Endothelial Microparticles Research Articles

Predictors of 1-year follow-up period MACE in patients with NSTEMI

Abstract Background Identifying viable predictors of MACE in NSTEMI continues to pose a challenge in the field of cardiology. Unraveling these factors will elucidate crucial mechanisms underlying adverse post-infarction outcomes and identify key strategies for optimizing treatment. Aim Evaluation by using the multi-marker panel the biomarkers having a high predictive value regarding the risk of MACE developing in patients with NSTEMI. Methods The study embraced 550 patients with NSTEMI treated by angioplasty. A panel of 67 biomarkers was quantitatively determined by ELISA, immune assay and flow cytometry on admission in the blood linked to the most important mechanisms conceptually involved in post-infarction evolution (inflammation, endothelial dysfunction, hemostasis disorders, oxidative stress, NETosis, Ang 1-7/Ang II axis etc.) The rate of MACE (cardiac death, stroke, myocardial reinfarction) was estimated in a follow-up period of 18 months. In order to underline the overt predictors, the hazard ratio CI (95%) was assayed. 60 healthy persona formed control series. Results Upon admission, the circulating levels of 62 out of 67 biomarkers in patients with NSTEMI significantly deviated from control values. The MACE rate during 1-st year after revascularization was 28% (154 pts). According to hazard ratio (HR) the maximal predictive power regarding MACE risk of 1-year follow-up period was unraveled for 3 markers: endothelial microparticles (EMs), platelet-derived microvesicles (PMVs) and von Willebrand/ADAMTS13 ratio. For EMs – HR 2.21 CI (1.19-3.84; p<0.01); for PMVs - HR 2.56 CI (1.43-3.96; p<0.01); for von Willebrand/ADAMTS13 ratio - HR 2.94 CI (1.77-4.73; p<0.01). EMs-CD62E exceeded control level by 77,6% (325.6±101.5 vs 183.2±67.7 Ms/µL); PMVs-CD62P by 129% (378.6±87.4 vs 165.5±59.6 MVs/µL) and von Willebrand/ADAMTS13 ratio by 88% (2.52±1.88 vs 1.34±1.11). These predictors have not been adjusted to age, gender and cardiovascular risk factors. Conclusion Considering the pathophysiological significance of the highlighted predictors of MACE (EMs, PMPs and the von Willebrand/ADAMTS13 ratio) endothelial dysfunction and an activated prothrombotic state emerge as pivotal mechanism in the adverse progression of NSTEMI. THUS, these predictors should indicate a focus on corrective therspy targets.

SGLT2 Inhibitor Ameliorates Smooth-Muscle Cell Proliferation via Endothelial Microparticles Stimulated by Indoxyl Sulfate

SGLT2 Inhibitor Ameliorates Smooth-Muscle Cell Proliferation via Endothelial Microparticles Stimulated by Indoxyl Sulfate

Effects of human brain microvascular endothelial cell membrane microparticles on blood-brain barrier during hypoxia and its molecular mechanism.

Effects of human brain microvascular endothelial cell membrane microparticles on blood-brain barrier during hypoxia and its molecular mechanism.

Association between endothelial microparticles and objectively measured physical activity in adults with obesity

BackgroundCardiovascular disease (CVD) is a serious global public health concern that often originates from endothelial dysfunction. Microparticles (MPs) can reflect alterations in tissue or cell function phenotype and responsiveness under various physiological and pathological conditions. MPs derived from endothelial cells may serve as potential biomarkers for CVD. We investigated the association between endothelial-derived MPs (EMPs) and objectively measured physical activity (PA) in adults with obesity and their potential correlation with inflammatory and cardiometabolic biomarkers. MethodsThis cross-sectional study included 50 participants, whose daily movement behaviors were evaluated using activPAL™, which measures moderate-to-vigorous intensity PA (MVPA), light PA (LPA), and standing time. The MP sub-populations were separated from platelet-poor plasma, incubated with multiple antibodies, and analyzed using multi-color flow cytometry. Cytokines, interleukin (IL)−1β, IL-8, E-selectin, P-selectin, and intercellular adhesion molecules (ICAMs), were measured using a customized Luminex® assay kit. Pearson’s correlation coefficients were used to examine associations. ResultsMVPA was associated with lower expressions of ICAM and E-selectin in EMPs, whereas standing time was associated with a higher expression of E-selectin. A positive association exists between leukocyte-derived MP percentage and P-selectin levels in EMPs and E-selectin levels in the plasma. In addition, higher plasma P-selectin level was associated with higher P- and E-selectin levels in EMPs, as was higher inflammation (IL-1β and IL-8). ConclusionThe MPs were negatively associated with MVPA and positively associated with standing time in the participants with obesity. These results underscore the importance of promoting PA interventions, especially at moderate-to-vigorous intensities. Further longitudinal and interventional studies are warranted to elucidate the dynamic interplay among PA, MPs, and endothelial function.

