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Biomedicines
Special Issues
Advances in Biomarker Discovery for Cardiovascular Disease
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Advances in Biomarker Discovery for Cardiovascular Disease

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 3520

Special Issue Editors

Dr. Qin Fu

E-Mail Website
Guest Editor
Proteomics and Metabolomics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY 14850, USA
Interests: proteomics; biomarkers; diseases diagnostic and therapy; pharmacokinetics
Dr. Haijun Liu

E-Mail Website
Guest Editor
Transplantation Research Center (TRC), Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
Interests: nanomedicine; drug delivery; biomaterials

Special Issue Information

Dear Colleagues,

Cardiovascular disease, a disorder affecting the heart and blood vessels, is one of the leading causes of death worldwide. It includes coronary heart disease, cerebrovascular disease, rheumatic heart disease, and other conditions, causing an estimated 17.9 million deaths annually. Addressing the early detection and eventual treatment of this noncommunicable disease is crucial for maintaining public health. Multiomics, including genomics, transcriptomics, proteomics, metabolomics, etc., for biomarker discovery are unequivocally powerful tools for elucidating the molecular mechanisms underlying cardiovascular disease, which helps to unravel novel diagnostic and therapeutic biomarker candidates. Sequencing-based genomics and transcriptomics, as well as mass-spectroscopy-based proteomics and metabolomic technologies, enable the unprecedented large-scale identification and quantification of DNAs, RNAs, proteins, peptides, post-translational modifications, and metabolites, providing critical insights into cardiovascular pathophysiology. This Special Issue will focus on the latest advancements in biomarker discovery for cardiovascular disease, aiming to establish earlier detection and therapy strategies.

We cordially invite authors working on this complex and promising field to submit their original research, communications, and review articles to Biomedicines. Topics of interest include, but are not limited to, the following:

  • Genomics and transcriptomics studies in cardiovascular disease;
  • Proteome and peptidome analysis in cardiovascular disease;
  • Post-translational modification studies in cardiovascular disease;
  • Metabolomics studies in cardiovascular disease;
  • Novel biomarkers discovery in cardiovascular disease;
  • Identification of therapeutic targets for cardiovascular disease;
  • Mass-spectrometry-based proteomics for heart and blood vessels pathophysiology;
  • Development of medicines for cardiovascular disease.

Dr. Qin Fu
Dr. Haijun Liu
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cardiovascular disease
  • genomics
  • transcriptomics
  • proteomics
  • metabolomics
  • multiomics
  • gene sequencing
  • liquid chromatography/gas chromatography tandem mass spectrometry
  • diagnostic biomarkers
  • biomedicine

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (4 papers)

