Search Results (132)

Restenosis is the main cause of failure after stent implantation during angioplasty. The localized, sustained delivery of an antirestenotic drug may reduce smooth muscle cell (SMCs) proliferation and thereby limit neointimal hyperplasia. The aim of this study was to develop degradable sirolimus-eluting polymer coatings that can be applied on bioresorbable polymer-based scaffolds via an ultrasonic coating system. This is a novel approach because the detailed analysis of the coating procedure on bioresorbable polymeric scaffolds with the use of an ultrasonic system has not been reported thus far. It has been observed that the ultrasonic technique facilitates formation of a smooth coating, well-integrated with the scaffold. However, the drug dose is affected by the concentration of the coating solution and the number of layers. Therefore, these parameters can be used for tailoring the drug dose and release process. Although all types of the developed coatings provided sirolimus elution for at least 3 months, a more uniform, diffusion-controlled release profile was observed from coatings obtained from the 1.0% polymeric solution. The released drug showed antiproliferative activity against vascular SMCs, without any hemolytic or thrombogenic effects. The results of the study may be advantageous for further progress in the development and medical translation of polymeric vascular scaffolds with antirestenotic activity. Full article

Vascular smooth muscle cells (VSMCs) are central to the maintenance of vascular homeostasis and the progression of cardiovascular diseases (CVDs), owing to their remarkable phenotypic plasticity. This editorial introduces a Special Issue of Cells that compiles recent advances in our understanding of the molecular, epigenetic, metabolic, and mechanical mechanisms that govern VSMC behavior. Highlighted contributions explore the roles of RNA modifications, chromatin remodeling, lipid metabolism, and mechanotransduction in VSMC phenotypic switching, revealing new therapeutic targets and diagnostic opportunities. Together, these studies emphasize the multifactorial regulation of VSMC plasticity and its dual role in vascular repair and disease pathogenesis. Full article

Vein graft restenosis remains a major complication following coronary artery bypass grafting (CABG), mainly due to the abnormal proliferation of vascular smooth muscle cells (VSMCs) and impaired endothelial repair. While external stents (eStents) can provide mechanical support and limit adverse remodeling, traditional metallic stents are non-degradable and may induce chronic inflammation and fibrosis. In contrast, many bioresorbable materials degrade too quickly or lack mechanical strength. These challenges highlight the need for external stents that combine sufficient mechanical strength with biodegradability to support long-term graft patency. This is the first study that develops a chlorogenic acid–strontium (SrCA)-loaded polycaprolactone bioresorbable eStent that inhibits VSMC proliferation and enhances endothelial repair via Hippo–Yes-associated protein (YAP) signaling, addressing vein graft restenosis post-CABG. Combining mechanical support and biodegradability, it overcomes the limitations of non-degradable stents and rapidly degrading biomaterials, elucidates the potential of natural polyphenol–metal ion complexes in vascular remodeling, and offers an innovative strategy for the prevention of vein graft restenosis. Full article

The evolution of percutaneous coronary intervention (PCI) has led to significant advances in drug-coated balloon (DCB) technology, offering a stent-free alternative for treating coronary artery disease. While paclitaxel-coated balloons (PCBs) have been the standard, sirolimus-coated balloons (SCBs) are emerging as a viable alternative with distinct pharmacokinetic and clinical benefits. This review explores the mechanisms of action of paclitaxel and sirolimus, their impact on different plaque morphologies, and the clinical implications of DCB selection. Paclitaxel facilitates positive vascular remodeling and is particularly effective in fibrotic and lipid-rich plaques, but its poor penetration in calcified lesions remains a limitation. Sirolimus, with its homogeneous tissue distribution and anti-inflammatory properties, is better suited for unstable, lipid-rich, and inflammatory plaques, where it promotes plaque stabilization. Recent randomized trials and meta-analyses have compared SCBs vs. PCBs in both de novo lesions and in-stent restenosis, showing non-inferior outcomes. Additionally, DCBs demonstrate comparable efficacy to DES in small vessel disease, reducing the need for permanent metallic scaffolds. This review summarizes the current evidence on DCB selection based on plaque characteristics and highlights areas for further investigation in personalized PCI strategies. Given the narrative review design, the authors conducted a comprehensive literature search using databases such as PubMed and MEDLINE. Keywords included “drug-coated balloon”, “paclitaxel-coated balloon”, “sirolimus-coated balloon”, “in-stent restenosis”, and “plaque morphology”. Studies were selected based on relevance, including randomized controlled trials, registries, and meta-analyses. No formal inclusion/exclusion criteria or systematic screening were applied due to the nature of narrative synthesis. Full article

