Selenium (Se), a vital trace element, plays a significant role in maintaining vascular health and may offer protective effects against atherosclerosis. Its actions are mediated through Se-dependent selenoenzymes and selenoproteins, which enhance antioxidant defense, modulate inflammatory responses, and promote autophagy. These processes collectively help prevent cellular senescence-a state associated with age-related vascular decline characterized by oxidative stress, DNA damage, pro-inflammatory activity, and endothelial dysfunction. Epidemiological evidence consistently shows that low Se status is associated with increased risk of atherosclerotic cardiovascular disease within a narrow concentration range. However, clinical trials have not demonstrated clear reductions in cardiovascular events or mortality with Se supplementation alone. Overall, current evidence indicates that Se modulates key mechanisms involved in vascular aging and atherosclerosis, particularly redox balance, immune activation, and vascular cell homeostasis. This comprehensive review summarizes current epidemiological, clinical, and experimental research on the role of Se in cardiovascular health. It underscores Se's potential as a promising strategy for the prevention and treatment of atherosclerosis, while also acknowledging the complexities and nuances of its effects on vascular health. A deeper understanding of the cellular and molecular mechanisms involved could pave the way for targeted interventions aimed at reducing the burden of atherosclerotic cardiovascular disease.
Retinopathy of prematurity (ROP)-associated vision loss is driven by pathological retinal angiogenesis. Current therapies suppress neovascularization but do not fully restore vascular integrity or prevent long-term visual deficit. Activation of the sigma-1 receptor (Sig1R) has been reported to confer neuroprotection, yet its role in retinal vascular protection remains largely unexplored. Here, we investigated whether Sig1R activation confers vascular protection in experimental ROP. The oxygen-induced retinopathy (OIR) mouse model was induced in wild-type and Sig1R-/- mice with or without systemic (+)-pentazocine ([+]-PTZ) administration to activate Sig1R. Retinal vascular pathology, barrier integrity, and avascular areas were evaluated by fluorescein angiography and retinal flatmount analysis. Molecular changes in metabolic, oxidative, and inflammatory pathways were assessed by immunostaining/blotting and ELISA assay. Sig1R expression was reduced in OIR retinas, accompanied by decreased cullin-3 ubiquitin ligase (Cul3) and phosphorylated AMP-activated protein kinase (pAMPK) and increased pAkt and endothelial nitric oxide synthase (eNOS), indicative of metabolic and endothelial stress. Activation of Sig1R with (+)-PTZ restored Sig1R, Cul3, and pAMPK levels, suppressed pAkt/eNOS signaling, reduced oxidative stress, and attenuated Müller glial activation. OIR-induced upregulation of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and pro-angiogenic/inflammatory mediators, including vascular endothelial growth factor (VEGF), IL-6, TNF-α, macrophage colony-stimulating factor (M-CSF), vascular cell adhesion molecule 1 (VCAM-1), and tumor necrosis factor receptor (TNFR), were markedly reduced by (+)-PTZ. Functionally, Sig1R activation improved retinal vascular barrier integrity, reduced arterial tortuosity and pathological neovascularization, and promoted revascularization of avascular retina. Importantly, (+)-PTZ treatment failed to confer any vascular benefit in Sig1R-/- mice, confirming that these vascular benefits are Sig1R dependent. Sig1R activation preserves vascular integrity and suppresses pathological angiogenesis in OIR. Together with known neuroprotective effects, Sig1R represents a promising dual neurovascular therapeutic target for ROP.