The Role and Mechanism of Vascular Aging in Geriatric Vascular Diseases.

Vascular aging is the pathological basis for the aging of various organ systems in the human body and is a common pathogenesis leading to the development of atherosclerosis, Alzheimer's disease, and other conditions among older adults. Aging is characterized by accelerated pulse wave velocity, thickening of the carotid artery intima-media, and decreased vascular dilation function. Signaling pathways such as mTOR, AMPK, NF-κB, Klotho, SIRT, and other key proteins are likely involved in these processes. The detection of biomarkers related to vascular aging, including senescence-associated β-galactosidase, endothelial progenitor cells, circulating endothelial microparticles, and exosomal miRNAs, aids in assessing vascular status and prognosis. Repairing endothelial injury, reducing oxidative stress-inflammatory responses, and restoring mitochondrial and telomere functions are reliable measures to counter vascular aging. In summary, research on vascular aging is the driving force that will provide rational strategies to intervene in geriatric vascular diseases and achieve the long-term goal of healthy aging.

Effects of exosomes and inflammatory response on tumor: a bibliometrics study and visualization analysis via CiteSpace and VOSviewer

BackgroundTumor is a new organism formed by abnormal hyperplasia of local tissue cells under the action of various tumorigenic factors. Inflammation plays a decisive role in inducing tumorigenesis, promoting tumor development, invasion and migration. More and more evidence indicate that exosomes are involved in regulating the formation of tumor microenvironment in the process of proinflammatory carcinogenesis, leading to the stimulation of anti-tumor immune response or systemic immunosuppression, and exosomes play a crucial role in the development of tumor.MethodsThe articles on tumor-derived exosomes and inflammatory responses from January 2005 to January 2024 were collected through Web of Science (WOS), and the inclusion criteria were “Article”, “Review Article” and “Early Access”. Articles obtained after excluding “Book Chapters”, “Editorial Material”, “Proceeding Paper”, “Meeting ” and “Retracted Publication”. Bibliometrics and visualization analysis were carried out on the obtained articles using CiteSpace6.2.R6 and VOSviewer1.6.20.ResultsTotal of 703 articles were included. The number of published documents showed a fluctuating growth trend year by year. A total of 61 countries have participated in the research on the effects of exosomes and inflammatory responses on tumors, among which China and the United States have the largest influence in this field. The obtained articles have been published in 60 journals around the world, among which PLOS ONE and NAT REV IMMUNOL are the journals with the most published articles and the highest co-citations respectively. The article from French author THERY C was cited the most (202 times). As a major researcher on the basic function of exosomes, THERY C established the gold standard for extraction, separation and identification of exosomes, and found that exosomes promote tumor metastasis through direct regulation of miRNA. Her research has had a huge impact on the field. Keyword co-occurrence analysis indicate that extracellular vesicles, inflammation, cancer, miRNAs, mesenchymal stem cells, drug delivery, gastric cancer and circulating endothelial microparticles are the research hotspot at present stage. The main keywords of the cluster analysis show that extracellular vesicles, human papilloma virus, myeloid cells, tumor macro-environment are the current research hotspots and frontier. The research hotspots have developed over time from the time chart of keywords and clustering, especially after 2016, exosomes have established extensive links with drug delivery, cancer treatment, inflammatory response and other fields. Tumor-derived exosomes stimulate receptor cells to secrete pro-inflammatory cytokines and growth factors, enabling immune and inflammatory cells to perceive the intracellular environment of cancer cells even when cancer cells do not express any tumor-specific antigens. For example, in anoxic environment, cancer cells can secrete exosomes containing pro-inflammatory factors to promote the invasion and metastasis of cancer cells. In the complex tumor microenvironment, both tumor cells and various stromal cells will secrete specific exosomes, and promote the development of tumors through various ways, so that tumor cells have drug resistance, and bring adverse effects on the clinical treatment of tumor patients. MicroRNAs and long noncoding RNA as hot keywords play important roles in regulating and mediating tumor development, and their specificity makes them important biomarkers for cancer prediction and diagnosis. Highlighting word analysis shows that microRNAs secreted by leukemia patients can effectively promote the proliferation of malignant cells and the development of cardiovascular diseases. At the same time, exosomes can induce the secretion of some microRNAs in patients, leading to cardiac repair and regeneration. Therefore, the detection and screening of microRNAs plays a crucial role in predicting the incidence of cardiovascular diseases in patients.ConclusionExosomes have attracted increasing attention due to their significant heterogeneity and ability to regulate the tumor immune microenvironment. However, tumor cell-derived exosomes accelerate tumor progression by enhancing immunosuppression and inflammation, increasing oxidative stress, and promoting angiogenesis, which may lead to poor prognosis.Graphical abstract

