Editorial

4 pages, 186 KiB

Open AccessEditorial

Emerging New Biomarkers for Cardiovascular Disease

by Luc Rochette

Int. J. Mol. Sci. 2022, 23(6), 3274; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063274 - 18 Mar 2022

Cited by 3 | Viewed by 1698

In this Special Issue of the International Journal of Molecular Sciences, we include insightful reviews and research papers on the subject “Emerging New Biomarkers for Cardiovascular Disease” [...] Full article

(This article belongs to the Special Issue Emerging New Biomarkers for Cardiovascular Disease)

Research

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15 pages, 1904 KiB

Open AccessArticle

Identification of Exosomal MicroRNA Signature by Liquid Biopsy in Hereditary Hemorrhagic Telangiectasia Patients

by Ana Pozo-Agundo, Nerea Villaescusa, Jordi Martorell-Marugán, Olga Soriano, Socorro Leyva, Ana Belén Jódar-Reyes, Luisa María Botella, Pedro Carmona-Sáez and Francisco Javier Blanco

Int. J. Mol. Sci. 2021, 22(17), 9450; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179450 - 31 Aug 2021

Cited by 3 | Viewed by 2383

Abstract

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant vascular dysplasia characterized by epistaxis, mucocutaneous telangiectases, and arteriovenous malformations (AVM) in the visceral organs. The diagnosis of HHT is based on clinical Curaçao criteria, which show limited sensitivity in children and young patients. [...] Read more.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant vascular dysplasia characterized by epistaxis, mucocutaneous telangiectases, and arteriovenous malformations (AVM) in the visceral organs. The diagnosis of HHT is based on clinical Curaçao criteria, which show limited sensitivity in children and young patients. Here, we carried out a liquid biopsy by which we isolated total RNA from plasma exosome samples. A cohort of 15 HHT type 1 patients, 15 HHT type 2 patients, and 10 healthy relatives were analyzed. Upon gene expression data processing and normalization, a statistical analysis was performed to explore similarities in microRNA expression patterns among samples and detect differentially expressed microRNAs between HHT samples and the control group. We found a disease-associated molecular fingerprint of 35 miRNAs over-represented in HHT vs. controls, with eight being specific for HHT1 and 11 for HHT2; we also found 30 under-represented, including nine distinct for HHT1 and nine for HHT2. The analysis of the receiver operating characteristic (ROC) curves showed that eight miRNAs had good (AUC > 75%) or excellent (AUC > 90%) diagnosis value for HHT and even for type HHT1 and HHT2. In addition, we identified the cellular origin of these miRNAs among the cell types involved in the vascular malformations. Interestingly, we found that only some of them were incorporated into exosomes, which suggests a key functional role of these exosomal miRNAs in the pathophysiology of HHT. Full article

(This article belongs to the Special Issue Emerging New Biomarkers for Cardiovascular Disease)

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11 pages, 496 KiB

Open AccessArticle

Urinary Levels of the Acrolein Conjugates of Carnosine Are Associated with Cardiovascular Disease Risk

by Timothy E. O’Toole, Xiaohong Li, Daniel W. Riggs, David J. Hoetker, Shahid P. Baba and Aruni Bhatnagar

Int. J. Mol. Sci. 2021, 22(3), 1383; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031383 - 30 Jan 2021

Cited by 5 | Viewed by 2152

Abstract

Carnosine is a naturally occurring dipeptide (β-alanine-L-histidine) which supports physiological homeostasis by buffering intracellular pH, chelating metals, and conjugating with and neutralizing toxic aldehydes such as acrolein. However, it is not clear if carnosine can support cardiovascular function or modify cardiovascular disease (CVD) [...] Read more.

Carnosine is a naturally occurring dipeptide (β-alanine-L-histidine) which supports physiological homeostasis by buffering intracellular pH, chelating metals, and conjugating with and neutralizing toxic aldehydes such as acrolein. However, it is not clear if carnosine can support cardiovascular function or modify cardiovascular disease (CVD) risk. To examine this, we measured urinary levels of nonconjugated carnosine and its acrolein conjugates (carnosine-propanal and carnosine-propanol) in participants of the Louisville Healthy Heart Study and examined associations with indices of CVD risk. We found that nonconjugated carnosine was significantly associated with hypertension (p = 0.011), heart failure (p = 0.015), those categorized with high CVD risk (p < 0.001), body mass index (BMI; p = 0.007), high sensitivity C-reactive protein (hsCRP; p = 0.026), high-density lipoprotein (HDL; p = 0.007) and certain medication uses. Levels of carnosine-propanal and carnosine-propanol demonstrated significant associations with BMI, blood glucose, HDL and diagnosis of diabetes. Carnosine-propanal was also associated with heart failure (p = 0.045) and hyperlipidemia (p = 0.002), but no associations with myocardial infarction or stroke were identified. We found that the positive associations of carnosine conjugates with diabetes and HDL remain statistically significant (p < 0.05) in an adjusted, linear regression model. These findings suggest that urinary levels of nonconjugated carnosine, carnosine-propanal and carnosine-propanol may be informative biomarkers for the assessment of CVD risk—and particularly reflective of skeletal muscle injury and carnosine depletion in diabetes. Full article