Introduction: Among aortic diseases in children, congenital defects such as coarctation of the aorta (CoA), interrupted aortic arch (IAA), hypoplastic aortic arch (HAA), and hypoplastic left heart syndrome (HLHS) predominate. Tissue patches are applied in pediatric cardiovascular surgery for the repair of congenital aortic defects as a filling material to replenish missing tissue or as a substitute material for the complete reconstruction of the vascular wall along the course of the vessel. This retrospective single-center study aimed to present the safety and feasibility of extracellular matrix (ECM) biological scaffolds in pediatric aortic surgery. Patients and methods: There were 26 patients (17 newborns and nine children), who underwent surgical procedures in the Department of Pediatric Cardiac Surgery (Poznań, Poland) between 2023 and 2024. The patients’ population was divided into two subgroups according to the hemodynamic nature of the primary diagnosis of the congenital heart defect and the performed pediatric cardiovascular surgery. The first group included 18 (72%) patients after aortic arch repair for interrupted aortic arch and/or hypoplastic aortic arch, while the second group included seven (28%) patients after aortopulmonary anastomosis. In the first group, patches were used to reconstruct the aortic arch by forming an artificial arch with three separate patches sewn together, primarily addressing the hypoplastic or interrupted segments. In the second group, patches were applied to augment the anastomosis site between the pulmonary trunk and the aortic arch, specifically at the connection points in procedures, such as the Damus–Kaye–Stansel or Norwood procedures. The analysis was based on data acquired from the national cardiac surgery registry. Results: The overall mortality in the presented group was 15%. All procedures were performed using median sternotomy with a cardiopulmonary bypass. The cardiopulmonary bypass (CPB) and aortic cross-clamp (AoX) median times were 144 (107–176) and 53 (33–79) min, respectively. There were two (8%) cases performed in deep hypothermic circulatory arrest (DHCA). The median postoperative stay in the intensive care unit (ICU) was 284 (208–542) h. The median mechanical ventilation time was 226 (103–344) h, including 31% requiring prolonged mechanical ventilation support. Postoperative acute kidney failure requiring hemodiafiltration (HDF) was noticed in 12% of cases. Follow-up data, collected via routine transthoracic echocardiography (TTE) and clinical assessments over a median of 418 (242.3–596.3) days, showed no evidence of patch-related complications such as restenosis, aneurysmal dilation, or calcification in surviving patients. One patient required reintervention on the same day due to a significantly narrow ascending aorta, unrelated to patch failure. No histological data from explanted patches were available, as no patches were removed during the study period. The median (Q1–Q3) hospitalization time was 21 (16–43) days. Conclusions: ProxiCor^® biological patches derived from the extracellular matrix can be safely used in pediatric patients with congenital aortic arch disease. Long-term follow-up is necessary to confirm the durability and growth potential of these patches, particularly regarding their resistance to calcification and dilation. Full article

Drug-coated balloons (DCBs) have emerged as a compelling alternative to drug-eluting stents in the treatment of coronary artery disease (CAD), offering the advantage of local drug delivery without permanent vascular scaffold implantation. Initially developed for managing in-stent restenosis, DCBs seem appealing for broader indications, particularly in small vessel disease and bifurcation lesions. While paclitaxel-based DCBs remain the most investigated, newer limus formulations are showing promise and appear to be a valid alternative in early trials. Evidence from recent randomized clinical trials (RCTs) and meta-analyses highlights DCBs as a safe and effective option in selected patients, with potential benefits including lower restenosis rates, reduced need for dual antiplatelet therapy, and avoidance of late stent-related complications. As new large-scale trials near completion, DCBs are poised to take on a broader role in the treatment of CAD, particularly in patients where “leaving nothing behind” offers a clinical advantage. This review offers an overview of the DCB platforms commercially available, showing pharmacological differences, providing current indications in practical guidelines, and analyzing the most recent and impactful RCTs and meta-analyses in the field. Full article

