Recent studies of platelet endothelial cell adhesion molecule-1 (PECAM-1 [CD31])-deficient mice have revealed that this molecule plays an important role in controlling the activation and survival of cells on which it is expressed. In this review, we focus on the complex cytoplasmic domain of PECAM-1 and describe what is presently known about its structure, posttranslational modifications, and binding partners. In addition, we summarize findings that implicate PECAM-1 as an inhibitor of cellular activation via protein tyrosine kinase–dependent signaling pathways, an activator of integrins, and a suppressor of cell death via pathways that depend on damage to the mitochondria. The challenge of future research will be to bridge our understanding of the functional and biochemical properties of PECAM-1 by establishing mechanistic links between signals transduced by the PECAM-1 cytoplasmic domain and discrete cellular responses.

The role of platelets in hemostasis and thrombosis is dependent on a complex balance of activatory and inhibitory signaling pathways. Inhibitory signals released from the healthy vasculature suppress platelet activation in the absence of platelet receptor agonists. Activatory signals present at a site of injury initiate platelet activation and thrombus formation; subsequently, endogenous negative signaling regulators dampen activatory signals to control thrombus growth. Understanding the complex interplay between activatory and inhibitory signaling networks is an emerging challenge in the study of platelet biology, and necessitates a systematic approach to utilize experimental data effectively. In this review, we will explore the key points of platelet regulation and signaling that maintain platelets in a resting state, mediate activation to elicit thrombus formation, or provide negative feedback. Platelet signaling will be described in terms of key signaling molecules that are common to the pathways activated by platelet agonists and can be described as regulatory nodes for both positive and negative regulators.

While current oral antiplatelet therapies benefit many patients, they deregulate the hemostatic balance leaving patients at risk of systemic side-effects such as hemorrhage. Dual antiplatelet treatment is the standard approach, combining aspirin with P2Y12 blockers. These therapies mainly target autocrine activation mechanisms (TxA2, ADP) and, more recently, the use of thrombin or thrombin receptor antagonists have been added to the available approaches. Recent efforts to develop new classes of anti-platelet drugs have begun to focus on primary platelet activation pathways such as through the immunoreceptor tyrosine-based activation motif (ITAM)-containing collagen receptor GPVI/FcRγ-chain complex. There are already encouraging results from targeting GPVI, with reduced aggregation and smaller arterial thrombi, without major bleeding complications, likely due to overlapping activation signaling pathways with other receptors such as the GPIb–V–IX complex. An alternative approach to reduce platelet activation could be to inhibit this signaling pathway by targeting the inhibitory pathways intrinsic to platelets. Stimulation of endogenous negative modulators could provide more specific inhibition of platelet function, but is this feasible? In this review, we explore the potential of the two major platelet immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing inhibitory receptors, G6b-B and PECAM-1, as antithrombotic targets.

Platelets are not only crucial for hemostasis but also play a vital role in a wide range of physiological and pathological processes. The continuous expansion of knowledge in platelet biology holds significant therapeutic implications, offering new avenues for treating various diseases. Sustained research and innovation in platelet-targeted therapies, coupled with a deeper understanding of their molecular mechanisms, will pave the way for novel and more effective treatment approaches, ultimately improving patient outcomes and advancing medical science.

Von Willebrand factor (VWF) and VWF propeptide (VWFpp) are stored in eccentric nanodomains within platelet alpha-granules. VWF and VWFpp can undergo differential secretion following Weibel-Palade body exocytosis in endothelial cells; however, it is unclear if the same process occurs during platelet alpha-granule exocytosis. Using a high-throughput 3-dimensional super-resolution imaging workflow for quantification of individual platelet alpha-granule cargo, we studied alpha-granule cargo release in response to different physiological stimuli.

The ALL-RISE trial evaluated whether FFRangio, an angiography-derived fractional flow reserve technology from Medtronic, could safely replace traditional pressure wire-based physiological assessment for guiding percutaneous coronary intervention in patients with intermediate coronary stenoses. Enrolling 1,930 patients across 59 international sites, the study randomly assigned participants to either FFRangio or pressure wire assessment, which included either FFR or nonhyperemic pressure ratio measurement. The primary endpoint of death, myocardial infarction, or unplanned revascularization at one year occurred in 6.9% of the FFRangio group and 7.1% of the pressure wire group, demonstrating noninferiority. FFRangio significantly reduced procedural burden with shorter procedure duration (39 versus 42 minutes), less fluoroscopy time (9 versus 12 minutes), and lower contrast volume (100 versus 105 milliliters). However, FFRangio identified more physiologically significant lesions and led to higher intervention rates (44.3% versus 35.4%). These findings, published alongside the similar FAST III trial results, support FFRangio as a viable wire-free alternative for guiding revascularization decisions, though they contrast with mixed evidence from QFR studies, providing clinicians with an additional option for streamlined coronary assessment.