High-volume hemofiltration does not protect human kidney endothelial and tubular epithelial cells from septic plasma-induced injury

High volume hemofiltration (HVHF) could remove from plasma inflammatory mediators involved in sepsis-associated acute kidney injury (SA-AKI). The IVOIRE trial did not show improvements of outcome and organ dysfunction using HVHF. The aim of this study was to evaluate in vitro the biological effects of plasma of patients treated by HVHF or standard volume hemofiltration (SVHF). We evaluated leukocyte adhesion, apoptosis and functional alterations of endothelial cells (EC) and tubular epithelial cells (TEC). In vitro data were correlated with plasma levels of TNF-α, Fas-Ligand (FasL), CD40-Ligand (CD40L), von Willebrand Factor (vWF) and endothelial-derived microparticles. An experimental model of in vitro hemofiltration using LPS-activated blood was established to assess cytokine mass adsorption during HVHF or SVHF. Plasma concentrations of TNF-ɑ, FasL, CD40L and von Willebrand Factor (vWF) were elevated at the start (d1h0) of both HVHF and SVHF, significantly decreased after 6 h (d1h6), remained stable after 12 h (d1h12) and then newly increased at 48 h (d3h0). Plasma levels of all these molecules were similar between HVHF- and SVHF-treated patients at all time points considered. In addition, the levels of endothelial microparticles remained always elevated, suggesting the presence of a persistent microvascular injury. Plasma from septic patients induced leukocyte adhesion on EC and TEC through up-regulation of adhesion receptors. Moreover, on EC, septic plasma induced a cytotoxic and anti-angiogenic effect. On TEC, septic plasma exerted a direct pro-apoptotic effect via Fas up-regulation and caspase activation, loss of polarity, altered expression of megalin and tight junction molecules with an impaired ability to internalize albumin. The inhibition of plasma-induced cell injury was concomitant to the decrease of TNF-α, Fas-Ligand and CD40-Ligand levels. The protective effect of both HVHF and SVHF was time-limited, since a further increase of circulating mediators and plasma-induced cell injury was observed after 48 h (d3h0). No significant difference of EC/TEC damage were observed using HVHF- or SVHF-treated plasma. The in vitro hemofiltration model confirmed the absence of a significant modulation of cytokine adsorption between HVHF and SVHF. In comparison to SVHF, HVHF did not increase inflammatory cytokine clearance and did not reverse the detrimental effects of septic plasma-induced EC and TEC injury. Further studies using adsorptive membranes are needed to evaluate the potential role of high dose convective therapies in the limitation of the harmful activity of plasma soluble factors involved in SA-AKI.Trial registration IVOIRE randomized clinical trial; ClinicalTrials.gov (NCT00241228) (18/10/2005).

The Future of Kawasaki Disease Diagnosis: Liquid Biopsy May Hold the Key.