Cardiovascular diseases (CVDs) remain the leading global cause of morbidity and mortality, imposing an increasing clinical and socioeconomic burden. Despite significant therapeutic advances, optimal control of risk factors and long-term outcomes remain challenging, particularly in patients with complex comorbidities. This narrative review provides a comprehensive and up-to-date synthesis of pharmacological options across major cardiovascular domains, with a specific focus on hypertension, heart failure, arrhythmias, and hypertrophic cardiomyopathy, conditions in which hemodynamic, neurohormonal, and electrophysiological pathways play central roles. We summarize mechanisms of action, clinical evidence, safety profiles, and guideline-based indications of established therapies, highlighting their relevance to vascular tone regulation, neurohormonal modulation, endothelial signaling, and myocardial function, the mechanistic axes that intersect with pathways implicated in pulmonary vascular disease (PVD). In addition, we discuss emerging therapeutic targets and innovative agents such as renin-angiotensin-aldosterone system silencers, endothelin pathway modulators, SGLT2 inhibitors, soluble guanylate cyclase stimulators, myosin inhibitors, and other mechanism-based approaches. Current challenges and unmet clinical needs are examined in the context of translational relevance for PVD and the broader goal of advancing individualized pharmacotherapy. Continued therapeutic innovation targeting shared vascular, metabolic, and neurohormonal pathways holds promise for improving outcomes across both systemic and pulmonary vascular diseases.
Cerebral cavernous malformations (CCMs) are characterized by abnormal clusters of dilated, thin-walled capillaries in the brain that are prone to bleeding, which give rise to a range of neurological symptoms including seizures and stroke. Current therapeutic strategies are restricted to surgical resection, highlighting the requirement for effective and efficient treatments. In this study, we investigated the therapeutic potential of Compound Danshen Dripping Pills (CDDP) as a traditional Chinese medicine (TCM) against the progression of CCMs. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to characterize the chemical composition of CDDP and identify its brain-penetrating ingredients. Lesion burden was assessed by macroscopic observation, micro-computed tomography (microCT), and histological analysis. Vascular integrity and function were evaluated by immunofluorescence staining. Blood flow was assessed by laser speckle contrast imaging and permeability was examined using Evans blue dye and FITC-dextran. Multi-omics approaches, including RNA sequencing (RNA-seq), proteomics, and metabolomics, were conducted to decipher molecular mechanisms. Western blot and quantitative Real-time PCR (qPCR) were performed to detect key signaling pathways. Brain-penetrating components were identified by UPLC-MS/MS, followed by molecular docking and molecular dynamics simulations for target proteins (MEKK3 and NF-κB). Surface plasmon resonance (SPR) assay was performed to validate the direct binding affinity of the identified key components to their respective target proteins. The functional impacts of target binding were assessed in HEK293T cells overexpressing MEKK3 (HEK293T/MEKK3-OE) by examining the phosphorylation levels of downstream mediators. KRIT1-knockdown human cerebral microvascular endothelial cells (HCMEC/D3) stimulated by lipopolysaccharide (LPS) were treated with identified components (ginsenoside F3 and tanshinone I), and assessed for trans-endothelial electrical resistance (TEER) and expression of critical inflammatory cytokines. UPLC-MS/MS identified 36 ingredients in CDDP, including phenolic acids, alkaloids, and ginsenosides. CDDP treatment dose-dependently reduced CCM lesion burden in Krit1iECKO mice, with 0.2 g/kg demonstrating optimal efficacy comparable to propranolol. Immunofluorescence revealed that CDDP significantly enhanced vascular integrity by upregulating Claudin-5 and VE-cadherin expression, increasing pericyte coverage, and normalizing basement membrane support. Functional assays demonstrated that CDDP restored cerebral blood flow and reduced vascular permeability. Integrated transcriptomics, proteomics, and metabolomics analysis revealed that CDDP significantly downregulated the MEKK3-MEK5-ERK5-KLF2/4-p-MLC2 signaling axis and suppressed inflammatory networks involving NF-κB, ICAM1, VCAM1, IL-6, IL-1β, and neutrophil extracellular traps (CitH3). Diprovocim-induced exacerbation of CCM lesions was effectively reversed by CDDP, confirming the involvement of MAPK and NF-κB