(This article belongs to the Special Issue Emerging New Biomarkers for Cardiovascular Disease)

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11 pages, 658 KiB

Open AccessArticle

Determinants of Increased Serum Calprotectin in Patients with Type 2 Diabetes Mellitus

by Milou M. Oosterwijk, Stephan J.L. Bakker, Tom Nilsen, Gerjan Navis and Gozewijn D. Laverman

Int. J. Mol. Sci. 2020, 21(21), 8075; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218075 - 29 Oct 2020

Cited by 11 | Viewed by 2140

Abstract

Circulating calprotectin is a potential biomarker for endovascular inflammation in type 2 diabetes mellitus (T2DM). We investigated the determinants of calprotectin and its relationship with the presence of cardiovascular disease (CVD) in 362 T2DM patients included in the Diabetes and Lifestyle Cohort Twente-1 [...] Read more.

Circulating calprotectin is a potential biomarker for endovascular inflammation in type 2 diabetes mellitus (T2DM). We investigated the determinants of calprotectin and its relationship with the presence of cardiovascular disease (CVD) in 362 T2DM patients included in the Diabetes and Lifestyle Cohort Twente-1 (DIALECT-1) study. Lifestyle exposures, including nutrition, were determined by validated questionnaires. CVD was defined as coronary artery diseases, strokes, and peripheral artery diseases. Median serum calprotectin levels were 1.04 mg/L [IQR: 0.73–1.46 mg/L] and were higher in women (1.11 mg/L) than men (0.96 mg/L, p = 0.007). Current smoking was a major independent determinant of circulating calprotectin, with a 51% higher calprotectin compared to never smoking (p < 0.001). Albuminuria (p = 0.011), former smoking (p = 0.023), and intake of mono- and disaccharides (p = 0.005) also contributed independently to circulating calprotectin. Each incremental increase in calprotectin level was associated with 1.36-times higher odds for CVD (95% CI 1.04–1.77, p = 0.026). In the current study, calprotectin was the only inflammatory parameter significantly associated with CVD. The strong association of circulating calprotectin with smoking, a well-known direct cause of vascular inflammation, and also with CVD, stresses the urge for further research to define its role as a biomarker in T2DM. Full article

(This article belongs to the Special Issue Emerging New Biomarkers for Cardiovascular Disease)

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Review

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16 pages, 984 KiB

Open AccessReview

Traditional and Emerging Biomarkers in Asymptomatic Left Ventricular Dysfunction—Promising Non-Coding RNAs and Exosomes as Biomarkers in Early Phases of Cardiac Damage

by Milijana Janjusevic, Alessandra Lucia Fluca, Federico Ferro, Giulia Gagno, Yuri D’Alessandra, Antonio Paolo Beltrami, Gianfranco Sinagra and Aneta Aleksova

Int. J. Mol. Sci. 2021, 22(9), 4937; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094937 - 06 May 2021

Cited by 11 | Viewed by 3886

Abstract

Heart failure (HF) is one of the major causes of morbidity and mortality worldwide and represents an escalating problem for healthcare systems. The identification of asymptomatic patients with underlying cardiac subclinical disease would create an opportunity for early intervention and prevention of symptomatic [...] Read more.

Heart failure (HF) is one of the major causes of morbidity and mortality worldwide and represents an escalating problem for healthcare systems. The identification of asymptomatic patients with underlying cardiac subclinical disease would create an opportunity for early intervention and prevention of symptomatic HF. Traditional biomarkers are very useful as diagnostic and prognostic tools in the cardiovascular field; however, their application is usually limited to overt cardiac disease. On the other hand, a growing number of studies is investigating the diagnostic and prognostic potential of new biomarkers, such as micro-RNAs (miRNA), long non-coding RNAs, and exosome cargo, because of their involvement in the early phases of cardiac dysfunction. Unfortunately, their use in asymptomatic phases remains a distant goal. The aim of this review is to gather the current knowledge of old and novel biomarkers in the early diagnosis of cardiac dysfunction in asymptomatic individuals. Full article

(This article belongs to the Special Issue Emerging New Biomarkers for Cardiovascular Disease)

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24 pages, 3350 KiB

Open AccessReview

The Time Has Come to Explore Plasma Biomarkers in Genetic Cardiomyopathies

by Nienke M. Stege, Rudolf A. de Boer, Maarten P. van den Berg and Herman H. W. Silljé

Int. J. Mol. Sci. 2021, 22(6), 2955; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22062955 - 14 Mar 2021

Cited by 11 | Viewed by 3825

Abstract

For patients with hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM), screening for pathogenic variants has become standard clinical practice. Genetic cascade screening also allows the identification of relatives that carry the same mutation as the proband, but disease onset and [...] Read more.

