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Identification of Novel Biomarkers Towards Improved Diagnosis and Management of Peripheral Vascular Diseases

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 September 2026 | Viewed by 10887

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Dr. Daniel P. Zalewski

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Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland
Interests: peripheral artery disease; chronic venous disease; aortic aneurysm; biomarker discovery; microRNA; gene expression profiling; visualisation and analysis of biological data in R

Special Issue Information

Dear Colleagues,

Diseases affecting peripheral vasculature (outside the coronary and cerebral circulation) encompass a variety of disorders, including atherosclerotic diseases (e.g., peripheral artery disease), venous disorders (e.g., chronic venous disease), aneurysmal diseases (e.g., abdominal aortic aneurysm), and congenital vascular malformations (e.g., Klippel-Trénaunay-Weber syndrome). Most of these diseases significantly impairs quality of life and are associated with severe morbidity and mortality. Despite advances in medical science, they continue to represent a substantial public health challenge. Current diagnostic modalities are often insufficiently sensitive or specific, missing many at-risk individuals during the early stages and leading to delayed or suboptimal interventions.

The identification of new molecular biomarkers for peripheral vascular diseases is critical for improving early detection, risk stratification, and personalised treatment strategies, addressing limitations of traditional diagnostic tools. Novel biomarkers can provide insights into underlying pathophysiological mechanisms, enabling more accurate prognostic assessments and facilitating the development of targeted therapies to reduce disease burden and improve patient outcomes.

This special issue invites articles from molecular research focused on the identification of novel biomarkers (at the levels of genome, epigenome, transcriptome, and proteome) with potential usefulness as diagnostic and therapeutic targets for peripheral vascular diseases.

Dr. Daniel P. Zalewski
Guest Editor

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Keywords

vascular pathophysiology
peripheral atherosclerosis
aneurysm
venous disorders
congenital vascular malformations
molecular biomarkers
diagnostic biomarkers
therapeutic targets

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Published Papers (6 papers)

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Research

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10 pages, 837 KB

Open AccessArticle

Influence of Hemostatic Disorder on Type II Endoleak Development After Endovascular Abdominal Aortic Aneurysm Repair

by Paweł Rynio, Magdalena Kłysz, Rabih Samad, Marta Bieniek, Dagmara Lisman, Anita Rybicka, Patryk Skórka, Paulina Lempek, Miłosław Cnotliwy, Arkadiusz Kazimierczak, Piotr Gutowski, Maria Jastrzębska and Aldona Siennicka

Int. J. Mol. Sci. 2026, 27(7), 3288; https://doi.org/10.3390/ijms27073288 - 4 Apr 2026

Viewed by 637

Abstract

Endovascular aneurysm repair (EVAR) is a widely used minimally invasive treatment for abdominal aortic aneurysms. However, postoperative type II endoleak (T2EL) remains a relevant complication associated with a risk of aneurysm rupture and the need for repeated imaging follow-up, resulting in exposure to ionizing radiation. Identification of biological factors predisposing to T2EL may improve risk stratification. This pilot study aimed to investigate whether disturbances in hemostasis are associated with early T2EL development after EVAR. A total of 103 patients treated with EVAR for symptomatic or asymptomatic abdominal aortic aneurysms in a tertiary vascular center were prospectively enrolled. Blood samples were collected preoperatively and one month postoperatively to assess fibrinogen, prothrombin fragment F1+2 (F1+2), thrombin–antithrombin complex (TAT), tissue plasminogen activator antigen (tPA), plasminogen activator inhibitor-1 (PAI-1) activity, and platelet activity. Computed tomography angiography (CTA) during follow-up was used to detect endoleaks and calculate their volume. Patients with T2EL had significantly lower levels of prothrombin fragment F1+2 and higher PAI-1 activity compared with patients without endoleak. No significant association was observed between the analyzed biomarkers and endoleak volume. These findings suggest that reduced thrombin generation and impaired fibrinolysis may contribute to endoleak formation after EVAR and warrant further investigation in larger, confirmatory studies. Full article

