cardiovascular Risk Factors and IL-20 Levels in the Cohort of the Genetics of Atherosclerotic Disease (GEA) Mexican Study
by Javier Angeles-Martínez, Rosalinda Posadas-Sánchez, Eyerahi Bravo-Flores, María del Carmen González-Salazar and Gilberto Vargas-Alarcón
Biomolecules 2020, 10(1), 75; https://doi.org/10.3390/biom10010075 - 03 Jan 2020
Cited by 5 | Viewed by 2248
Abstract
Inflammation has been involved in the development of atherosclerosis, type 2 diabetes mellitus, insulin resistance, and obesity. Interleukin 20 is a pro-inflammatory cytokine encoded by a polymorphic gene located in chromosome 1. The aim of the study was to evaluate the association of [...] Read more.
Inflammation has been involved in the development of atherosclerosis, type 2 diabetes mellitus, insulin resistance, and obesity. Interleukin 20 is a pro-inflammatory cytokine encoded by a polymorphic gene located in chromosome 1. The aim of the study was to evaluate the association of two IL-20 polymorphisms (rs1400986 and rs1518108) with subclinical atherosclerosis (SA), cardiovascular risk factors and IL-20 levels in a cohort of Mexican individuals. The polymorphisms were determined in 274 individuals with SA and 672 controls. Under different models, rs1400986 (OR = 0.51, Pcodominant1 = 0.0001; OR = 0.36, Pcodominant2 = 0.014; OR = 0.49, Pdominant = 0.0001 and OR = 0.55, Padditive = 0.0001) and rs1518108 (OR = 0.62, Pcodominant2 = 0.048 and OR = 0.79, Padditive = 0.048) were associated with a lower risk of SA. These polymorphisms were associated with cardiovascular risk factors in individuals with SA and controls. Controls with the rs1400986 TT genotype presented high levels of IL-20 (p = 0.031). In individuals with the rs1400986 CC genotype, we observed a negative correlation between IL-20 levels and total abdominal tissue (TAT), visceral abdominal tissue (VAT) and subcutaneous abdominal tissue (SAT). Our results indicate that the IL-20 rs1400986 and rs1518108 polymorphisms were associated with decreased risk of developing SA and with some cardiovascular risk factors in individuals with SA and healthy controls. Negative correlation between BMI and VAT/SAT ratio in individuals with rs1400986 CC genotype and among IL-20 levels and TAT, VAT and SAT was observed. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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22 pages, 9309 KiB  
Article
Analysis of Differentially Expressed Genes in Coronary Artery Disease by Integrated Microarray Analysis
by Meenashi Vanathi Balashanmugam, Thippeswamy Boreddy Shivanandappa, Sivagurunathan Nagarethinam, Basavaraj Vastrad and Chanabasayya Vastrad
Biomolecules 2020, 10(1), 35; https://doi.org/10.3390/biom10010035 - 25 Dec 2019
Cited by 13 | Viewed by 5288
Abstract
Coronary artery disease (CAD) is a major cause of end-stage cardiac disease. Although profound efforts have been made to illuminate the pathogenesis, the molecular mechanisms of CAD remain to be analyzed. To identify the candidate genes in the advancement of CAD, microarray dataset [...] Read more.