(1) Background: Peripheral arterial CT angiography (CTA) is an alternative to conventional angiography for diagnosing lower extremity artery disease (LEAD). However, severe arterial calcifications often hinder accurate assessment of arterial stenosis. This study evaluated the diagnostic performance of subtraction CTA with volume position matching compared to conventional CTA, using invasive digital subtraction angiography (DSA) as the gold standard. (2) Methods: Thirty-two patients with LEAD (mean age: 69.6 ± 10.8 years; M/F = 28:4) underwent subtraction CTA and DSA. The arterial tree was divided into 20 segments per patient, excluding segments with a history of bypass surgery. Subtraction was performed separately for each limb using volume position matching. Maximum intensity projections were reconstructed from both conventional and subtraction CTA data. Percent stenosis per arterial segment was measured using calipers and compared with DSA. Segments were classified as stenotic (>50% luminal narrowing) or not, with heavily calcified or stented segments assigned as incorrect. (3) Results: Of 640 segments, 636 were analyzed. Subtraction CTA and conventional CTA left 13 (2.0%) and 160 (25.2%) segments uninterpretable, respectively. Diagnostic accuracies (accuracy, precision, recall, macro F1 score) for subtraction CTA were 0.885, 0.884, 0.936, and 0.909, compared to 0.657, 0.744, 0.675, and 0.708 for conventional CTA. (4) Conclusions: Subtraction CTA with volume position matching is feasible and achieves high diagnostic accuracy in patients with severe calcific sclerosis. Full article

More than 400 different types of post-translational modifications (PTMs), including O-GlcNAcylation and phosphorylation, combine to co-ordinate almost all aspects of protein function. Often, these PTMs overlap and the specific relationship between O-GlcNAcylation and phosphorylation has drawn much attention. In the last decade, the significance of this dynamic crosstalk has been linked to several chronic pathologies of cardiovascular origin. However, very little is known about the pathophysiological significance of this crosstalk for vascular smooth muscle cell dysfunction in cardiovascular disease. O-GlcNAcylation occurs on serine and threonine residues which are also targets for phosphorylation. A growing body of research has now emerged linking altered vascular integrity and homeostasis with highly regulated crosstalk between these PTMs. Additionally, a significant body of evidence indicates that O-GlcNAcylation is an important contributor to the pathogenesis of neointimal hyperplasia and vascular restenosis responsible for long-term vein graft failure. In this review, we evaluate the significance of this dynamic crosstalk and its role in cardiovascular pathologies, and the prospects of identifying possible targets for more effective therapeutic interventions. Full article

Drug-eluting stents, which release antiproliferative agents such as sirolimus and everolimus, were developed to reduce the risk of restenosis associated with bare-metal stents. However, despite their proven clinical efficacy, concerns remain regarding in-stent restenosis due to delayed endothelial healing and the risk of late thrombotic events. In this study, we aimed to determine the vascular effects of sirolimus and everolimus on isolated human saphenous vein (SV) samples obtained from patients undergoing coronary artery bypass surgery. SV rings were subjected to sirolimus and everolimus in acute and pretreatment conditions in vitro. Increasing concentrations of sirolimus (10⁻⁸–10⁻⁵ M), everolimus (10⁻⁸–10⁻⁵ M), and their vehicle were administered to SV rings precontracted with phenylephrine (Phe,10⁻⁶–5 × 10⁻⁶ M) to evaluate their direct vascular effects. Additionally, SV rings were incubated (16 h) either with sirolimus (10⁻⁵ M), everolimus (10⁻⁶ M), or the vehicle. Thereafter, the contractile responses to Phe (10⁻⁸–10⁻⁴ M), and the endothelium-dependent and endothelium-independent relaxant responses to acetylcholine (ACh, 10⁻⁸–10⁻⁴ M) and sodium nitroprusside (SNP,10⁻⁸–10⁻⁴ M) were determined, respectively. Our findings demonstrated that sirolimus and everolimus did not exert direct relaxant and modulatory effects on vascular function in isolated human SVs. Hence, the preservation of contractile and relaxant responses with sirolimus and everolimus may have clinical implications in the context of DES implantation. Full article