pathways. Brain tissue analysis identified 11 brain-penetrating components, including salvianolic acids and ginsenosides. Molecular docking and molecular dynamics simulations revealed that ginsenoside F3 exhibited optimal binding affinity with NF-κB, while tanshinone I strongly bound to MEKK3. SPR assay further confirmed the direct binding, with ginsenoside F3 binding to NF-κB and tanshinone I binding to MEKK3. Functional validation in HEK293T/MEKK3-OE cells demonstrated that tanshinone I markedly suppressed MEKK3-driven phosphorylation of MEK5 and ERK5, while ginsenoside F3 significantly attenuated NF-κB phosphorylation. Administration of ginsenoside F3, tanshinone I, or their combination in Krit1iECKO mice led to reductions in cerebellar hemorrhagic lesions and vascular leakage, with the combination group exhibiting the most prominent therapeutic effect. In vitro validation in KRIT1-knockdown HCMEC/D3 cells demonstrated that ginsenoside F3, tanshinone I, and their combination significantly restored TEER values and reduced IL-1β and IL-6 expression, with the combination showing synergistic effects. CDDP exerts therapeutic effects against CCM progression by strengthening vascular integrity, restoring endothelial barrier function, and suppressing inflammation through inhibition of the MEKK3-MEK5-ERK5-KLF2/4-p-MLC2 and NF-κB signaling pathways. Brain-penetrating components, particularly ginsenoside F3 and tanshinone I, directly targeted key proteins (NF-κB and MEKK3) and synergistically protected endothelial function. These findings provide preclinical evidence supporting CDDP as a promising multi-target therapeutic strategy for CCMs.
The circadian system is an important regulator of cardiovascular immune homeostasis. Emerging evidence suggests that daily timing of immune responses may influence cardiovascular disease progression by coordinating leukocyte trafficking, inflammatory thresholds, metabolic adaptation, and tissue repair across the 24-hour cycle. This review examines how core and auxiliary circadian regulators, including BMAL1, CLOCK, PER/CRY complexes, REV-ERBs, RORs, and systemic timing cues, shape immune-cell activation through transcriptional, epigenetic, metabolic, and neuroendocrine mechanisms. We further synthesize evidence on circadian coordination of leukocyte trafficking, particularly the CXCL12/CXCR4 axis, and discuss how disrupted timing may promote inappropriate leukocyte recruitment into the vascular wall. At the cellular level, circadian misalignment has been associated with altered macrophage polarization, inflammasome activation, and inflammatory injury, processes that may modulate atherosclerosis, myocardial ischemia-reperfusion injury, and post-infarction remodeling. Finally, we evaluate the translational potential and current limitations of chronopharmacology, emphasizing that time-of-day treatment strategies require careful consideration of clinical evidence, circadian phase assessment, chronotype, sex, age, comorbidities, and treatment feasibility. This evidence-weighted chrono-immunological perspective may help refine future research on cardiovascular inflammation and inform the development of more individualized prevention and therapeutic strategies.
High-phenolic extra-virgin olive oil (EVOO) is a chemically dynamic bioactive matrix in which cultivar, ripening stage, processing, storage, and digestion shape the final profile of phenolic alcohols and secoiridoids. In inflammatory bowel disease (IBD), chronic intestinal inflammation is associated with barrier dysfunction, dysbiosis, systemic immune activation, endothelial injury, platelet hyperreactivity, and increased cardiovascular risk. This narrative review evaluates whether EVOO phenolics may intersect the gut-endothelium-platelet axis linking IBD to vascular and thromboinflammatory complications. The review focuses on hydroxytyrosol, tyrosol, oleuropein- and ligstroside-derived secoiridoids, oleocanthal, and oleacein, with emphasis on their biosynthetic origin, processing-driven transformations, bioavailability, metabolism, and biological targets. Current evidence supports plausible effects on epithelial barrier integrity, TLR4/NF-κB signalling, Nrf2-mediated antioxidant defence, oxidised LDL formation, endothelial activation, and platelet-related pathways. Nevertheless, direct clinical evidence in IBD patients remains limited, and most cardiovascular-relevant findings are extrapolated from non-IBD human trials, animal studies, or in vitro models. Chemically characterised, biomarker-anchored intervention trials are needed before high-phenolic EVOO can be considered a validated strategy for modifying cardiovascular risk in IBD.