Kawasaki disease (KD) is a febrile illness characterised by systemic inflammation of small- and medium-sized blood vessels, which commonly occurs in young children. Although self-limiting, there is a risk of developing coronary artery lesions as the disease progresses, with delay in diagnosis and treatment. Unfortunately, the diagnosis of KD continues to remain a clinical dilemma. Thus, this article not only summarises the key research gaps associated with KD, but also evaluates the possibility of using circulating endothelial injury biomarkers, such as circulating endothelial cells, endothelial microparticles and vascular endothelial cell-free DNA, as diagnostic and prognostic tools for KD: a "liquid biopsy" approach. The challenges of translating liquid biopsies to use in KD and the opportunities for improvement in its diagnosis and management that such translation may provide are discussed. The use of endothelial damage markers, which are easily obtained via blood collection, as diagnostic tools is promising, and we hope this will be translated to clinical applications in the near future.

Novel Biomarkers in Vascular Diseases: From Discovery to Clinical Translation

Endothelial activation as well as dysfunction is a major factor in atherosclerosis, cardiovascular disorders, and cardiorenal syndrome. Endothelial dysfunction is additionally associated with metabolic syndrome as well as type II diabetes. The hunt for distinctive as well as sensitive biomarkers of endothelial activity and dysfunction may have substantial therapeutic consequences. This review pinpoints the variations in biomarkers that occur between endothelial activation and endothelial dysfunction in cardiovascular illnesses, and then briefly highlights the most significant biomarkers of endothelial activation. Biomarkers of endothelial activation consist of endothelial adhesion molecules, as well as cytokines, and C-reactive protein, along with CD62E++/E-selectin activated endothelial microparticles, and oxidation of low-density lipoproteins, together with asymmetric dimethylarginine as well as endocan. This study also includes an update on the new biomarkers of endothelial dysfunction, such as matrix metalloproteinases (MMP) (e.g., MMP-7, MMP-9), along with ANGPTL2, and endoglin, together with annexin V++ endothelium apoptotic microparticles, and serum homocysteine. Finally, this study stresses the limits of biomarkers of endothelium activation and dysfunction in clinical situations.

MACE prediction in patients with STEMI and NSTEMI: from classic to novel markers in the estimation of coronary microcirculation disorder

Evaluation of classic and novel markers of coronary microcirculatory disorder (CMD) which have a predictive value on the risk of major cardiovascular event (MACE) in patients with STEMI and NSTEMI. Material and methods. The research included the retrospective analysis of a prospective observational study carried out on 600 patients, of which have been formed equal 4 groups of 80 patients (STEMI+MACE; STEMI-MACE; NSTEMI+MACE; NSTEMI-MACE) in which the collected blood on the 5-th day after angioplasty, the circulating level of 16 markers referring to CMD in the field of estimating endothelial dysfunction and hemostasis was determined: 8 classic markers (hsCRP, IL-6, TNF-α, IL-10, myeloperoxidase, NO , angiopoietin 2, fibrin monomers) and 8 new markers (neopteirn, endocan, syndecan 1, L-Arginine/ADMA, Ang 1-7/Ang II, endothelial microparticles, platelet microparticles, von Willebrand/ADAMTS13). In order to assess the prediction of MACE (cardiac death, re-infarction, stroke) at 1-st year, the relative risk of markers that had significant differences in patients with MACE versus without MACE in both groups (STEMI and NSTEMI) was assessed. The control group consisted of 40 apparently healthy people. Results. The MACE rate in STEMI and NSTEMI patients at 1 year was similar, 29% and 28%, respectively. All markers of endothelial dysfunction explored had significant deviations from control. Of these, however, only 4 markers had significant different values in patients (STEMI and NSTEMI) with MACE vs without MACE: neopterin, endocan, L-Arginine/ADMA and Ang 1-7/Ang II. Remarkably, all 3 markers of hemostasis explored had circulating levels in patients who developed MACE significantly higher than patients without MACE, which significantly exceeded the control marker. The assessment of the relative risk value has allowed the delineation of markers regarding the prediction of MACE such as: von Willebrand/ADAMTS13, platelet microparticles, fibrin monomers, endocan, neopterin, Ang 1-7/ Ang II, L-Arginine/ADAMTS13. Conclusions. 1. Endothelial dysfunction and compromised hemostasis are pathophysiological pillars of CMD which influences the MACE risk, and thus new markers such as von Willebrand/ADAMTS13 ratio, platelet microparticles, endocan, the ratio Ang 1-7/Ang II and L/Arginine/ ADMAs have notable predictive value on MACE.2. Since CMD may be a key mechanism of cardiac ischemia in chronic non-obstructive coronary artery disease (<50%) its evaluation, including through the identified predictors, has a conclusive diagnostic and prognostic relevance.