Electrospun aligned CS/SF scaffolds loading heparin are successfully fabricated. Scaffolds exhibit oriented fibers, good mechanical properties, hydrophilicity, and controllable degradation. The scaffolds synergistically improve anticoagulant, antibacterial and endothelialization effect. Scaffolds represents a promising candidate for next-generation vascular grafts and interventional devices. The study provides experimental and theoretical basis for artificial cardiovascular implants.

Stentless PCI with DCB was frequently used in patients undergoing PCI for bypass graft lesions in Japan and was not associated with a significant difference in 1-year clinical outcomes compared with contemporary DES-based PCI strategies.

Patients preparing for coronary angioplasty are rarely handed a choice between stent types in any meaningful sense today. Yet, many still arrive at consultation having read, somewhere online, that one kind of stent is inherently superior to another. The honest answer is more interesting than a simple hierarchy, and understanding it equips a patient to ask better questions and to understand, with genuine clarity, what is actually being placed inside their artery.

In-stent restenosis of coronary arteries is the major reason for the recurrence of occlusion after successful percutaneous coronary intervention (PCI) and occurs in 20–50% of patients.1 The development of in-stent restenosis depends on complex cellular interactions within the vessel wall involving endothelial cells (ECs), smooth muscle cells (SMCs), fibroblasts, lymphocytes, and macrophages.2 Vessel injury from balloon angioplasty and stenting cause the release of soluble mediators that initiate cellular activation, migration, proliferation, extracellular matrix production and secretion via autocrine or paracrine mechanisms.

Despite significant advances in stent technology, long-term complications—such as restenosis and stent thrombosis—remain relatively common and clinically impactful due to their association with recurrent myocardial infarction and adverse outcomes. Among the causes of stent failure, neoatherosclerosis has gained recognition as a key pathological mechanism, driven by impaired vascular healing, chronic inflammation, platelet activation, and immune responses following coronary stenting. Advances in diagnostic accuracy, particularly intracoronary imaging, have provided new insights into its development. In response, emerging strategies—including refined pharmacotherapy, targeted intraprocedural interventions, novel stent designs, and alternative drug-delivery systems—are being explored. This review presents recent preclinical, diagnostic, and clinical advances in understanding and addressing neoatherosclerosis and discusses current and emerging therapeutic approaches (Graphical Abstract).

Conventional cardiology has long treated coronary artery disease like a plumbing problem, using stents or bypass surgery to physically open blocked arteries. However, landmark research is fundamentally challenging this approach. The COURAGE trial, which followed over 2,000 patients with stable heart disease, and the ISCHEMIA trial, involving 5,179 patients with moderate-to-severe ischemia, revealed surprising findings: patients receiving immediate stent placement plus medical therapy showed no significant survival advantage over those treated with medication and lifestyle changes alone, with benefits sustained over up to 15 years of follow-up. These massive studies suggest the human body functions more like a self-healing biological system than mechanical plumbing. This paradigm shift has profound implications for cardiac care, suggesting that for many patients with stable coronary artery disease, aggressive pharmaceutical interventions and lifestyle modifications—potentially including dietary changes—may be as effective as invasive procedures, potentially sparing millions from unnecessary surgery while reducing healthcare costs and associated risks.

The LIBREXIA ACS trial evaluated milvexian, a selective factor XIa inhibitor, as a potential treatment to prevent harmful blood clots while preserving normal clotting in acute coronary syndrome patients. Researchers randomized 14,194 participants to receive oral milvexian 25 mg twice daily or placebo alongside standard antiplatelet therapy. Following a median of ten months, the trial was discontinued after a preplanned interim analysis indicated futility. The primary efficacy endpoint of cardiovascular death, myocardial infarction, or ischaemic stroke showed no difference between groups at 5.4% for milvexian versus 5.1% for placebo. Importantly, the safety profile was reassuring, with no increased intracranial or fatal bleeding observed in either group. These findings have implications for ongoing LIBREXIA trials in atrial fibrillation and stroke prevention, which involve different patient populations and disease contexts. While milvexian demonstrated no efficacy advantage in ACS, the favorable bleeding safety profile warrants continued investigation in other clinical settings.

This WikiDoc resource page provides a comprehensive medical information portal addressing percutaneous coronary intervention (PCI) management in patients experiencing in-stent restenosis, a condition where previously placed coronary stents become re-narrowed. The page aggregates medical literature, clinical evidence, and professional resources from major journals including the New England Journal of Medicine, Lancet, and BMJ, alongside multimedia educational content such as presentations, images, and videos. It directs users to evidence-based medicine resources via the Cochrane Collaboration and clinical trial registries at ClinicalTrials.gov, while incorporating regulatory guidance from the FDA and clinical recommendations from NICE and NHS PRODIGY. The platform offers multifaceted support for healthcare providers through diagnostic study information, treatment protocols, continuing medical education, and risk assessment tools. Additionally, it provides patient-centered resources including educational handouts and community discussion forums. This consolidated approach to in-stent restenosis management reflects the clinical significance of this common interventional cardiology challenge and supports informed decision-making across the medical community.