Coronary artery disease (CAD) is a major cause of end-stage cardiac disease. Although profound efforts have been made to illuminate the pathogenesis, the molecular mechanisms of CAD remain to be analyzed. To identify the candidate genes in the advancement of CAD, microarray dataset GSE23766 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified, and pathway and gene ontology (GO) enrichment analyses were performed. The protein-protein interaction network was constructed and the module analysis was performed using the Biological General Repository for Interaction Datasets (BioGRID) and Cytoscape. Additionally, target genes-miRNA regulatory network and target genes-TF regulatory network were constructed and analyzed. There were 894 DEGs between male human CAD samples and female human CAD samples, including 456 up regulated genes and 438 down regulated genes. Pathway enrichment analyses revealed that DEGs (up and down regulated) were mostly enriched in the superpathway of steroid hormone biosynthesis, ABC transporters, oxidative ethanol degradation III and Complement and coagulation cascades. Similarly, geneontology enrichment analyses revealed that DEGs (up and down regulated) were mostly enriched in the forebrain neuron differentiation, filopodium membrane, platelet degranulation and blood microparticle. In the PPI network and modules (up and down regulated), MYC, NPM1, TRPC7, UBC, FN1, HEMK1, IFT74 and VHL were hub genes. In the target genes-miRNA regulatory network and target genes—TF regulatory network (up and down regulated), TAOK1, KHSRP, HSD17B11 and PAH were target genes. In conclusion, the pathway and GO ontology enriched by DEGs may reveal the molecular mechanism of CAD. Its hub and target genes, MYC, NPM1, TRPC7, UBC, FN1, HEMK1, IFT74, VHL, TAOK1, KHSRP, HSD17B11 and PAH were expected to be new targets for CAD. Our finding provided clues for exploring molecular mechanism and developing new prognostics, diagnostic and therapeutic strategies for CAD. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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Review

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17 pages, 768 KiB  
Review
A Changing Paradigm in Heart Transplantation: An Integrative Approach for Invasive and Non-Invasive Allograft Rejection Monitoring
by Alessia Giarraputo, Ilaria Barison, Marny Fedrigo, Jacopo Burrello, Chiara Castellani, Francesco Tona, Tomaso Bottio, Gino Gerosa, Lucio Barile and Annalisa Angelini
Biomolecules 2021, 11(2), 201; https://doi.org/10.3390/biom11020201 - 01 Feb 2021
Cited by 13 | Viewed by 5514
Abstract
Cardiac allograft rejection following heart transplantation is challenging to diagnose. Tissue biopsies are the gold standard in monitoring the different types of rejection. The last decade has seen an increased emphasis on identifying non-invasive methods to improve rejection diagnosis and overcome tissue biopsy [...] Read more.
Cardiac allograft rejection following heart transplantation is challenging to diagnose. Tissue biopsies are the gold standard in monitoring the different types of rejection. The last decade has seen an increased emphasis on identifying non-invasive methods to improve rejection diagnosis and overcome tissue biopsy invasiveness. Liquid biopsy, as an efficient non-invasive diagnostic and prognostic oncological monitoring tool, seems to be applicable in heart transplant follow-ups. Moreover, molecular techniques applied on blood can be translated to tissue samples to provide novel perspectives on tissue and reveal new diagnostic and prognostic biomarkers. This review aims to provide a comprehensive overview of the state-of-the-art of the new methodologies in cardiac allograft rejection monitoring and investigate the future perspectives on invasive and non-invasive rejection biomarkers identification. We reviewed literature from the most used scientific databases, such as PubMed, Google Scholar, and Scopus. We extracted 192 papers and, after a selection and exclusion process, we included in the review 81 papers. The described limitations notwithstanding, this review show how molecular biology techniques and omics science could be deployed complementarily to the histopathological rejection diagnosis on tissue biopsies, thus representing an integrated approach for heart transplant patients monitoring. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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10 pages, 758 KiB  
Review
Galectin-3 and sST2 as Prognosticators for Heart Failure Requiring Extracorporeal Life Support: Jack n’ Jill
by Jianli Bi, Vidu Garg and Andrew R. Yates
Biomolecules 2021, 11(2), 166; https://doi.org/10.3390/biom11020166 - 27 Jan 2021
Cited by 6 | Viewed by 2414
Abstract
Extracorporeal life support provides perfusion for patients with heart failure to allow time for recovery, function as a bridge for patients to heart transplantation, or serve as destination therapy for long term mechanical device support. Several biomarkers have been employed in attempt to [...] Read more.
Extracorporeal life support provides perfusion for patients with heart failure to allow time for recovery, function as a bridge for patients to heart transplantation, or serve as destination therapy for long term mechanical device support. Several biomarkers have been employed in attempt to predict these outcomes, but it remains to be determined which are suitable to guide clinical practice relevant to extracorporeal life support. Galectin-3 and soluble suppression of tumorigenicity-2 (sST2) are two of the more promising candidates with the greatest supporting evidence. In this review, we address the similarities and differences between galectin-3 and sST2 for prognostic prediction in adults and children with heart failure requiring extracorporeal life support and highlight the significant lack of progress in pediatric biomarker discovery and utilization. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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22 pages, 798 KiB  
Review
Post-Myocardial Infarction Ventricular Remodeling Biomarkers—The Key Link between Pathophysiology and Clinic
by Maria-Madălina Bostan, Cristian Stătescu, Larisa Anghel, Ionela-Lăcrămioara Șerban, Elena Cojocaru and Radu Sascău
Biomolecules 2020, 10(11), 1587; https://doi.org/10.3390/biom10111587 - 23 Nov 2020
Cited by 25 | Viewed by 6080
Abstract
Studies in recent years have shown increased interest in developing new methods of evaluation, but also in limiting post infarction ventricular remodeling, hoping to improve ventricular function and the further evolution of the patient. This is the point where biomarkers have proven effective [...] Read more.