(This article belongs to the Special Issue Identification of Novel Biomarkers Towards Improved Diagnosis and Management of Peripheral Vascular Diseases)

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18 pages, 1513 KB

Open AccessArticle

Role of Lipoprotein(a) and Blood Cells Ratios in Peripheral Artery Disease

by Alexandra V. Tyurina, Olga I. Afanasieva, Marat V. Ezhov, Narek A. Tmoyan, Tatiana V. Balakhonova and Sergei N. Pokrovsky

Int. J. Mol. Sci. 2025, 26(20), 9918; https://doi.org/10.3390/ijms26209918 - 12 Oct 2025

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Abstract

Peripheral artery disease (PAD) is a major global health issue. This study investigated the relationship between lipoprotein(a) [Lp(a)], high-density lipoprotein cholesterol (HDL-C) to blood cells ratios, and PAD development. The study included 361 patients categorized into groups based on the presence of stenotic atherosclerosis in lower limb arteries (LLAs) diagnosed via duplex ultrasound. Group 1 (n = 238) had atherosclerosis at the first visit. A second visit involved 281 patients: 158 from Group 1, 32 new diagnoses (Group 2), and 91 with no atherosclerosis at either visit (Group 3). Laboratory analysis included lipid profiles, Lp(a), and complete blood counts, calculating ratios like Lp(a)/HDL-C and monocyte-to-HDL-C ratio (MHR). Showed patients with stenotic atherosclerosis had significantly higher Lp(a) (20.2 vs. 12.1 mg/dL, p < 0.01), MHR (0.54 vs. 0.39, p = 0.002), and Lp(a)/HDL-C ratios (20.9 vs. 8.8, p = 0.003). The combination of monocytes ≥ 0.55 × 10⁹/L and Lp(a) ≥ 30 mg/dL was present in 27% of PAD patients vs. 10% without (p < 0.01). Kaplan–Meier analysis indicated that high Lp(a) levels led to chronic limb ischemia 9.5 years earlier. Combined assessment of Lp(a) and monocyte-related ratios provides superior predictive value for PAD, suggesting clinical utility for risk stratification and early intervention. Full article

(This article belongs to the Special Issue Identification of Novel Biomarkers Towards Improved Diagnosis and Management of Peripheral Vascular Diseases)

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16 pages, 1095 KB

Open AccessArticle

Inflammation-Based Cell Ratios Beyond White Blood Cell Count for Predicting Postimplantation Syndrome After EVAR and TEVAR

by Ebubekir Sönmez, İzatullah Jalalzai and Ümit Arslan

Int. J. Mol. Sci. 2025, 26(19), 9753; https://doi.org/10.3390/ijms26199753 - 7 Oct 2025