For patients with hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM), screening for pathogenic variants has become standard clinical practice. Genetic cascade screening also allows the identification of relatives that carry the same mutation as the proband, but disease onset and severity in mutation carriers often remains uncertain. Early detection of disease onset may allow timely treatment before irreversible changes are present. Although plasma biomarkers may aid in the prediction of disease onset, monitoring relies predominantly on identifying early clinical symptoms, on imaging techniques like echocardiography (Echo) and cardiac magnetic resonance imaging (CMR), and on (ambulatory) electrocardiography (electrocardiograms (ECGs)). In contrast to most other cardiac diseases, which are explained by a combination of risk factors and comorbidities, genetic cardiomyopathies have a clear primary genetically defined cardiac background. Cardiomyopathy cohorts could therefore have excellent value in biomarker studies and in distinguishing biomarkers related to the primary cardiac disease from those related to extracardiac, secondary organ dysfunction. Despite this advantage, biomarker investigations in cardiomyopathies are still limited, most likely due to the limited number of carriers in the past. Here, we discuss not only the potential use of established plasma biomarkers, including natriuretic peptides and troponins, but also the use of novel biomarkers, such as cardiac autoantibodies in genetic cardiomyopathy, and discuss how we can gauge biomarker studies in cardiomyopathy cohorts for heart failure at large. Full article

(This article belongs to the Special Issue Emerging New Biomarkers for Cardiovascular Disease)

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17 pages, 579 KiB

Open AccessReview

Cardiac T-Tubule cBIN1-Microdomain, a Diagnostic Marker and Therapeutic Target of Heart Failure

by Jing Li, Bradley Richmond and TingTing Hong

Int. J. Mol. Sci. 2021, 22(5), 2299; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052299 - 25 Feb 2021

Cited by 4 | Viewed by 2962

Abstract

Since its first identification as a cardiac transverse tubule (t-tubule) protein, followed by the cloning of the cardiac isoform responsible for t-tubule membrane microdomain formation, cardiac bridging integrator 1 (cBIN1) and its organized microdomains have emerged as a key mechanism in maintaining normal [...] Read more.

Since its first identification as a cardiac transverse tubule (t-tubule) protein, followed by the cloning of the cardiac isoform responsible for t-tubule membrane microdomain formation, cardiac bridging integrator 1 (cBIN1) and its organized microdomains have emerged as a key mechanism in maintaining normal beat-to-beat heart contraction and relaxation. The abnormal remodeling of cBIN1-microdomains occurs in stressed and diseased cardiomyocytes, contributing to the pathophysiology of heart failure. Due to the homeostatic turnover of t-tubule cBIN1-microdomains via microvesicle release into the peripheral circulation, plasma cBIN1 can be assayed as a liquid biopsy of cardiomyocyte health. A new blood test cBIN1 score (CS) has been developed as a dimensionless inverse index derived from plasma cBIN1 concentration with a diagnostic and prognostic power for clinical outcomes in stable ambulatory patients with heart failure with reduced or preserved ejection fraction (HFrEF or HFpEF). Recent evidence further indicates that exogenous cBIN1 introduced by adeno-associated virus 9-based gene therapy can rescue cardiac contraction and relaxation in failing hearts. The therapeutic potential of cBIN1 gene therapy is enormous given its ability to rescue cardiac inotropy and provide lusitropic protection in the meantime. These unprecedented capabilities of cBIN1 gene therapy are shifting the current paradigm of therapy development for heart failure, particularly HFpEF. Full article

(This article belongs to the Special Issue Emerging New Biomarkers for Cardiovascular Disease)

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25 pages, 1213 KiB

Open AccessReview

The Emerging Role of TXNIP in Ischemic and Cardiovascular Diseases; A Novel Marker and Therapeutic Target

by Alison Domingues, Julia Jolibois, Perrine Marquet de Rougé and Valérie Nivet-Antoine

Int. J. Mol. Sci. 2021, 22(4), 1693; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041693 - 08 Feb 2021

Cited by 31 | Viewed by 4717

Abstract

Thioredoxin interacting protein (TXNIP) is a metabolism- oxidative- and inflammation-related marker induced in cardiovascular diseases and is believed to represent a possible link between metabolism and cellular redox status. TXNIP is a potential biomarker in cardiovascular and ischemic diseases but also a novel [...] Read more.

Thioredoxin interacting protein (TXNIP) is a metabolism- oxidative- and inflammation-related marker induced in cardiovascular diseases and is believed to represent a possible link between metabolism and cellular redox status. TXNIP is a potential biomarker in cardiovascular and ischemic diseases but also a novel identified target for preventive and curative medicine. The goal of this review is to focus on the novelties concerning TXNIP. After an overview in TXNIP involvement in oxidative stress, inflammation and metabolism, the remainder of this review presents the clues used to define TXNIP as a new marker at the genetic, blood, or ischemic site level in the context of cardiovascular and ischemic diseases. Full article

(This article belongs to the Special Issue Emerging New Biomarkers for Cardiovascular Disease)

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