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Biomolecules
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Biomolecular Sciences and Precision Medicine in Vascular Disease
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Biomolecular Sciences and Precision Medicine in Vascular Disease

A Special Issue of Biomolecules (ISSN 2218-273X) belonging to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 3974

Editor

Prof. Dr. Raffaele Serra

E-Mail Website
Guest Editor
1. Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
2. Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
Interests: cardiovascular disease; vascular surgery; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Vascular disease (VD) is the leading cause of morbidity and mortality worldwide. VD includes atherosclerotic manifestations such as peripheral artery disease (PAD), acute limb ischemia (ALI), and carotid stenosis (CS); central and peripheral aneurysms; chronic venous disease (CVD) and venous thromboembolism (VTE); and vascular wounds such as diabetic foot ulcer (DFU), venous leg ulcer (VLU), and arterial leg ulcer (ALU).

Novel biomarkers related to molecular sciences research and application may be used as screening and risk-assessment tools to identify patients who are vulnerable to VD in the new context of Precision Medicine. In fact, the recent experimental technical progress related to biology, chemistry, and molecular medicine has allowed scientists to find effective biomarkers to assess and identify high-risk individuals, ensure prompt and accurate diagnosis, and follow up on patients who have undergone medical treatment and/or vascular and endovascular surgery procedures.

Currently, the complex approach to illness considers biology and medicine to be connected to social and molecular determinants of health that are strictly related to molecular sciences and biomarkers.

For this Special Issue, we invite investigators to contribute original research and review papers that provide new insights into the biomolecular mechanisms of VD, as well as work on new diagnostic and prognostic tools/biomarkers related to therapeutic strategies.

Prof. Dr. Raffaele Serra
Guest Editor

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 250 words) can be sent to the Editorial Office for assessment.

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-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules 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 2700 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

  • precision medicine
  • vascular disease
  • vascular surgery

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Published Papers (3 papers)

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Research

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14 pages, 1973 KB  
Article
Trefoil Factor 3 as a Biomarker for Peripheral Artery Disease
by Ben Li, Hamzah Khan, Farah Shaikh, Abdelrahman Zamzam, Ravel Raphael, Muzammil H. Syed, Rawand Abdin and Mohammad Qadura
Biomolecules 2026, 16(6), 892; https://doi.org/10.3390/biom16060892 - 17 Jun 2026
Viewed by 634
Abstract
Background: While trefoil factor 3 (TFF3) has been linked to cardiovascular disease, its role in peripheral artery disease (PAD) remains largely unexplored. In this prospective study, we assessed three pre-selected circulating biomarkers and found that TFF3 demonstrated the strongest association with the presence [...] Read more.
Background: While trefoil factor 3 (TFF3) has been linked to cardiovascular disease, its role in peripheral artery disease (PAD) remains largely unexplored. In this prospective study, we assessed three pre-selected circulating biomarkers and found that TFF3 demonstrated the strongest association with the presence of PAD. Building on this finding, we integrated plasma TFF3 concentrations with clinical characteristics to construct predictive models aimed at identifying individuals with PAD and estimating their risk of major adverse limb events (MALE) over a two-year follow-up period. Methods: A total of 476 individuals were prospectively recruited, including 312 patients with PAD and 164 controls without PAD. At study entry, circulating concentrations of TFF3, oncostatin M (OSM), and brain-derived neurotrophic factor (BDNF) were quantified, and all participants were subsequently monitored for a two-year period. The primary endpoint was the occurrence of MALE within two years, comprising acute limb ischemia, major amputation, or lower extremity revascularization by either open surgical or endovascular approaches. PAD diagnosis served as the secondary outcome and was established by an ankle–brachial index (ABI) ≤ 0.9 or toe–brachial index (TBI) ≤ 0.67 in the presence of reduced or absent pedal pulses. For predictive model development, the cohort was randomly divided into training (70%) and testing (30%) sets. A random forest algorithm incorporating clinical variables and plasma TFF3 levels was developed and optimized using 10-fold cross-validation. Model discrimination was quantified using the area under the receiver operating characteristic curve (AUROC). For prognostic evaluation, patients were classified into low- and high-risk groups based on the optimal ROC-derived probability threshold of 0.60, and MALE-free survival between groups was assessed using Cox proportional hazards regression. Results: Among the three candidate biomarkers evaluated, only TFF3 demonstrated a significant association with PAD. Patients with PAD exhibited higher circulating TFF3 concentrations than those without PAD (7.27 ± 3.36 vs. 5.89 ± 2.67 pg/mL; p < 0.001), whereas OSM and BDNF showed no significant differences between groups. Over the two-year follow-up period, MALE occurred in 28 patients (9%). Predictive models combining plasma TFF3 measurements with clinical variables achieved strong performance for both PAD detection and 2-year MALE risk estimation, yielding AUROCs of 0.79 and 0.85, respectively. Furthermore, patients classified as high risk by the model experienced a significantly increased hazard of MALE during follow-up (HR 1.12, 95% CI 1.10–1.19; p = 0.003). Variable importance analysis revealed that TFF3 was the most influential predictor of MALE, followed by age and smoking history. Conclusions: Combining plasma TFF3 levels with readily available clinical characteristics enabled the development of a predictive model with good discriminatory ability for both PAD diagnosis and estimation of 2-year MALE risk. Such an approach may enhance risk stratification by identifying patients at elevated risk earlier in their disease course, thereby informing decisions related to vascular testing, referral for specialist evaluation, and implementation of targeted treatment strategies. Full article
(This article belongs to the Special Issue Biomolecular Sciences and Precision Medicine in Vascular Disease)
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19 pages, 576 KB  
Article
Molecular Drivers of Vascular Adaptation in Young Athletes: An Integrative Analysis of Endothelial, Metabolic and Lipoprotein Biomarkers
by Jonas Haferanke, Lisa Baumgartner, Maximilian Dettenhofer, Stefanie Huber, Frauke Mühlbauer, Tobias Engl, Paulina Wasserfurth, Karsten Köhler, Renate Oberhoffer, Thorsten Schulz and Sebastian Freilinger
Biomolecules 2025, 15(12), 1726; https://doi.org/10.3390/biom15121726 - 11 Dec 2025
Cited by 3 | Viewed by 1169
Abstract
Adolescence is a critical window for cardiovascular (CV) development, yet the molecular drivers of vascular adaptation to regular exercise in youth remain poorly understood. This cross-sectional study assessed vascular structure and function alongside endothelial, metabolic, and lipoprotein biomarkers in 203 healthy young athletes [...] Read more.
Adolescence is a critical window for cardiovascular (CV) development, yet the molecular drivers of vascular adaptation to regular exercise in youth remain poorly understood. This cross-sectional study assessed vascular structure and function alongside endothelial, metabolic, and lipoprotein biomarkers in 203 healthy young athletes (aged 10–16). Vascular phenotyping included carotid intima-media thickness (IMT), pulse wave velocity, and carotid deformation indices (strain, strain rate). Circulating nitric oxide (NO), endothelin-1, free triiodothyronine (fT3), leptin, low-density lipoprotein, and high-density lipoprotein were analyzed. Associations were examined using hierarchically adjusted multivariable linear regression, mediation and moderation were tested and sex-stratified/matched analyses were conducted. While training volume was not associated with endothelial markers, leptin was correlated positively with NO and negatively with diastolic strain rate, suggesting dual vascular actions. fT3 was inversely associated with IMT, indicating a potential protective role in vascular remodeling. Lipoprotein profiles showed no independent associations with vascular parameters. Hemodynamic load, particularly systolic blood pressure, emerged as the dominant determinant of arterial stiffness. Sex-specific differences across biomarkers and vascular indices support a multifactorial model: in active youth, vascular phenotype reflects hemodynamics, body composition, and endocrine–metabolic signals more than training; longitudinal mechanistic studies should clarify causal pathways and guide individualized cardiovascular risk profiling. Full article
(This article belongs to the Special Issue Biomolecular Sciences and Precision Medicine in Vascular Disease)
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Review