This ESC Congress 2026 presentation, delivered by Dr. Ryo Bando from Tokushima University Hospital, presents a propensity-matched three-year outcome analysis comparing drug-coated balloon (DCB)–only strategies with drug-eluting stents (DES) in large-vessel complex percutaneous coronary intervention (PCI). The study evaluates whether DCB-only approaches provide comparable efficacy and safety to traditional DES implantation in complex coronary lesions. This comparison is clinically significant as it addresses the potential benefits of DCB therapy in reducing stent-related complications while maintaining therapeutic efficacy in challenging anatomies. The research contributes to ongoing discussions about optimal revascularization strategies in complex PCI, particularly relevant as interventional cardiologists seek to minimize long-term stent-related adverse events. Understanding the three-year outcomes of these competing approaches helps inform treatment selection for high-complexity cases, potentially expanding the therapeutic armamentarium for interventional practitioners managing difficult coronary anatomy and reducing patient morbidity associated with permanent metallic implants.

The A-CLOSE trial, presented at ESC Congress 2026 and published simultaneously in NEJM, was a prospective randomized non-inferiority study evaluating antiplatelet strategies in high-ischaemic-risk patients one year after percutaneous coronary intervention with drug-eluting stents. Enrolling 3,203 patients across 19 centers between August 2019 and August 2023, the trial compared clopidogrel monotherapy against extended dual antiplatelet therapy (DAPT with aspirin and clopidogrel) for 24 months. Patients qualified for inclusion based on clinical high-risk features including acute coronary syndrome, diabetes, chronic kidney disease, or heart failure, alongside angiographic risk factors such as left main stem disease, bifurcation lesions, chronic total occlusions, and multivessel disease. The trial addresses an ongoing clinical debate regarding optimal antiplatelet strategies post-DAPT, as previous trials suggest clopidogrel monotherapy may reduce ischaemic events without increasing bleeding risk. This research matters because it provides evidence to guide treatment decisions balancing ischaemic protection against hemorrhagic complications in vulnerable patient populations following coronary intervention.

A drug-coated balloon (DCB) strategy has become an established option for de novo coronary lesions, offering the advantage of avoiding permanent implants. However, very long-term vascular changes after stentless percutaneous coronary intervention (PCI) remain insufficiently characterized. We report a case of chronic total occlusion that developed eight years after DCB angioplasty for a diffuse long right coronary artery lesion in a patient with unstable angina.

More than two decades of clinical research have firmly established the role of drug-eluting stents (DES) in contemporary interventional cardiology. Randomized trials and long-term follow-up studies support the safety and efficacy of contemporary DES, particularly in reducing restenosis and repeat revascularization while maintaining a favorable safety profile. Continuous advancements in stent engineering, biomaterials, and drug-delivery technologies have driven the evolution of second -generation drug eluting stents. While clinicians and patients often seek the best drug eluting stent, treatment decisions should be guided by robust clinical evidence, individual patient characteristics, lesion complexity, and current evidence-based clinical practice guidelines.

Angiography-derived FFR-guided revascularization was noninferior to pressure wire–based FFR-guided strategy for determining revascularization in patients with stable coronary artery disease. This finding suggests that angiography-derived FFR may serve as a practical, wire-free alternative for physiologic guidance of coronary revascularization, warranting confirmation in larger outcome-driven trials. (PROVISION; UMIN000049230)

Percutaneous coronary intervention with stent placement, or PCI, is a minimally invasive catheter-based procedure that restores blood flow to narrowed or blocked coronary arteries without open-heart surgery. One of the most commonly performed cardiac procedures in the United States, PCI typically requires only a small puncture in the wrist or groin, enabling same-day or overnight discharge. The procedure addresses cholesterol plaque buildup that restricts blood flow, causing chest pressure, shortness of breath, and fatigue. During PCI, a thin catheter advances to the blockage site where a balloon inflates to compress plaque and widen the artery. A metal mesh stent is then deployed to maintain arterial patency. PCI is indicated for acute heart attacks, unstable or stable angina limiting daily activities, abnormal stress tests, and confirmed significant blockages. However, not all narrowings require intervention; pressure-wire measurements and intravascular imaging during catheterization help determine which lesions warrant treatment versus medication management. Performed in a cardiac catheterization laboratory under conscious sedation, the procedure is typically painless and offers substantial advantages over traditional open-heart surgery.