Acute strength exercise training impacts differently the HERV-W expression and inflammatory biomarkers in resistance exercise training individuals.

Human Endogenous Retroviruses (HERVs) are fossil viruses that composes 8% of the human genome and plays several important roles in human physiology, including muscle repair/myogenesis. It is believed that inflammation may also regulate HERV expression, and therefore may contribute in the muscle repair, especially after training exercise. Hence, this study aimed to assess the level of HERVs expression and inflammation profile in practitioners' resistance exercises after an acute strength training session. Healthy volunteers were separated in regular practitioners of resistance exercise training group (REG, n = 27) and non-trained individuals (Control Group, n = 20). All individuals performed a strength exercise section. Blood samples were collected before the exercise (T0) and 45 minutes after the training session (T1). HERV-K (HML1-10) and W were relatively quantified, cytokine concentration and circulating microparticles were assessed. REG presented higher level of HERV-W expression (~2.5 fold change) than CG at T1 (p<0.01). No difference was observed in the levels of HERV-K expression between the groups as well as the time points. Higher serum TNF-α and IL-10 levels were verified post-training session in REG and CG (p<0.01), and in REG was found a positive correlation between the levels of TNF-α at T1 and IL-10 at T0 (p = 0.01). Finally, a lower endothelial microparticle percentage was observed in REG at T1 than in T0 (p = 0.04). REG individuals exhibited a significant upregulation of HERV-W and modulation of inflammatory markers when compared to CG. This combined effect could potentially support the process of skeletal muscle repair in the exercised individuals.

Translational Research of the Acute Effects of Negative Emotions on Vascular Endothelial Health: Findings From a Randomized Controlled Study.

Provoked anger is associated with an increased risk of cardiovascular disease events. The underlying mechanism linking provoked anger as well as other core negative emotions including anxiety and sadness to cardiovascular disease remain unknown. The study objective was to examine the acute effects of provoked anger, and secondarily, anxiety and sadness on endothelial cell health. Apparently healthy adult participants (n=280) were randomized to an 8-minute anger recall task, a depressed mood recall task, an anxiety recall task, or an emotionally neutral condition. Pre-/post-assessments of endothelial health including endothelium-dependent vasodilation (reactive hyperemia index), circulating endothelial cell-derived microparticles (CD62E+, CD31+/CD42-, and CD31+/Annexin V+) and circulating bone marrow-derived endothelial progenitor cells (CD34+/CD133+/kinase insert domain receptor+ endothelial progenitor cells and CD34+/kinase insert domain receptor+ endothelial progenitor cells) were measured. There was a group×time interaction for the anger versus neutral condition on the change in reactive hyperemia index score from baseline to 40 minutes (P=0.007) with a mean±SD change in reactive hyperemia index score of 0.20±0.67 and 0.50±0.60 in the anger and neutral conditions, respectively. For the change in reactive hyperemia index score, the anxiety versus neutral condition group by time interaction approached but did not reach statistical significance (P=0.054), and the sadness versus neutral condition group by time interaction was not statistically significant (P=0.160). There were no consistent statistically significant group×time interactions for the anger, anxiety, and sadness versus neutral condition on endothelial cell-derived microparticles and endothelial progenitor cells from baseline to 40 minutes. In this randomized controlled experimental study, a brief provocation of anger adversely affected endothelial cell health by impairing endothelium-dependent vasodilation.

