Thrombosis Formation Research Articles

Polyamino Acid Based Zwitterionic Coating can Inhibit Coagulation and Inflammation Through Anti-Fouling and Restoring Microenvironment.

Protein adhesion and thrombosis formation caused by limited surface properties pose great challenges to biomedical implants. Although various hydrophilic coating or drug release coatings are reported, the single coating cannot cope with cases under the condition of complex physiological environment, which causes the coating effect is limited. In this study, a polyamino acid-derived zwitterionic coating is constructed to eliminate reactive oxygen species (ROS) in the microenvironment. It is demonstrated that the coating has excellent hydrophilicity, stability, and lubricity, and can obviously prevent protein adhesion. At the same time, the coating can eliminate hydrogen peroxide and maintain the stability of the microenvironment. The in vivo and in vitro experiments show that the coating has good biocompatibility, and inhibits thrombus. Amino acid zwitterion coating prevents protein deposition, alleviates the inflammatory process, inhibit of thrombosis, reduces the risk of implantable medical devices, and prolongs their service time. Hence, the work paves a new way to develop amino acid based zwitterionic polymer coating that can reduce the implant complications.

Bow–Hunter Syndrome Due to Tandem Lesions; A Case Report

AbstractBow–Hunter syndrome (BHS) includes a form of stroke caused by dynamic factors affecting the extracranial vertebral artery (VA), such as rotation-induced flow disturbance at the atlantoaxial level. BHS is a rare condition that can result from a variety of factors, including abnormal bone compression and vertebral instability. So far, there have been no reports in which both vertebral instability and osteophytes compress the VA at different sites, leading to stroke. Herein, we present a rare case of stroke attributed to BHS involving thrombosis formation due to osteophyte compression at C3/4 and VA occlusion due to vertebral instability at the C4/5 overlapped. A 72-year-old male presented with rotational vertigo and vomiting associated with a cerebellar infarction. Digital subtraction angiography revealed severe stenosis of the left VA with an intra-arterial thrombus. Percutaneous transluminal angioplasty improved the stenosis; however, intravascular ultrasound revealed compression of the VA by osteophytes at C3/4. Additionally, left VA occlusion at C4/5 was confirmed because of vertebral instability. The osteophyte was removed via the anterolateral approach, and the VA was decompressed. The patient's postoperative course was uneventful, with no recurrence for more than 2 years. BHS can occur in the lower cervical spine when vertebral instability coincides with intimal arterial damage caused by osteophytes at other sites.

Mechanical Viability and Functionality Assessment of a New Sutureless Endoluminal Microvascular Device: A Preliminary In Vivo Rabbit Study.

Our group has developed a new nitinol endoluminal self-expandable device for microvascular anastomosis. It attaches to each vessel ending with opposite directed microspikes and reaches complete expansion at body temperature, using the nitinol shape memory capacity. The main purpose of this first in vivo trial is to evaluate the mechanical viability of the device and its immediate and early functionality. A recuperation study with seven New Zealand White rabbits was designed. A 1.96 mm outer diameter prototype of the new device was placed on the right femoral artery of each rabbit. Each anastomosis was reassessed on the seventh postoperative day to reevaluate the device function. The average anastomosis time with the new device was 18 min and 45 seg (±0.3 seg). It could be easily placed in all the cases with an average of 1.14 (1) complementary stitches needed to achieve a sealed anastomosis. Patency test was positive for all the cases on the immediate assessment. On the 1 week revision surgery, patency test was negative for the seven rabbits due to blood clot formation inside the device. The new device that we have developed is simple to use and shows correct immediate functionality. On the early assessment, the presence of a foreign body in the endoluminal space caused blood clot formation. We speculate that a heparin eluting version of the device could avoid thrombosis formation. We consider that the results obtained can be valuable for other endoluminal sutureless devices.