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Research

16 pages, 820 KiB  
Article
Kynurenine as a Predictor of Long-Term Mortality: A 10-Year Follow-Up from the KORONEF Registry
by Adam Kern, Tomasz Stompór, Krystian Bojko, Ewa Sienkiewicz, Sebastian Pawlak, Krystyna Pawlak, Dariusz Pawlak, Grzegorz Poskrobko, Ewa Andrasz, Leszek Gromadziński, Rakesh Jalali, Dariusz Onichimowski, Grażyna Piwko, Artur Zalewski and Jacek Bil
Biomedicines 2025, 13(5), 1123; https://doi.org/10.3390/biomedicines13051123 - 6 May 2025
Viewed by 184
Abstract
Background: The kynurenine (KYN) pathway of tryptophan metabolism has been linked to inflammation and cardiovascular risk, but its long-term prognostic value remains unclear. Methods: We analyzed 492 patients from the KORONEF registry who underwent coronary and renal angiography and were followed [...] Read more.
Background: The kynurenine (KYN) pathway of tryptophan metabolism has been linked to inflammation and cardiovascular risk, but its long-term prognostic value remains unclear. Methods: We analyzed 492 patients from the KORONEF registry who underwent coronary and renal angiography and were followed for a median of 10.2 years. Plasma levels of tryptophan (TRP), KYN, and downstream metabolites were measured. The primary endpoint was all-cause mortality. Results: The mean age was 64.4 ± 9.9 years, and 37.2% of patients were female. Common comorbidities included hypertension (74.8%), dyslipidemia (46.0%), and diabetes (25.8%). Overall mortality reached 29.5% and increased across KYN tertiles: 17.6% (T1), 28.2% (T2), and 42.9% (T3) (p < 0.001). In a multivariable Cox analysis, KYN independently predicted mortality (HR: 1.79; 95% CI: 1.15–2.44; p < 0.001), alongside age, diabetes, prior myocardial infarction, chronic kidney disease, and left ventricular ejection fraction. Other kynurenine pathway metabolites were not independently associated with outcomes. Conclusions: Elevated kynurenine levels independently predict 10-year all-cause mortality in patients undergoing coronary angiography. KYN may represent a useful prognostic biomarker beyond traditional clinical and angiographic variables. Full article
(This article belongs to the Special Issue Advances in Biomarker Discovery for Cardiovascular Disease)
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12 pages, 517 KiB  
Article
Donor-Derived Cell-Free DNA Versus Left Ventricular Longitudinal Strain and Strain-Derived Myocardial Work Indices for Identification of Heart Transplant Injury
by Timea Teszak, Timea Barcziova, Csaba Bödör, Lajos Hegyi, Luca Levay, Beata Nagy, Attila Fintha, Adam Szijarto, Attila Kovacs, Bela Merkely and Balazs Sax
Biomedicines 2025, 13(4), 841; https://doi.org/10.3390/biomedicines13040841 - 1 Apr 2025
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Abstract
Background/Objectives: Donor-derived cell-free DNA (dd-cfDNA) is a marker of graft injury that increases in acute rejection and has excellent negative predictive value. Left ventricular global longitudinal strain (LVGLS) and strain-derived myocardial work indices are novel echocardiographic parameters with growing applications. Still, they have [...] Read more.
Background/Objectives: Donor-derived cell-free DNA (dd-cfDNA) is a marker of graft injury that increases in acute rejection and has excellent negative predictive value. Left ventricular global longitudinal strain (LVGLS) and strain-derived myocardial work indices are novel echocardiographic parameters with growing applications. Still, they have been poorly investigated in heart transplant (HTx) recipients so far. We sought to examine the diagnostic impact of left ventricular longitudinal strain-derived indices in diagnosing myocardial injury as assessed by dd-cfDNA after HTx. Methods: Since October 2022, HTx recipients have been shifted from our endomyocardial biopsy (EMB)-based rejection surveillance protocol to a monthly dd-cfDNA-led rejection assessment. We analysed the percentage of donor-derived to total cell-free DNA. For echocardiographic analysis, patient selection was restricted to those transplanted ≥ 6 months. We used 2D speckle-tracking echocardiography to assess LVGLS and strain-derived myocardial work parameters. Results: We analysed four hundred and forty-nine dd-cfDNA samples from seventy-one patients until November 2024. The mean dd-cfDNA fraction remained very low (0.13 ± 0.06%). Eighty-eight percent of surveillance EMBs that would have otherwise been performed were avoided. The mean LVGLS was lower than the literature reference values. We found no correlation between dd-cfDNA and LVGLS. Transplanted hearts had different myocardial work indices than the reference values reported in the literature. Conclusions: dd-cfDNA effectively rules out clinically significant acute rejection and decreases the need for invasive surveillance EMBs. LVGLS seems less sensitive than dd-cfDNA for the identification of myocardial injury in the early stages of HTx rejection in patients at low risk for rejection. Full article
(This article belongs to the Special Issue Advances in Biomarker Discovery for Cardiovascular Disease)
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20 pages, 2893 KiB  
Article
Early Myocardial Strain Reduction and miR-122-5p Elevation Associated with Interstitial Fibrosis in Anthracycline-Induced Cardiotoxicity
by María de Regla Caballero-Valderrama, Elisa Bevilacqua, Miriam Echevarría, Francisco Javier Salvador-Bofill, Antonio Ordóñez, José Eduardo López-Haldón, Tarik Smani and Eva M. Calderón-Sánchez
Biomedicines 2025, 13(1), 45; https://doi.org/10.3390/biomedicines13010045 - 27 Dec 2024
Viewed by 1020
Abstract
Echocardiographic myocardial strain is crucial for early detection of anthracycline-induced cardiotoxicity, particularly in patients at moderate or high risk. Background/Objectives: This study investigates changes in global longitudinal strain (GLS) in breast cancer patients with low baseline risk for cardiotoxicity during cancer therapy. We [...] Read more.