Clinical and Serological Associations of Subclinical Atherosclerosis in Spondyloarthropathy

Background: Patients with spondyloarthropathy (SpA) have a higher risk of subclinical atherosclerosis (SCA). We assessed clinical and serological determinants of SCA in Indian SpA patients. Methods: Patients with SpA (fulfilling ASAS 2010 criteria; n = 104) attending our hospital were recruited; mean carotid intima-media thickness (CIMT) was performed by carotid ultrasonography, along with clinical assessment and traditional risk factor evaluation. Microparticles were extracted from plasma and total, as well as endothelial microparticles (EMP), platelet microparticles, T lymphocyte microparticles and B lymphocyte microparticles, were analysed by flow cytometry. Serum samples were analysed for inflammatory cytokines previously implicated in atherosclerosis, namely interleukin 1β (IL-1β), IL-6, IL-17, IL-27, IL-33 and tumour necrosis factor-alpha. Thirty-eight healthy controls were used for comparison. Subgroup analyses compared parameters between SpA with SCA (i.e., with carotid plaque or more than 75th percentile of CIMT for that age and sex in the Indian population) versus those without SCA. Ethical approval and written, informed consent were obtained. Results: Despite significantly younger age, lower body mass index and higher total cholesterol in controls compared to SpA, those with SpA had higher CIMT. Traditional cardiovascular risk factors (older age, higher waist-hip ratio) and novel markers of inflammation (serum IL-1β, IL-6) were associated with SCA. While total microparticles, EMP, T lymphocyte and B lymphocyte microparticles were increased in SpA than in healthy controls, they were not associated with SCA. Conclusions: Traditional risk factors and serum inflammatory cytokines IL-1β and IL-6 are associated with higher SCA in Indian SpA patients.

Clinical and Serological Associations of Subclinical Atherosclerosis in Systemic Sclerosis

Background: While patients with systemic sclerosis (SSc) are predisposed to cardiovascular events, data regarding this from India is sparse. We analysed correlates of subclinical atherosclerosis in Indian patients with SSc. Methods: Patients with SSc fulfilling the 2013 classification criteria ( n = 61) were recruited after obtaining written informed consent. Clinical risk factors for cardiovascular disease (CVD) were assessed. A carotid ultrasound was performed to assess the mean carotid intima-media thickness (CIMT). Total and endothelial microparticles (EMP, positive for CD31 and CD146) were estimated from plasma. Serum cytokines known to play a role in atherosclerosis (interleukin-1β [IL-1β], tumour necrosis factor-alpha, IL-6 and IL-17) were assessed. Forty-one age- and sex-similar healthy controls were recruited for comparison. Clinical and serological risk factors for CVD were compared between SSc with and without carotid plaque. Linear regression analyses were conducted to identify predictors of CIMT and carotid plaque in SSc. Results: Patients with SSc had lower body-mass index than healthy controls, however, had higher CIMT, higher serum IL-1β, IL-6, total microparticles and EMP than control subjects. SSc with carotid plaque ( n = 13) were older, and more likely to be male, but demonstrated no differences in serological markers of CVD. On multivariable-adjusted regression analyses, age was the only significant predictor of CIMT in SSc and male sex was the only significant predictor of carotid plaque in SSc. Conclusions: Carotid plaques were present in one-fifth of young patients with SSc. Older age and male sex predicted a higher risk of subclinical atherosclerosis in SSc.

Biochanin A inhibits endothelial dysfunction induced by IL‑6‑stimulated endothelial microparticles in Perthes disease via the NFκB pathway.

Endothelial dysfunction caused by the stimulation of endothelial microparticles (EMPs) by the inflammatory factor IL-6 is one of the pathogenic pathways associated with Perthes disease. The natural active product biochanin A (BCA) has an anti-inflammatory effect; however, whether it can alleviate endothelial dysfunction in Perthes disease is not known. The present in vitro experiments on human umbilical vein endothelial cells showed that 0-100 pg/ml IL-6-EMPs could induce endothelial dysfunction in a concentration-dependent manner, and the results of the Cell Counting Kit 8 assay revealed that, at concentrations of <20 µM, BCA had no cytotoxic effect. Reverse transcription-quantitative PCR demonstrated that BCA reduced the expression levels of the endothelial dysfunction indexes E-selectin and intercellular cell adhesion molecule-1 (ICAM-1) in a concentration-dependent manner. Immunofluorescence and western blotting illustrated that BCA increased the expression levels of zonula occludens-1 and decreased those of ICAM-1. Mechanistic studies showed that BCA inhibited activation of the NFκB pathway. In vivo experiments demonstrated that IL-6 was significantly increased in the rat model of ischemic necrosis of the femoral head, whereas BCA inhibited IL-6 production. Therefore, in Perthes disease, BCA may inhibit the NFκB pathway to suppress IL-6-EMP-induced endothelial dysfunction, and could thus be regarded as a potential treatment for Perthes disease.