Cited by 2 | Viewed by 1714

Abstract

Postimplantation syndrome (PIS) is an early inflammatory response following endovascular stent-graft implantation (EVAR and TEVAR), defined by culture-negative fever and leukocytosis. The patient’s preoperative inflammatory status is thought to play a central role in its development. This study aimed to evaluate whether the systemic inflammatory response index (SIRI) and the eosinophil-to-lymphocyte ratio (ELR) can serve as preoperative predictors of PIS. Clinical data from 300 patients who underwent aortic endograft implantation and laboratory results obtained 24 h before the procedure, and at 24 h, 72 h, and 1 week postoperatively, were prospectively recorded. PIS was defined as culture-negative fever ≥ 37.8 °C accompanied by leukocytosis ≥ 12,000/µL. Inflammation-based indices derived from complete blood count (SIRI and ELR), along with serum C-reactive protein (CRP) and albumin levels, were compared between patients with and without PIS. Logistic regression and receiver operating characteristic (ROC) analyses were performed to identify independent predictors. PIS developed in 55 patients (18.3%). Patients with PIS were younger (70.1 ± 8.6 vs. 72.7 ± 7.3 years; p = 0.042) and had larger aneurysm diameters and greater mural thrombus thickness. Preoperatively, leukocyte count, SIRI, and CRP levels were significantly higher in patients who developed PIS, whereas ELR and albumin levels were lower. Multivariable analysis showed that a larger aneurysm diameter (OR: 1.2; 95% CI: 1.0–1.3; p = 0.003), greater mural thrombus thickness (OR: 1.3; 95% CI: 1.0–1.6; p = 0.012), EVAR procedure (OR: 3.7; 95% CI: 1.2–6.3; p = 0.033), elevated SIRI (OR: 1.9; 95% CI: 1.2–3.1; p = 0.005), and higher CRP (OR: 1.4; 95% CI: 1.1–3.2; p = 0.003) were significantly associated with PIS. In contrast, increasing age, higher ELR, and higher albumin levels were associated with a reduced risk of PIS. Simple biomarkers routinely obtained from standard laboratory tests can contribute meaningfully to the preoperative prediction and postoperative identification of PIS. Their integration into risk stratification models and confirmation against definitive diagnostic criteria will require validation in larger, multicenter studies. Full article

(This article belongs to the Special Issue Identification of Novel Biomarkers Towards Improved Diagnosis and Management of Peripheral Vascular Diseases)

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27 pages, 2263 KB

Open AccessArticle

Molecular Signatures Related to Inflammation and Angiogenesis in Patients with Lower Extremity Artery Disease, Abdominal Aortic Aneurysm, and Varicose Veins: Shared and Distinct Pathways

by Daniel Zalewski, Paulina Chmiel, Przemysław Kołodziej, Marcin Feldo, Andrzej Stępniewski, Marta Ziaja-Sołtys, Joanna Łuszczak, Agata Stanek, Janusz Kocki and Anna Bogucka-Kocka

Int. J. Mol. Sci. 2025, 26(18), 8786; https://doi.org/10.3390/ijms26188786 - 9 Sep 2025

Cited by 1 | Viewed by 1512

Abstract

Lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA), and varicose veins (VV) are frequently underdiagnosed and undertreated peripheral vascular diseases that pose considerable public health challenges. More research is required to elucidate the pathophysiological mechanisms underlying these conditions and to identify novel diagnostic and therapeutic biomarkers. Therefore, in our study, we aimed to identify shared and distinct pathways associated with angiogenesis and inflammation in LEAD, AAA, and VV. The expression of 18 genes in peripheral blood mononuclear cells and the plasma levels of six proteins were compared between groups of 40 patients with LEAD, 40 patients with AAA, and 40 patients with VV. Independent RNA-seq and microRNA-seq data were integrated to predict differentially expressed transcription factors and microRNAs associated with the most significant genes. Gene Ontology functional analysis was performed to determine the potential biological effects of the observed dysregulations. The elevated expression of VEGFB and TGFB1, along with increased plasma levels of VEGF-C and reduced plasma levels of VEGF-A, were distinguishing features of patients with LEAD compared to those with AAA and VV. Decreased plasma levels of TGF-alpha and TGF-beta 1 were found to be indicative of varicose veins compared to individuals with arterial diseases (LEAD and AAA). Transcription factors and microRNAs potentially regulating the obtained signatures were identified and integrated into a hypothetical regulatory network. The observed dysregulations were found to be functionally associated with the response to hypoxia, the positive regulation of angiogenesis, chemotaxis, vascular permeability, and cell adhesion. The presented study identified dysregulations of key angiogenesis- and inflammation-related factors in peripheral blood mononuclear cells and plasma between LEAD, AAA, and VV patients, providing new insights into the shared and distinct molecular mechanisms underlying these diseases. Full article

(This article belongs to the Special Issue Identification of Novel Biomarkers Towards Improved Diagnosis and Management of Peripheral Vascular Diseases)