Cardiovascular disease remains the leading cause of morbidity and mortality worldwide. Key challenges such as atherosclerosis, in-stent restenosis, and maintaining arteriovenous access, pose urgent problems for effective treatments for both coronary artery disease and chronic kidney disease. The next generation of active implantables will offer innovative solutions and research opportunities to reduce the economic and human cost of disease. Current treatments rely on vascular stents or synthetic implantable grafts to treat vessels when they block such as through in-stent restenosis and haemodialysis graft failure. This is often driven by vascular cell overgrowth termed neointimal hyperplasia, often in response to inflammation and injury. The integration of biosensors into existing approved implants will bring a revolution in cardiovascular devices and into a promising new era. Biosensors that allow real-time vascular monitoring will provide early detection and warning of pathological cell growth. This will enable proactive wireless treatment outside of the traditional hospital settings. Ongoing research focuses on the development of self-reporting smart cardiovascular devices, which have shown promising results using a combination of virtual in silico modelling, bench testing, and preclinical in vivo testing. This innovative approach holds the key to a new generation of wireless data solutions and wireless powered implants to enhance patient outcomes and alleviate the burden on global healthcare budgets. Full article

Smooth muscle cell (SMC) phenotypic transition contributes to several major vascular diseases such as intimal hyperplasia and restenosis, atherosclerosis, and aneurysm. However, the molecular mechanisms underlying this process are not fully understood. The objectives of this study are to determine the role of mRNA N⁶-methyladenosine (m6A) modification in SMC phenotypic modulation and injury-induced neointima formation. By using an m6A quantification kit, we found that m6A levels are altered during the early stage of SMC phenotypic modulation. RNA sequencing revealed that m6A modifications in the mRNAs of 708 genes are elevated while modifications in the mRNAs of 300 genes are decreased. These modifications occur in genes widely distributed in most chromosomes and involved in many cellular processes and signaling/gene regulations. Meanwhile, the regulators for m6A modifications are altered by PDGF-BB, a known factor inducing SMC phenotypic modulation. Although m6A writers and erasers are not altered during SMC phenotypic modulation, m6A reader YTHDF1 is dramatically reduced as early as 12 h following PDGF-BB treatment, a time much earlier than the downregulation of SMC contractile proteins. Importantly, the overexpression of YTHDF1 reverses the expression of SMC contractile proteins, suggesting a restoration of contractile SMC phenotype. By using a rat carotid artery balloon-injury model, we found that injury significantly decreases YTHDF1 levels in the medial SMCs while inducing neointima formation. Of significance, restoring YTHDF1 expression through lentiviral transduction blocks injury-induced neointima formation. Moreover, YTHDF1 delivery restores the expression of SMC contractile proteins that is diminished in arterial media layers due to the injury. These data demonstrate that YTHDF1 plays a protective role in maintaining the contractile SMC phenotype and vascular homeostasis during injury-induced pathological vascular remodeling. Full article

Arterial diseases (ADs) are a significant health problem, with high mortality and morbidity rates. Endovascular interventions, such as balloon angioplasty (BA), bare-metal stents (BMSs), drug-eluting stents (DESs) and drug-coated balloons (DCBs), have made significant progress in their treatments. However, the issue has not been fully resolved, with restenosis remaining a major concern. In this context, bioresorbable vascular stents (BVSs) have emerged as a promising area of investigation. This manuscript includes articles that assess the use of BVSs. Studies have identified ongoing challenges, such as negative vascular remodeling and elastic recoil post-angioplasty, stent-related injury, and in-stent restenosis following BMS placement. While DESs have mitigated these issues to a considerable extent, their durable structures are unable to prevent late stent thrombosis and delay arterial recovery. BVSs, with their lower support strength and tendency towards thicker scaffolds, increase the risk of scaffold thrombosis. Despite inconsistent study results, the superiority of BVSs over DESs has not been demonstrated in randomized trials, and DES devices continue to be the preferred choice for most cases of arterial disease. Esprit BTK (Abbott Vascular) received approval from the US FDA for below-knee lesions in 2024, offering hope for the use of BVSs in other vascular conditions. Enhancing the design and thickness of BVS scaffolds may open up new possibilities. Large-scale and longer-term comparative studies are still required. This article aims to provide an overview of the use of biodegradable stents in the endovascular treatment of vascular stenosis. Full article