Vascular malformations, including arteriovenous malformations (AVMs), venous malformations (VMs), and lymphatic malformations (LMs), carry a risk of rupture, bleeding, and significant morbidity. AVMs are high-flow lesions associated with abnormal shunting between arteries and veins, while VMs and LMs are low-flow malformations characterized by dilated venous or lymphatic channels. Current therapeutic options are limited, which often results in mental health issues and diminished quality of life, particularly in younger patients. Sclerotherapy with ethanol-based agents is an effective minimally invasive treatment, particularly for low-flow lesions. Injectable ethyl cellulose-based gels containing ethanol have emerged as a potential treatment for sclerosing these abnormal vessels; however, their exact mechanism of action and behavior within the vasculature remain inadequately understood. Comprehensive knowledge of the therapeutic mechanism is crucial for optimizing its clinical application and achieving the best treatment outcomes. In this study, we explored the production process, stability, and intravascular behavior of ethanol-based gels, providing essential information for clinical practice and patient care. We developed an injection model to elucidate the physical properties and dynamics of the gel under flow conditions in vitro and within blood vessels in ovo. Our results demonstrate an effective and safe injection, showing limited adverse effects. These insights contribute to advancing injectable polymer-based gel formulations, offering improved options for treating vascular malformations.
Hypertriglyceridemia can increase the risk of acute pancreatitis and atherosclerotic cardiovascular disease (ASCVD). Patients with familial chylomicronemia syndrome are at an even higher risk of developing pancreatitis due to elevated triglycerides. A pathway involving small interfering RNA that selectively inhibits apolipoprotein C-III (APOC3) messenger RNA through RNA interference is currently being studied to reduce levels of apoC-III and thus, triglycerides. This review presents and discusses the current pharmacokinetic, pharmacodynamics, and clinical and scientific evidence pertaining to plozasiran, a small interfering RNA medicine.
Bradykinin is a nonapeptide of the kinin family with vasoactive and proinflammatory activities. While generation of kinins is mainly driven by activation of the contact system and plasma or tissue kallikreins, additional independent cascades contribute to their formation. Kinins mediate their effects through the constitutively expressed bradykinin B2 receptor and the inducible bradykinin B1 receptor. Bradykinin is the most studied kinin peptide mainly due to its potential role in the vascular system and exerts its effects mainly via the bradykinin B2 receptor. Kinins have been implicated in the pathogenesis of multiple types of angioedema as well as of various conditions, such as allergic mast cell-mediated skin diseases, cardiovascular and respiratory pathologies. This review summarizes our current knowledge of the biology, regulation, and functions of kinins and their receptors as well the emerging evidence on the various mechanisms involved in bradykinin formation and their relevance in disease pathogenesis. The review focuses on the clinical evidence on the roles of bradykinin and of the bradykinin B2 receptor in various conditions, and the potential to develop novel strategies targeting the bradykinin B2 receptor for management of bradykinin-mediated diseases.
Current treatments for choroidal neovascularization (CNV) and its associated subretinal fibrosis (SRF), major causes of vision loss, are limited by the need for frequent intravitreal injections and the emergence of drug resistance. This study evaluated the safety and efficacy of the intravitreal administration of engineered humanized anti-vascular endothelial growth factor Nanobodies, including a wild-type Nanobody (WHNb) and two mutated variants (MHNb136 and MHNb256), in a rat model of laser-induced CNV and associated SRF. Safety was assessed through in vivo electrophysiological and histopathological analyses following intravitreal injection of Nanobodies at doses of 12.5, 25, 50, and 100 µg. Efficacy was evaluated in rat models of laser-induced CNV and SRF using double immunohistochemistry for isolectin B4 and anti-collagen type I on sclerochoroidal flat mounts. Mean CNV and SRF areas in Nanobody-treated groups were compared with those in bevacizumab-treated and sham control groups. None of the Nanobodies showed retinal toxicity in safety assessments. Compared with bevacizumab, MHNb136 and MHNb256 reduced the CNV area by 1.72-fold and 1.8-fold, respectively (both p < 0.0001), whereas WHNb showed an effect nearly identical to that of bevacizumab. In addition, 12.5 µg MHNb136 and 100 µg MHNb256 reduced the SRF area by 1.3-fold (p = 0.047) and 1.6-fold (p = 0.0007), respectively, relative to bevacizumab. For CNV reduction, 12.5 µg MHNb136 was comparable to 25 µg MHNb256; both outperformed bevacizumab. For SRF reduction, 12.5 µg MHNb136 was more effective than bevacizumab and comparable to 100 µg MHNb256. These findings suggest that 12.5 µg MHNb136 may represent a cost-effective bioengineered Nanobody candidate for future clinical studies.