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14 pages, 273 KB

Open AccessArticle

Plasma Diacylglycerols Are Associated with Carotid Intima-Media Thickness Among Patients with Type 2 Diabetes: Findings from a Supercritical Fluid Chromatography/Mass Spectrometry-Based Semi-Targeted Lipidomic Analysis

by Naohiro Taya, Naoto Katakami, Kazuo Omori, Shigero Hosoe, Hirotaka Watanabe, Mitsuyoshi Takahara, Kazuyuki Miyashita, Yutaka Konya, Sachiko Obara, Ayako Hidaka, Motonao Nakao, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba and Iichiro Shimomura

Int. J. Mol. Sci. 2025, 26(14), 6977; https://doi.org/10.3390/ijms26146977 - 20 Jul 2025

Viewed by 1325

Abstract

Abnormalities in plasma lipoproteins observed in patients with diabetes promote atherosclerosis. However, the association between various lipid species and classes and atherosclerosis remains unclear. Here, we aimed to identify the plasma lipid characteristics associated with atherosclerosis progression in patients with diabetes. We performed semi-targeted lipidomic analysis of fasting plasma samples using supercritical fluid chromatography coupled with mass spectrometry in two independent patient groups with type 2 diabetes (n = 223 and 31) and evaluated cross-sectional associations between plasma lipids and carotid intima-media thickness (CIMT). Ten plasma lipid species, including eight diacylglycerols (DGs), and total DG levels were significantly associated with CIMT in both groups. Patients of the former group were partly observed for 5 years, and we investigated associations between DGs and CIMT progression in these patients (n = 101). As a result, 22 DGs among the 26 identified DGs and total DG (β = 0.398, p < 0.001) were significantly associated with the annual change in CIMT. Furthermore, plasma DG levels improved the predictive ability for CIMT progression, with an adjusted R-squared increase of 0.105 [95% confidence interval: 0.010, 0.232] in the models. Plasma DGs are associated with CIMT progression in patients with type 2 diabetes. Measurement of total plasma DG levels may be beneficial in assessing the risk of atherosclerosis progression. Full article

(This article belongs to the Special Issue Identification of Novel Biomarkers Towards Improved Diagnosis and Management of Peripheral Vascular Diseases)

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13 pages, 651 KB

Open AccessReview

The Role of High-Sensitivity Cardiac Troponin and Ischemia-Modified Albumin in Patients with Lower Extremity Peripheral Arterial Disease

by Vinko Boc, Aleš Blinc and Anja Boc

Int. J. Mol. Sci. 2025, 26(22), 11214; https://doi.org/10.3390/ijms262211214 - 20 Nov 2025

Viewed by 1056

Abstract

Peripheral arterial disease (PAD) is a growing global health concern associated with substantial morbidity, mortality, and healthcare costs. Prognostic stratification is currently based largely on clinical presentation, but patients with similar symptoms can have heterogeneous outcomes. Reliable biomarkers could improve the risk assessment of PAD patients and enable individualized patient management. High-sensitivity cardiac troponins (hs-cTn) and ischemia-modified albumin (IMA) have emerged as promising candidates. Hs-cTn appears to correlate with PAD severity and predict major adverse limb and cardiovascular events, likely reflecting subclinical myocardial injury in this patient population. Less extensively studied, IMA reflects oxidative stress, acidosis, and free radical activity. Its levels also seem to correlate with PAD severity, increasing with more advanced PAD. Notably, patients with advanced PAD but undetectable levels of biomarkers might have prognoses similar to those with milder disease, suggesting potential incremental prognostic value over clinical assessment. Despite these associations, the current applicability of hs-cTn and IMA remains limited by heterogeneous cut-off definitions and the absence of randomized controlled trials in the PAD population. Standardizing biomarker thresholds and prospective validation are crucial before integrating them into clinical practice. Both hs-cTn and IMA hold promise as tools for refined risk stratification in PAD, warranting further research. Full article

(This article belongs to the Special Issue Identification of Novel Biomarkers Towards Improved Diagnosis and Management of Peripheral Vascular Diseases)

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