Reviewing migraine-associated pathophysiology and its impact on elevated stroke risk.

Migraine affects up to 20 percent of the global population and ranks as the second leading cause of disability worldwide. In parallel, ischemic stroke stands as the second leading cause of mortality and the third leading cause of disability worldwide. This review aims to elucidate the intricate relationship between migraine and stroke, highlighting the role of genetic, vascular, and hormonal factors. Epidemiological evidence shows a positive association between migraine, particularly with aura, and ischemic stroke (IS), though the link to hemorrhagic stroke (HS) remains inconclusive. The shared pathophysiology between migraine and stroke includes cortical spreading depression, endothelial dysfunction, and genetic predispositions, such as mutations linked to conditions like CADASIL and MELAS. Genetic studies indicate that common loci may predispose individuals to both migraine and stroke, while biomarkers such as endothelial microparticles and inflammatory cytokines offer insights into the underlying mechanisms. Additionally, hormonal influences, particularly fluctuations in estrogen levels, significantly impact migraine pathogenesis and stroke risk, highlighting the need for tailored interventions for women. The presence of a patent foramen ovale (PFO) in migraineurs further complicates their risk profile, with device closure showing promise in reducing stroke occurrence. Furthermore, white matter lesions (WMLs) are frequently observed in migraine patients, suggesting potential cognitive and stroke risks. This review hopes to summarize the links between migraine and its associated conditions and ischemic stroke, recognizing the profound implications for clinical management strategies for both disorders. Understanding the complex relationship between migraine and ischemic stroke holds the key to navigating treatment options and preventive interventions to enhance overall patient outcomes.

Endothelial Microparticles: Markers of Inflammatory Response After Sutureless Valve Implantation.

Systemic inflammatory response syndrome (SIRS) is related to increased circulating endothelial microparticles (EMP). The aim of this study was to compare the plasma concentration of EMP between patients undergoing aortic valve replacement with conventional bioprosthesis implantation and Perceval™ S (LivaNova) and to evaluate its impact on the inflammatory response in the short-term follow-up. This is a randomized clinical trial with 24 patients submitted to isolated aortic valve replacement divided into two groups: Perceval™ S (Group P) and conventional bioprostheses (Group C). Incidence of severe SIRS (three or more criteria) in the first 48 hours postoperatively, EMP release profile, interleukins (IL) 6 and 8, C-reactive protein, and procalcitonin were analyzed preand postoperatively at 24 hours and three months. There were 24 patients (12 in each group), mean age was 69.92±5.17 years, 83.33% were female, the incidence of severe SIRS was 66.7% and 50% in groups C and P, respectively (P=0.68), and EMP showed a significant increase in the 24-hour postoperative period (P≤0.001) and subsequent decrease in the three-month postoperative period (P≤0.001), returning to baseline levels. For IL-6 and IL-8, there was a greater increase in group C at 24 hours postoperatively (P=.0.02 and P<0.001). The incidence of severe SIRS was similar in both groups, with significantly higher levels of IL-6 and IL-8, at the 24-hour postoperative period, in group C, however with higher levels of EMP in group P, and subsequent return to baseline levels at the three-month postoperative period in both groups.

Early Human Pathophysiological Responses to Exertional Hypobaric Decompression Stress.