Diabetic retinopathy (DR) is a major cause of irreversible vision loss driven primarily by retinal vascular damage, yet its mechanisms remain incompletely understood. Here, we identify calnexin (Canx) as a critical suppressor of pathological angiogenesis in DR. We demonstrate that hyperglycemia synergizes with TNF-α to downregulate Canx in mouse retinal microvascular endothelial cells. This loss of Canx activates Nox4, leading to hyperactivation of the Ire1α/Xbp1s branch of the unfolded protein response. Consequently, endoplasmic reticulum stress is amplified, pathological Vegfa transcription is upregulated, and the inner blood-retinal barrier is disrupted. In streptozotocin-induced diabetic mouse models, Canx deficiency exacerbated endothelial dysfunction and retinal vascular pathology. Conversely, both adalimumab treatment and adeno-associated virus-mediated Canx overexpression in vivo suppressed the Nox4/Ire1α/Xbp1s/Vegfa cascade, significantly reduced vascular leakage and acellular capillary formation, attenuated retinal thinning, and normalized endothelial cell functions (proliferation, migration, tube formation). Collectively, our findings establish Canx as a key upstream regulator of Vegfa-mediated vascular injury in DR. Our study suggests that targeting Canx, either genetically or via repurposing adalimumab, represents a source-specific strategy to halt DR progression by blocking pathological Vegfa production at its origin. Diabetic retinopathy (DR) remains a leading cause of blindness, with current interventions often failing to halt progression. In mouse retinal microvascular endothelial cells (mRMVECs), hyperglycemia/tumor necrosis factor-α suppress calnexin (Canx). Canx downregulation drove vascular pathology in mRMVECs via the Nox4/Ire1α/Xbp1s pathway, amplifying endoplasmic reticulum stress and pathological Vegfa production. In streptozotocin-induced diabetic mouse models, Canx overexpression or adalimumab intervention attenuated DR in vivo by blocking this cascade. Our findings establish Canx as a critical upstream regulator, proposing Canx-targeted strategies as source-specific therapeutics for DR.
As cancer survival rates improve, the long-term burden of treatment has become increasingly evident. Cancer survivors face a markedly higher risk of cardiovascular-related complications and premature, non-cancer-related mortality. In particular, cardiovascular disease (CVD) is disproportionately prevalent, with survivors approximately 40% more likely to develop and die from CVD compared to the general population. Although this increased morbidity reflects both acute cardiotoxic events and the later development and progression of more chronic CVDs, traditionally viewed as direct consequences of cancer therapies, the underlying mechanisms, especially those that are feasible to modify, are poorly understood. Emerging evidence positions the gut-heart axis as a central regulator of cardiovascular risk in cardio-oncology. This avenue is especially compelling to explore as the gut microbiome is well documented to be altered by cancer therapies, including chemotherapy, immune checkpoint inhibitors, targeted therapies, and radiation, with profound and persistent changes in diversity, composition and function widely reported across clinical cohorts. Comparable microbial changes have been observed in non-cancer cohorts with cardiovascular disease. For example, specific microbial metabolites have been reported to exert cardiovascular protective benefits in hypertension. Thus, there is a compelling opportunity to explore the gut microbiome to advance our understanding and ability to prevent cardiovascular disease in cancer survivors. This review synthesises current evidence linking the gut microbiome to cancer therapy-related cardiac dysfunction (CTRCD), evaluates microbial metabolites as predictive biomarkers of cardiotoxicity, and discusses microbiome-targeted modulation as an emerging strategy for improving cardiovascular outcomes in cancer survivors.