Counteraction of unconjugated bilirubin against heme-induced toxicity in platelets

Platelets are essential for normal hemostasis and thrombosis but become hyperactive in hemolytic disorders. Cell-free heme is known to be toxic to platelets and endothelial cells, playing a significant role in the progression of pathological complications in various hemolytic conditions. The abnormal activation of circulatory platelets results in micro/macrovascular thrombosis and clot formation in the lungs, worsening the disease. This work aimed to establish the potent bioactive molecule that can regulate the hemin-induced toxicity in platelets. We found that unconjugated bilirubin (UCB), an endogenous antioxidant and a byproduct of heme degradation, exhibited a higher protective effect against hemin-induced platelet aggregation and activation. This protective effect could mainly be due to reducing ROS and lipid peroxidation-mediated ferroptosis in hemin-treated platelets. Further experiments suggested that by blocking the interaction between hemin and the CLEC-2 receptor, UCB regulates the downstream Syk phosphorylation, a key event in hemin-induced platelet toxicity. Thus, UCB is emerging as a natural regulatory molecule that mitigates hemin-induced platelet toxicity and holds promise as an adjunctive therapy for managing platelet-associated complications, particularly in hemolytic disorders.

Absence of platelet overactivation and thrombosis formation among patients with coronary atherosclerosis disease after vaccination against SARS-CoV-2

BackgroundAssociation of Coronavirus disease 2019 vaccines with thrombosis has raised concerns among patients with coronary atherosclerosis disease (CAD). ObjectivesAfter vaccination against SARS-CoV-2, to detect thrombosis formation in atherosclerosis ApoE−/− mice, and platelet activation, coagulation, the profile of prothrombotic antibodies, and the production of platelet factor 4 (PF4) antibodies in patients with CAD. MethodsAtherosclerotic ApoE−/− mice were immunized with saline or inactivated SARS-CoV vaccines. We investigated FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo. Inpatients undergoing percutaneous coronary intervention (PCI) were consecutively enrolled and defined according to vaccination status. We evaluated coagulation by thrombelastograph (TEG), platelet activation makers by flow cytometry, PF4 antibody and antiphospholipid antibodies by ELISA, and SARS-CoV-2 neutralizing antibody. ResultsIn atherosclerotic ApoE−/− mice, FeCl3-induced thrombus formation and thrombus formation under flow conditions were similar between saline-treated and inactivated SARS-CoV-2 vaccines-treated groups. A total of 182 patients undergoing PCI were included in the final analysis, of whom 92 had been vaccinated. Baseline characteristics were well balanced between unvaccinated and vaccinated groups. The expression of PAC-1 and P-selectin, the prevalence of positivity for PF4 antibodies and antiphospholipid antibodies were similar between these two groups. ConclusionsInactivated SARS-CoV-2 vaccines did not potentiate thrombosis formation in atherosclerotic mice. Inactivated SARS-CoV-2 vaccines did not enhance platelet activation, or trigger the production of PF4 and antiphospholipid antibodies in patients with CAD. In light of the observed thrombotic risks associated with adenovirus-based COVID-19 vaccines, inactivated vaccines may offer a potentially safer option for individuals with CAD.

Parvovirus B19 Infection Is Associated with the Formation of Neutrophil Extracellular Traps and Thrombosis: A Possible Linkage of the VP1 Unique Region.