INTRODUCTION: Consistent blood biomarkers of hypobaric (altitude) decompression stress remain elusive. Recent laboratory investigation of decompression sickness risk at 25,000 ft (7620 m) enabled evaluation of early pathophysiological responses to exertional decompression stress.METHODS: In this study, 15 healthy men, aged 20-50 yr, undertook 2 consecutive (same-day) ascents to 25,000 ft (7620 m) for 60 and 90 min, breathing 100% oxygen, each following 1 h of prior denitrogenation. Venous blood was sampled at baseline (T0), immediately after the second ascent (T8), and next morning (T24). Analyses encompassed whole blood hematology, endothelial microparticles, and soluble markers of cytokine response, endothelial function, inflammation, coagulopathy, oxidative stress, and brain insult, plus cortisol and creatine kinase.RESULTS: Acute hematological effects on neutrophils (mean 72% increase), eosinophils (40% decrease), monocytes (37% increase), and platelets (7% increase) normalized by T24. Consistent elevation (mean five-fold) of the cytokine interleukin-6 (IL-6) at T8 was proinflammatory and associated with venous gas emboli (microbubble) load. Levels of C-reactive protein and complement peptide C5a were persistently elevated at T24, the former by 100% over baseline. Additionally, glial fibrillary acidic protein, a sensitive marker of traumatic brain injury, increased by a mean 10% at T24.CONCLUSIONS: This complex composite environmental stress, comprising the triad of hyperoxia, decompression, and moderate exertion at altitude, provoked pathophysiological changes consistent with an IL-6 cytokine-mediated inflammatory response. Multiple persistent biomarker disturbances at T24 imply incomplete recovery the day after exposure. The elevation of glial fibrillary acidic protein similarly implies incomplete resolution following recent neurological insult.Connolly DM, Madden LA, Edwards VC, D'Oyly TJ, Harridge SDR, Smith TG, Lee VM. Early human pathophysiological responses to exertional hypobaric decompression stress. Aerosp Med Hum Perform. 2023; 94(10):738-749.

Initiation of combined antiretroviral therapy confers suboptimal beneficial effects on neurovascular function in people with HIV.

Due to advances in combined anti-retroviral treatment (cART), there is an increased burden of age-related cerebrovascular disease (CBVD), in people living with HIV (PWH). The underlying CNS injury can be assessed by measuring cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). 35 treatment-naïve PWH and 53 HIV negative controls (HC) were enrolled in this study. Study participants underwent T1-weighted anatomical, pseudo-continuous arterial spin labeling, and resting-state functional MRI to obtain measures of CBF and CVR prior to starting cART treatment and at two-time points (12 weeks and 2 years) post-cART initiation. Controls were scanned at the baseline and 2-year visits. We also measured plasma levels of microparticles of endothelial and glial origin and well-known endothelial inflammation markers, ICAM-1 and VCAM-1, to assess HIV-associated endothelial inflammation and the interaction of these peripheral markers with brain neurovascular function. HIV infection was found to be associated with reduced CVR and increased levels of endothelial and glial microparticles (MPs) prior to initiation of cART. Further, CVR correlated negatively with peripheral MP levels in PWH. Our results suggest that while cART treatment has a beneficial effect on the neurovascular function after initiation, these benefits are suboptimal over time.

Microparticles: potential new contributors to the pathogenesis of systemic sclerosis?

BackgroundMicroparticles (MPs) are membrane-derived vesicles released from cells undergoing activation or apoptosis with diverse proinflammatory and prothrombotic activities, that have been implicated in the pathogenesis of systemic sclerosis (SSc). We aimed to evaluate the plasma levels of platelet-derived microparticles (PMPs), endothelial cell-derived microparticles (EMPs), and monocyte-derived microparticles (MMPs) in SSc patients, and the association between MPs and the clinical features of SSc.MethodsIn this cross-sectional study, 70 patients with SSc and 35 age- and sex-matched healthy controls were evaluated. Clinical and nailfold capillaroscopy (NFC) data were obtained from all patients. Plasma levels of PMPs (CD42+/31+), EMPs (CD105+), and MMPs (CD14+) were quantified by flow cytometry.ResultsPatients were mainly females (90%), with a mean age of 48.9 years old. PMP, EMP, and MMP levels were significantly increased in SSc patients compared to controls (79.2% ± 17.3% vs. 71.0% ± 19.8%, p = 0.033; 43.5% ± 8.7% vs. 37.8% ± 10.4%, p = 0.004; and 3.5% ± 1.3% vs. 1.1% ± 0.5%, p < 0.0001, respectively). PMP levels were significantly higher in patients with positive anti-topoisomerase-I antibodies (p = 0.030) and in patients with a disease duration > 3 years (p = 0.038). EMP levels were lower in patients with a higher modified Rodnan skin score (p = 0.015), and in those with an avascular score > 1.5 in NFC (p = 0.042).ConclusionThe increased levels of PMPs, EMPs and MMPs in scleroderma patients might indicate a possible role for these agents in the pathogenesis of this challenging disease.