Bone regeneration in oral and maxillofacial surgery (OMFS) remains challenging, particularly in procedures such as alveolar ridge preservation, sinus floor augmentation, mandibular reconstruction, and peri implant bone regeneration. Bioactive molecules have emerged as promising therapeutic agents that enhance osteogenesis, angiogenesis, and tissue remodeling through modulation of key cellular signaling pathways. A structured literature review was conducted using PubMed, Scopus, and Web of Science databases. The search primarily focused on studies published between 2020 and 2025 to capture recent advances, while incorporating foundational studies to support key biological mechanisms. Inclusion criteria comprised peer reviewed in in vitro, in vivo, and clinical studies investigating bioactive molecules and scaffold based bone regeneration strategies in OMFS. Bioactive molecules including icariin, bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), and dental pulp stem cell (DPSC) derived secretomes significantly enhance osteogenic differentiation, extracellular matrix mineralization, and angiogenesis. These effects are mediated through major signaling pathways such as BMP/Smad, MAPK/ERK, PI3K/Akt, and HIF-1α pathways. Integration with biomaterial scaffolds enables controlled spatiotemporal release, improving regenerative outcomes. However, translational challenges remain, including dose-dependent adverse effects (particularly with BMPs), suboptimal release kinetics, and limitations of current experimental models in replicating mandibular biomechanics. Bioactive molecule-based therapies represent a promising approach for enhancing bone regeneration in OMFS. Future advancements in nanotechnology-based delivery systems, three-dimensional bioprinting, and personalized regenerative strategies are essential to bridge the gap between experimental success and clinical application.
Work is a social determinant of Cardiovascular (CV) and general health and can both influence and be influenced by health. The type of work, working conditions, and work environment are fundamental social determinants of CV and general health status. Climate change presents an urgent and increasing threat to workers' health, via both direct exposure to environmental risks and the indirect worsening of social and health inequalities. Occupational health, which focuses on the promotion of mental and physical health and well-being of workers, and the avoidance of occupationrelated health risks, is a crucial but less discussed concern and component of human health. Relevant research at the intersection of climate change and occupational health remains scarce. Additionally, mitigation of climate change and adaptation efforts are driving forces for rapid transformations in the workplace, including shifts towards sustainability and circular economy models. These transitions are creating new occupational hazards, including those concerning renewable energy and the circular economy sectors. Investment in occupational health research and surveillance should be increased to address the evolving influences of both climate change and the green transition, to enhance and protect workers' CV and general health. Among the work-related factors that play an important role in patients with CVD, the following seem crucial: work participation, physical and mental work capability, appropriate work, support from and flexibility of the work environment, inter-personal communication, person-centered milieu, and interdisciplinary communication. A moderate leisure-time physical activity combined with moderate occupational physical activity may be a more plausible way to combine these two activities to sustain and/or improve CV health. Such an approach may be able to ameliorate workrelated outcomes in patients with CVD. Finally, lifestyle interventions targeting multiple behaviors are also most important to prevent CVD and attain cardiometabolic health. All these issues of occupational CVD are herein reviewed, and relevant meta-analyses are tabulated and discussed.