Neutrophil extracellular traps (NETs) formation, namely NETosis, is implicated in antiphospholipid syndrome (APS)-related thrombosis in various autoimmune disorders such as systemic lupus erythematosus (SLE) and APS. Human parvovirus B19 (B19V) infection is closely associated with SLE and APS and causes various clinical manifestations such as blood disorders, joint pain, fever, pregnancy complications, and thrombosis. Additionally, B19V may trigger the production of autoantibodies, including those against nuclear and phospholipid components. Thus, exploring the connection between B19V, NETosis, and thrombosis is highly relevant. An in vitro NETosis model using differentiated HL-60 neutrophil-like cells (dHL-60) was employed to investigate the effect of B19V-VP1u IgG on NETs formation. A venous stenosis mouse model was used to test how B19V-VP1u IgG-mediated NETs affect thrombosis in vivo. The NETosis was observed in the dHL-60 cells treated with rabbit anti-B19V-VP1u IgG and was inhibited in the presence of either 8-Br-cAMP or CGS216800 but not GSK484. Significantly elevated reactive oxygen species (ROS), myeloperoxidase (MPO), and citrullinated histone (Cit-H3) levels were detected in the dHL60 treated with phorbol myristate acetate (PMA), human aPLs IgG and rabbit anti-B19V-VP1u IgG, respectively. Accordingly, a significantly larger thrombus was observed in a venous stenosis-induced thrombosis mouse model treated with PMA, human aPLs IgG, rabbit anti-B19V-VP1u IgG, and human anti-B19V-VP1u IgG, respectively, along with significantly increased amounts of Cit-H3-, MPO- and CRAMP-positive infiltrated neutrophils in the thrombin sections. This research highlights that anti-B19V-VP1u antibodies may enhance the formation of NETosis and thrombosis and implies that managing and treating B19V infection could lower the risk of thrombosis.

Long-Term Hemorrhage and Reperfusion Rates of Coiled Aneurysms: A Single-Center Experience.

Background: The endovascular approach has emerged as standard therapy for many intracranial aneurysms (IAs) to prevent hemorrhage, yet its long-term durability varies considerably. The aim of this study was to evaluate the safety and effectiveness of an initially deliberate endovascular approach regarding IA hemorrhage rates over a long-term follow-up period. Methods: This retrospective single-center study included all consecutive patients with endovascularly treated IAs who presented between January 2008 and December 2020 with a follow-up of at least 12 months. The primary endpoint was the proportion of patients with long-term IA hemorrhage rates and reperfusion. The secondary endpoint was treatment-related morbidity and mortality. Independent risk factors for IA reperfusion over the long term were analyzed using multivariate logistic regression. Results: Endovascular treatment was the therapy of choice for 333 patients with IAs, among whom 188 (57%) experienced rupture upon presentation. Complete coiling (Raymond I) was noted in 162 (49%) of the patients, with primary supportive devices being used in 51 (15%) patients. After a median (±SD) follow-up time of 34 ± 41 months (range 12-265 months), IA reperfusion was noted in 158 (47%), necessitating retreatment in 105 (32%) of the patients. Over the long term, hemorrhage was noted in four (1%) patients. Multivariate analysis revealed aneurysmal multilobarity (HR 1.8, 95%CI 1.2-2.7; p = 0.004) and a patient age of ≥50 years (HR 1.7, 95% CI 1.1-2.5, p = 0.01) as independent predictors of reperfusion over time. Intervention-related morbidity was noted in 16 (4.8%) patients, namely, thrombosis formation and contrast extravasation in 8 (2.4%) patients each, while no intervention-induced mortality was observed. Conclusion: In the long term, the hemorrhage rate in patients with IA with an initially more conservative endovascular approach is low. Therefore, a deliberate endovascular treatment approach might be justified.

Construction and verification of a machine learning-based prediction model of deep vein thrombosis formation after spinal surgery