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24 pages, 741 KB  
Review
Extracellular Vesicles as Biomarkers for Vascular Disease
by Davide Costa, Michele Andreucci, Nicola Ielapi, Teresa Faga, Antonio Mazza, Giulio Accarino, Umberto Marcello Bracale and Raffaele Serra
Biomolecules 2026, 16(4), 608; https://doi.org/10.3390/biom16040608 - 20 Apr 2026
Viewed by 1179
Abstract
Vascular diseases (VD) remain a leading global cause of morbidity and mortality, often developing silently before manifesting as severe complications like stroke or ischemia. Traditional diagnostic imaging provides essential anatomical data but frequently fails to capture the dynamic molecular processes underlying vascular pathology. [...] Read more.
Vascular diseases (VD) remain a leading global cause of morbidity and mortality, often developing silently before manifesting as severe complications like stroke or ischemia. Traditional diagnostic imaging provides essential anatomical data but frequently fails to capture the dynamic molecular processes underlying vascular pathology. This narrative review summarizes current evidence regarding Extracellular Vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, as emerging biomarkers and mediators in vascular conditions. The review evaluates the biological mechanisms of EVs across several disorders, including arterial aneurysms, peripheral artery disease, carotid stenosis, and venous thromboembolism. Findings indicate that EVs concentration and molecular cargo, particularly microRNAs and proteins, reflect the physiological state of parent cells, offering a “liquid biopsy” for vascular inflammation, endothelial dysfunction, and plaque vulnerability. Furthermore, the review explores the therapeutic potential of stem cell-derived EVs in promoting angiogenesis and tissue repair in chronic vascular ulcers. Despite these advances, the review concludes that the clinical implementation of EV-based diagnostics faces significant hurdles, primarily due to the lack of standardized isolation and characterization methods. Addressing these methodological challenges is crucial for translating EV research into routine clinical practice. Full article
(This article belongs to the Special Issue Biomolecular Sciences and Precision Medicine in Vascular Disease)
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