Aging is a relentless process of gradual physio-biochemical non-reversible deterioration that significantly influences human health, leading to declining cellular function and increasing cellular damage; it is recognized as a major risk factor for atherosclerosis and cardiovascular (CV) disease (CVD), the leading cause of death worldwide. Although aging is inevitable, healthy aging is the key to well-being. Longevity is a desirable yet complex outcome influenced by a wide range of factors, including genetics, lifestyle choices, healthcare access, socio-economic conditions, and other environmental factors. The compromised efficiency of processes that counteract age-associated molecular damage affects CVD susceptibility and expedites the emergence of clinical disease. Recently recognized key resilience mechanisms related to aging may constitute new potential therapeutic targets. Geroscience focuses on the discovery and translation of methods and interventions to curtail or reverse age-related deficits that compromise quality of life for older individuals. The geroscience paradigm, increasingly acknowledged in medical specialties, renders possible the prevention of premature aging, the optimal treatment of geriatric diseases, the reduction of healthcare disparities and prejudices, and the extension of the population's health span. These important geroscience issues, including multimorbidity, frailty, tendency to frequent falls, cognitive and multisensory impairment, cardiac arrhythmias, coronary disease and heart failure, as well as undernutrition, sarcopenia and polypharmacy, are herein discussed, together with recent relevant medical advances. Emphasis is placed on boosting psychology and also on pharmacological and nonpharmacological interventions such as exercise and physical activity, healthy diets and lifestyle that target key components of aging, which might assist in both primary (geroprotection) and secondary prevention (gerotherapeutics) of CV and other diseases posing an enormous challenge in older age. The geroscience paradigm is increasingly recognized in medical specialties, enabling the prevention of premature aging, optimal management of geriatric ailments, reduction of health-care disparities and prejudices, and potential improvement of the population's health-span.
Arterial catheters (ACs) are essential devices widely used for hemodynamic monitoring and blood sampling. Whilst their infectious risk is well-known, the surveillance and identification of arterial catheter-related bloodstream infections (AC-CRBSI) remains underappreciated, and guidelines recommending best practices to prevent infection are few and inconsistent. Most evidence for AC infection prevention is inferred from studies focused on central venous catheter infection prevention. Few studies have directly explored optimal infection prevention strategies for ACs. For AC-CRBSI prevention, several strategies are valuable during insertion and maintenance of the catheter: minimisation of catheter-days by appropriate catheter stewardship, procedural training of providers, standardisation of insertion packs to promote adherence to an insertion bundle, cutaneous antisepsis with an alcohol-based 2% chlorhexidine solution during insertion and maintenance, chlorhexidine impregnated dressings, change of dressing every 7 days unless visibly disrupted or soiled, hand hygiene, disinfection of the access port and change of administration sets every 7 days. Other interventions to prevent AC-CRBSI are more controversial and necessitate further research such as the choice of the insertion site (femoral vs. radial), the type of sterile barrier precautions and their cost effectiveness, the infectious risk related to ultrasound guidance, the optimal catheter securement device, the utility of needleless connectors and closed loop blood sampling systems and the effectiveness of scheduled catheter changes. Arterial catheters demonstrate an ongoing risk of contamination throughout their lifespan, from insertion to removal. A comprehensive prevention strategy should address the entire arterial catheter lifecycle and is most effective when implemented as a bundled approach. This review summarises current knowledge on AC-CRBSI prevention during the entire lifecycle of the catheter and identifies priorities for future research.
The article presents the results of a structured literature review of the past decade and focuses on the crucial role of platelets in the pathogenesis of pulmonary arterial hypertension (PAH). It explores how endothelial dysfunction initiates early prothrombotic signals that activate platelets, which, in response, adopt a pro-inflammatory phenotype, release cytokines and chemokines, and form aggregates with leukocytes, thereby modulating their migration and activity. A key feature of PAH is the "platelet paradox," in which chronic in vivo activation coexists with reduced ex vivo reactivity due to functional exhaustion. Prolonged stimulation and disease progression lead to complex hemostatic dysregulation, characterized by heterogeneity in platelet phenotypes. At the same time, platelets undergo immunometabolic reprogramming, with a predominance of glycolysis, over oxidative phosphorylation, mitochondrial dysfunction, altered fatty acid oxidation (FAO), increased lactate production, and enhanced vesicle release. These phenomena sustain inflammation and promote pulmonary vascular remodeling. This study aims to review the current mechanisms of immunometabolic platelet activation in pulmonary arterial hypertension. It primarily focuses on platelet aspects as key elements in disease progression and as potential sources of new biomarkers and therapeutic targets.