The PAK (p21-activated kinases) family is a class of intracellular signal transduction protein kinases that regulate various cellular functions, mainly through their interactions with small GTP enzymes. PAK1 and PAK2 in the PAK kinase family are key signal transduction molecules that play important roles in various biological processes, including morphological changes, migration, proliferation, and apoptosis, and are involved in the progression of many diseases. Abnormal expression or dysregulation of PAK1 and PAK2 may be associated with several diseases, including cancer, neurological diseases, etc. The current research mainly focuses on studying the role of PAK and PAK inhibitors in the regulation of cancer progression, but relatively few reports are available that explore their potential role in cardiovascular diseases. Vascular injury and repair are complex processes involved in many cardiovascular conditions, including atherosclerosis, restenosis, and hypertension. Emerging research suggests that PAK1 and PAK2 have pivotal roles in vascular endothelial cell functions, including migration, proliferation, and angiogenesis. These kinases also modulate vascular smooth muscle relaxation, vascular permeability, and structural alterations, which are critical in the development of atherosclerosis and vascular inflammation. By targeting these activities, PAK proteins are essential for both normal vascular physiology and the pathogenesis of vascular diseases, highlighting their potential as therapeutic targets for vascular health. This review focuses on recent studies that offer experimental insights into the mechanisms by which PAK1 and PAK2 regulate the biological processes of vascular injury and repair and the therapeutic potential of the current existing PAK inhibitors in vascular-related diseases. The limitations of treatment with some PAK inhibitors and the ways that future development can overcome these challenges are also discussed. Full article

Chronic kidney disease (CKD) affects more than 10% of the world’s population. Hemodialysis, along with peritoneal dialysis and renal transplant, is one of the renal replacement therapies offered to patients with CKD/end-stage renal disease (ESRD). To proceed with hemodialysis, vascular access is required. The two means of long-term access are arteriovenous fistula (AVF) and arteriovenous graft (AVG). Multiple therapies have been created to help the long-term patency of AVFs. These therapies are needed as 40% of AVFs fail within the first year and additional intervention is required. Much of the existing research has focused on biomarkers, immune cells, hypoxia, and cell-based therapies. Regeneration therapy using mesenchymal stem cells seeks to investigate other ways that we can treat AVF failure. Mesenchymal stem cells are harvested as two main types, fetal and adult. Fetal cells are harvested at different times in fetal gestation and from multiple sources, placental blood, Whartons jelly, and amniotic stem cell fluid. Taken together, this review summarizes the different preclinical/clinical studies conducted using different types of MSCs towards vascular regenerative medicine and further highlights its potential to be a suitable alternative approach to enhance AVF patency. Full article

Background: Carotid artery stenting (CAS) could lead to a modification of the carotid bifurcation geometry with possible clinical implications. This study aimed to clarify the geometrical impact of three carotid stents with different designs on the carotid bifurcation and its clinical consequences. Methods: This was a retrospective single-center study. We included all patients who underwent CAS in a 3-year period. Anatomical changes of the carotid bifurcation were evaluated by reviewing angiographic images. The population was divided into three groups based on the stent implanted: Group 1 (Carotid Wallstent), Group 2 (Roadsaver), and Group 3 (C-Guard). Results: A total of 226 patients were included. The mean age was 77.0 ± 7.4 years and 72.5% (164/226) were male. Three different stents were implanted into three groups: Group 1 (n = 131/226, 58%), Group 2 (n = 57/226, 25.2%), and Group 3 (n = 38/226, 16.8%). The mean pre-stent implantation CCA-ICA angle of the entire population was 155 ± 14.9°, and the post-CAS angle was 167.7 ± 8.7° (p = 0.0001). In every subgroup, the difference was statistically different, with the biggest difference registered in Group 2 (−16.1 ± 13.2°). Regarding stent oversizing, there was a significant relationship between CCA oversizing and CCA-ICA angle modification (p = 0.006). During follow-up, a total of 14 (6.2%) restenoses were registered. The mean CCA-ICA angle modification in the restenosis group was −9.5 ± 14.4° vs. −12.8 ± 11.9° in the no-restenosis group with no significant statistical differences were outlined (p = 0.3). Conclusions: Compared to the Carotid Wallstent and C-Guard, the Roadsaver stent appears to have a lower adaptability to the carotid vascular territory, resulting in a higher CCA-ICA angle modification after implantation, with no impact on the stent restenosis rate. Full article