Studies in recent years have shown increased interest in developing new methods of evaluation, but also in limiting post infarction ventricular remodeling, hoping to improve ventricular function and the further evolution of the patient. This is the point where biomarkers have proven effective in early detection of remodeling phenomena. There are six main processes that promote the remodeling and each of them has specific biomarkers that can be used in predicting the evolution (myocardial necrosis, neurohormonal activation, inflammatory reaction, hypertrophy and fibrosis, apoptosis, mixed processes). Some of the biomarkers such as creatine kinase–myocardial band (CK-MB), troponin, and N-terminal-pro type B natriuretic peptide (NT-proBNP) were so convincing that they immediately found their place in the post infarction patient evaluation protocol. Others that are related to more complex processes such as inflammatory biomarkers, atheroma plaque destabilization biomarkers, and microRNA are still being studied, but the results so far are promising. This article aims to review the markers used so far, but also the existing data on new markers that could be considered, taking into consideration the most important studies that have been conducted so far. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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21 pages, 1429 KiB  
Review
Circulating microRNA as a Biomarker for Coronary Artery Disease
by Ibrahim T. Fazmin, Zakaria Achercouk, Charlotte E. Edling, Asri Said and Kamalan Jeevaratnam
Biomolecules 2020, 10(10), 1354; https://doi.org/10.3390/biom10101354 - 23 Sep 2020
Cited by 20 | Viewed by 3772
Abstract
Coronary artery disease (CAD) is the leading cause of sudden cardiac death in adults, and new methods of predicting disease and risk-stratifying patients will help guide intervention in order to reduce this burden. Current CAD detection involves multiple modalities, but the consideration of [...] Read more.
Coronary artery disease (CAD) is the leading cause of sudden cardiac death in adults, and new methods of predicting disease and risk-stratifying patients will help guide intervention in order to reduce this burden. Current CAD detection involves multiple modalities, but the consideration of other biomarkers will help improve reliability. The aim of this narrative review is to help researchers and clinicians appreciate the growing relevance of miRNA in CAD and its potential as a biomarker, and also to suggest useful miRNA that may be targets for future study. We sourced information from several databases, namely PubMed, Scopus, and Google Scholar, when collating evidentiary information. MicroRNAs (miRNA) are short, noncoding RNAs that are relevant in cardiovascular physiology and pathophysiology, playing roles in cardiac hypertrophy, maintenance of vascular tone, and responses to vascular injury. CAD is associated with changes in miRNA expression profiles, and so are its risk factors, such as abnormal lipid metabolism and inflammation. Thus, they may potentially be biomarkers of CAD. Nevertheless, there are limitations in using miRNA. These include cost and the presence of several confounding factors that may affect miRNA profiles. Furthermore, there is difficulty in the normalisation of miRNA values between published studies, due to pre-analytical variations in samples. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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18 pages, 2442 KiB  
Review
Galectin-3: A Potential Prognostic and Diagnostic Marker for Heart Disease and Detection of Early Stage Pathology
by Akira Hara, Masayuki Niwa, Tomohiro Kanayama, Kei Noguchi, Ayumi Niwa, Mikiko Matsuo, Takahiro Kuroda, Yuichiro Hatano, Hideshi Okada and Hiroyuki Tomita
Biomolecules 2020, 10(9), 1277; https://doi.org/10.3390/biom10091277 - 04 Sep 2020
Cited by 37 | Viewed by 4845
Abstract
The use of molecular biomarkers for the early detection of heart disease, before their onset of symptoms, is an attractive novel approach. Ideal molecular biomarkers, those that are both sensitive and specific to heart disease, are likely to provide a much earlier diagnosis, [...] Read more.