Mastocytosis is a neoplasm characterised by clonal proliferation of mast cells (MCs) in the skin and other organs, including the heart, and symptoms produced by MC-derived mediators. MC activation syndrome (MCAS) relates to increased and inappropriate activation of MCs without clonal proliferation. Mast cells are tissue-resident immune cells strategically located in different cardiac sites, e.g., myocardium, pericardium, aortic valve, and close to nerves, and in atherosclerotic plaques. The mediators (e.g., histamine, tryptase, chymase, cytokines, and chemokines) have roles in inflammation, angiogenesis, tissue remodelling, and fibrosis. They activate different cardiac resident immune cells (e.g., macrophages) and structural cells (e.g., fibroblasts and endothelial cells). MCs participate in atherosclerosis and several cardiovascular diseases (CVD), comprising allergic angina, coronary syndromes, and arrhythmias, by destabilizing and promoting atherosclerotic plaque rupture with its attendant dire consequences. Furthermore, MCs stimulate fibrosis after a myocardial infarction. MCAS is increasingly appreciated as it affects many patients previously noted to have various apparently idiopathic chronic multisystem inflammatory and/or allergic diseases or dystrophisms. Symptoms resulting from mediator release comprise flushing, hypotension, urticaria, angioedema, headache, vomiting, and diarrhea. Diagnosis is rendered by skin and/or bone marrow biopsy. Considering the increasing incidence and prevalence of MC-related diseases, guidance is needed for clinicians or researchers to select efficacious MC stabilizers that could block external stimulus signals into cells, inhibit intracellular signalling pathways, and disrupt degranulation. These novel therapies may soon find their way into the clinical arena. All relevant data and important advances in this recently recognized clinical entity are herein reviewed.
Sex-related differences in microvascular reactivity may be influenced by the magnitude of muscle desaturation (ischemic stimulus) during the blood flow occlusion period. Thus, this study used near-infrared spectroscopy (NIRS) to assess skeletal muscle microvascular reactivity in three distinct metabolic and mechanical conditions. Nineteen participants (10 males, 9 females) completed a randomized parallel design including a vascular occlusion test (VOT), maximal voluntary isometric contraction (MVIC), and a dynamic fatigue exercise protocol (FEx) to elicit ischemic, mechanic and metabolic insults, respectively. Morphological muscle quality was also assessed using ultrasonography. NIRS-derived indices of tissue oxygenation and blood volume were continuously monitored. Males exhibited a greater post-exercise total hemoglobin reperfusion slope ([tHb] slope) across protocols compared with females (p < 0.05). In males, higher morphological muscle quality was associated with a steeper reperfusion slope (p < 0.05), whereas no such relationships were observed in females. Sex differences in microvascular reactivity were evident across ischemic, isometric, and dynamic exercise conditions, with oxygen extraction only partially accounting for sex differences in microvascular reactivity in highly metabolic demand condition such as FEx. Our findings also suggest that the greater microvascular reactivity in males may be linked to better morphological muscle quality compared to females, thus providing novel insights into the mechanisms driving the accelerated reperfusion rates observed in males compared to females.
Large conductance calcium-activated potassium channels (BKCa) play an important role in the regulation of vascular tone. However, the properties of BKCa channels in smooth muscle of pulmonary arteries are poorly understood. Previous experimental studies demonstrated that pulmonary hypoxic vasoconstriction as a normal physiological response to decreased oxygen levels was impaired in diabetic animals due to abnormal activation of BKCa channels. The aim of this study was to identify mechanisms of diabetes-induced activation of BKCa channels in freshly isolated smooth muscle cells from rat pulmonary arteries. Type 1 diabetes was induced by streptozotocin (STZ). Whole-cell potassium currents were recorded using the patch-clamp method. Expression levels of BK-α and BK-β1 subunits were measured by real-time PCR. Our results demonstrate that the amplitude of whole-cell current through BKCa channels in rat pulmonary artery smooth muscle cells is significantly increased during STZ-induced diabetes without altering the expression of BK-α and BK-β1 subunits and channel calcium sensitivity. The slow component of BKCa current deactivation time constant and spontaneous transient outward current amplitude were increased in diabetic animals compared to healthy animals. We conclude that abnormal activation of the BKCa channel in pulmonary arterial smooth muscle during diabetes is associated with alterations in the local control mechanism of the BKCa pore-gate domain.