Echocardiographic myocardial strain is crucial for early detection of anthracycline-induced cardiotoxicity, particularly in patients at moderate or high risk. Background/Objectives: This study investigates changes in global longitudinal strain (GLS) in breast cancer patients with low baseline risk for cardiotoxicity during cancer therapy. We also examined the relationship between echocardiographic strain, structural myocardial changes, and microRNA (miRNA) dysregulation associated with cancer treatment using an animal model. Methods: Echocardiography and blood tests were examined in 33 breast cancer patients with low baseline risk for cardiotoxicity during anthracycline treatment, with a follow-up at 12 months. Additionally, 16 Wistar rats received epirubicin (20 mg/kg over 4 weeks) to examine cardiac strain and structural changes. Moreover, circulating miRNA levels were assessed in patients’ serum using microarray at the end of the treatment and further analyzed in peripheral blood from the animal model. Results: Pathological GLS values were observed in 27.27% of patients after four cycles, with 15.15% showing reduced left ventricular ejection fraction (LVEF) after 12 months. In the animal model, epirubicin-induced circumferential strain (CS) decrease correlates with myocardial fibrosis assessed histologically and by a significant increase in COL1 and TGFB2 expression. Furthermore, we found a significant decrease in aquaporin1 expression associated with the presence of vacuoles in treated rats. Furthermore, dysregulation in the expression of miRNAs was observed in patients with cardiotoxicity. Among them, hsa-miR-122-5p is increased in both patient and rat serum post-treatment. Conclusions: A notable percentage of low-risk patients exhibited cardiac strain reduction due to cardiotoxicity. Epirubicin treatment caused structural heart changes in rats, highlighting miR-122-5p as a potential fibrosis marker that correlated with echocardiographic parameters. Full article
(This article belongs to the Special Issue Advances in Biomarker Discovery for Cardiovascular Disease)
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15 pages, 767 KiB  
Article
Prediction of Major Adverse Cardiovascular Events in Patients with Peripheral Artery Disease Using Circulating Immunomodulatory Proteins
by Ben Li, Farah Shaikh, Houssam Younes, Batool Abuhalimeh, Jason Chin, Khurram Rasheed, Abdelrahman Zamzam, Rawand Abdin and Mohammad Qadura
Biomedicines 2024, 12(12), 2842; https://doi.org/10.3390/biomedicines12122842 - 13 Dec 2024
Viewed by 1228
Abstract
Background/Objectives: The leading cause of death for people with peripheral artery disease (PAD) is major adverse cardiovascular events (MACE), including heart attacks and strokes. However, research into biomarkers that could help predict MACE in patients with PAD has been limited. Immunomodulatory proteins are [...] Read more.
Background/Objectives: The leading cause of death for people with peripheral artery disease (PAD) is major adverse cardiovascular events (MACE), including heart attacks and strokes. However, research into biomarkers that could help predict MACE in patients with PAD has been limited. Immunomodulatory proteins are known to significantly influence systemic atherosclerosis, suggesting they could be useful prognostic indicators for MACE in patients with PAD. In this study, we evaluated a broad panel of immunomodulatory proteins to identify those linked to MACE in individuals with PAD. Methods: We conducted a prognostic study involving a prospectively recruited cohort of 406 patients consisting of 254 with PAD and 152 without PAD. At the baseline, we measured the plasma concentrations of 17 circulating immunomodulatory proteins and followed the cohort for two years. The primary outcome was 2-year MACE, a composite of myocardial infarction, stroke, or death. Plasma protein concentrations were compared between patients with PAD with and without 2-year MACE using Mann–Whitney U tests. We further examined the prognostic potential of differentially expressed proteins through a Cox proportional hazards analysis, determining their independent associations with 2-year MACE while controlling for all the baseline demographic and clinical characteristics, including the existing coronary artery and cerebrovascular diseases. Additionally, A Kaplan–Meier analysis was performed to evaluate the 2-year freedom from MACE in patients with low versus high levels of the differentially expressed proteins based on the median plasma concentrations. Results: The mean age of the cohort was 68.8 years (SD 11.1), with 134 patients (33%) being female. During the two-year follow-up, 63 individuals (16%) developed MACE. The following proteins were significantly elevated in patients with PAD who experienced 2-year MACE compared to those who did not: galectin-1 (0.17 [SD 0.06] vs. 0.10 [SD 0.07] pg/mL, p = 0.012), alpha-1-microglobulin (16.68 [SD 7.48] vs. 14.74 [SD 6.71] pg/mL, p = 0.019), and galectin-9 (0.14 [SD 0.09] vs. 0.09 [SD 0.05] pg/mL, p = 0.033). The Cox proportional hazards analysis indicated that these three proteins were independently associated with 2-year MACE after adjusting for all the baseline demographic and clinical factors: galectin-1 (HR 1.45 [95% CI 1.09–1.92], p = 0.019), alpha-1-microglobulin (HR 1.31 [95% CI 1.06–1.63], p = 0.013), and galectin-9 (HR 1.35 [95% CI 1.02–1.78], p = 0.028). Over the two-year follow-up, patients with higher levels of galectin-1, galectin-9, and alpha-1-microglobulin had a lower freedom from MACE. Additional analysis showed that these three proteins were not significantly associated with 2-year MACE in patients without PAD. Conclusions: Among the 17 immunomodulatory proteins evaluated, galectin-1, galectin-9, and alpha-1-microglobulin were found to be independently and specifically associated with 2-year MACE in patients with PAD. Assessing the plasma concentrations of these proteins can aid in risk stratification for MACE in patients with PAD, helping to inform clinical decisions regarding multidisciplinary referrals to cardiologists, neurologists, and vascular medicine specialists. This information can also guide the aggressiveness of medical management, ultimately improving cardiovascular outcomes for patients with PAD. Full article
(This article belongs to the Special Issue Advances in Biomarker Discovery for Cardiovascular Disease)
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