The use of molecular biomarkers for the early detection of heart disease, before their onset of symptoms, is an attractive novel approach. Ideal molecular biomarkers, those that are both sensitive and specific to heart disease, are likely to provide a much earlier diagnosis, thereby providing better treatment outcomes. Galectin-3 is expressed by various immune cells, including mast cells, histiocytes and macrophages, and plays an important role in diverse physiological functions. Since galectin-3 is readily expressed on the cell surface, and is readily secreted by injured and inflammatory cells, it has been suggested that cardiac galectin-3 could be a marker for cardiac disorders such as cardiac inflammation and fibrosis, depending on the specific pathogenesis. Thus, galectin-3 may be a novel candidate biomarker for the diagnosis, analysis and prognosis of various cardiac diseases, including heart failure. The goals of heart disease treatment are to prevent acute onset and to predict their occurrence by using the ideal molecular biomarkers. In this review, we discuss and summarize recent developments of galectin-3 as a next-generation molecular biomarker of heart disease. Furthermore, we describe how galectin-3 may be useful as a diagnostic marker for detecting the early stages of various heart diseases, which may contribute to improved early therapeutic interventions. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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15 pages, 1129 KiB  
Review
Sarcomeric Gene Variants and Their Role with Left Ventricular Dysfunction in Background of Coronary Artery Disease
by Surendra Kumar, Vijay Kumar and Jong-Joo Kim
Biomolecules 2020, 10(3), 442; https://doi.org/10.3390/biom10030442 - 12 Mar 2020
Cited by 3 | Viewed by 3003
Abstract
Cardiovascular diseases are one of the leading causes of death in developing countries, generally originating as coronary artery disease (CAD) or hypertension. In later stages, many CAD patients develop left ventricle dysfunction (LVD). Left ventricular ejection fraction (LVEF) is the most prevalent prognostic [...] Read more.
Cardiovascular diseases are one of the leading causes of death in developing countries, generally originating as coronary artery disease (CAD) or hypertension. In later stages, many CAD patients develop left ventricle dysfunction (LVD). Left ventricular ejection fraction (LVEF) is the most prevalent prognostic factor in CAD patients. LVD is a complex multifactorial condition in which the left ventricle of the heart becomes functionally impaired. Various genetic studies have correlated LVD with dilated cardiomyopathy (DCM). In recent years, enormous progress has been made in identifying the genetic causes of cardiac diseases, which has further led to a greater understanding of molecular mechanisms underlying each disease. This progress has increased the probability of establishing a specific genetic diagnosis, and thus providing new opportunities for practitioners, patients, and families to utilize this genetic information. A large number of mutations in sarcomeric genes have been discovered in cardiomyopathies. In this review, we will explore the role of the sarcomeric genes in LVD in CAD patients, which is a major cause of cardiac failure and results in heart failure. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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18 pages, 339 KiB  
Review
The Role of Secretory Activity Molecules of Visceral Adipocytes in Abdominal Obesity in the Development of Cardiovascular Disease: A Review
by Yuliya I. Ragino, Ekaterina M. Stakhneva, Yana V. Polonskaya and Elena V. Kashtanova
Biomolecules 2020, 10(3), 374; https://doi.org/10.3390/biom10030374 - 28 Feb 2020
Cited by 36 | Viewed by 3864
Abstract
Adipose tissue is considered one of the endocrine organs in the body because of its ability to synthesize and release a large number of hormones, cytokines, and growth and vasoactive factors that influence a variety of physiological and pathophysiological processes, such as vascular [...] Read more.
Adipose tissue is considered one of the endocrine organs in the body because of its ability to synthesize and release a large number of hormones, cytokines, and growth and vasoactive factors that influence a variety of physiological and pathophysiological processes, such as vascular tone, inflammation, vascular smooth muscle cell migration, endothelial function, and vascular redox state. Moreover, genetic factors substantially contribute to the risk of obesity. Research into the biochemical effects of molecules secreted by visceral adipocytes as well as their molecular genetic characteristics is actively conducted around the world mostly in relation to pathologies of the cardiovascular system, metabolic syndrome, and diabetes mellitus. Adipokines could be developed into biomarkers for diagnosis, prognosis, and therapeutic targets in different diseases. This review describes the relevance of secretory activity molecules of visceral adipocytes in cardiovascular disease associated abdominal obesity. Full article
(This article belongs to the Special Issue Molecular Biomarkers In Cardiology)
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