BackgroundDeep vein thromboembolism (DVT) is a common postoperative complication with high morbidity and mortality rates. However, the safety and effectiveness of using prophylactic anticoagulants for preventing DVT after spinal surgery remain controversial. Hence, it is crucial to predict whether DVT occurs in advance following spinal surgery. The present study aimed to establish a machine learning (ML)-based prediction model of DVT formation following spinal surgery. MethodsWe reviewed the medical records of patients who underwent elective spinal surgery at the Third Affiliated Hospital of Zunyi Medical University (TAHZMU) from January 2020 to December 2022. We ultimately selected the clinical data of 500 patients who met the criteria for elective spinal surgery. The Boruta-SHAP algorithm was used for feature selection, and the SMOTE algorithm was used for data balance. The related risk factors for DVT after spinal surgery were screened and analyzed. Five ML algorithm models were established. The data of 150 patients treated at the Affiliated Hospital of Zunyi Medical University (AHZMU) from July 2023 to October 2023 were used for external verification of the model. The area under the curve (AUC), geometric mean (G-mean), sensitivity, accuracy, specificity, and F1 score were used to evaluate the performance of the models. ResultsThe results revealed that activated partial thromboplastin time (APTT), age, body mass index (BMI), preoperative serum creatinine (Crea), anesthesia time, rocuronium dose, and propofol dose were the seven important characteristic variables for predicting DVT after spinal surgery. Among the five ML models established in this study, the random forest classifier (RF) showed superior performance to the other models in the internal validation set. ConclusionSeven preoperative and intraoperative variables were included in our study to develop an ML-based predictive model for DVT formation following spinal surgery, and this model can be used to assist in clinical evaluation and decision-making.

ShSPI Inhibits Thrombosis Formation and Ischemic Stroke In Vivo.

Thrombotic diseases, emerging as a global public health hazard with high mortality and disability rates, pose a significant threat to human health and longevity. Although current antithrombotic therapies are effective in treating these conditions, they often carry a substantial risk of bleeding, highlighting the urgent need for safer therapeutic alternatives. Recent evidence has increasingly pointed to a connection between elastase activity and thrombosis. In the current study, we investigated the antithrombotic effects of ShSPI, an elastase inhibitor peptide derived from the venom of Scolopendra hainanum. Results showed that ShSPI significantly attenuated carrageenan-induced thrombosis in vivo. Furthermore, ShSPI effectively inhibited the carrageenan-induced decrease in serum superoxide dismutase (SOD) activity and increase in prothrombin time, fibrinogen level, and endothelial nitric oxide synthase (eNOS) activity. In addition, ShSPI reduced intracerebral thrombosis and improved functional outcomes following ischemic stroke in a transient middle cerebral artery occlusion (tMCAO) mouse model. Collectively, these findings suggest that ShSPI is a promising candidate for the development of novel thrombotic therapies.

Polyphenol-Reinforced Glycocalyx-Like Hydrogel Coating Induced Myocardial Regeneration and Immunomodulation.

Although minimally invasive interventional occluders can effectively seal heart defect tissue, they still have some limitations, including poor endothelial healing, intense inflammatory response, and thrombosis formation. Herein, a polyphenol-reinforced medicine/peptide glycocalyx-like coating was prepared on cardiac occluders. A coating consisting of carboxylated chitosan, epigallocatechin-3-gallate (EGCG), tanshinone IIA sulfonic sodium (TSS), and hyaluronic acid grafted with 3-aminophenylboronic acid was prepared. Subsequently, the mercaptopropionic acid-GGGGG-Arg-Glu-Asp-Val peptide was grafted by the thiol-ene "click" reaction. The coating showed good hydrophilicity and free radical-scavenging ability and could release EGCG-TSS. The results of biological experiments suggested that the coating could reduce thrombosis by promoting endothelialization, and promote myocardial repair by regulating the inflammatory response. The functions of regulating cardiomyocyte apoptosis and metabolism were confirmed, and the inflammatory regulatory functions of the coating were mainly dependent on the NF-kappa B and TNF signaling pathway.

Anchor versus parachute suturing technique in arteriovenous fistula creation for hemodialysis.

Chronic kidney disease (CKD) affects 13% of the global population and requires renal replacement therapy due to ESRD. Hemodialysis (HD) is the most common dialysis modality for ESRD patients, but establishing vascular access is challenging due to high morbidity and mortality rates. Arteriovenous fistulas (AVFs) are the gold standard for vascular access, but many fail due to anastomotic hemodynamics, vein diameter, and anastomatic suture technique. A prospective study was conducted to evaluate the impact of two continuous suturing techniques, the anchor technique and the parachute technique, on AVFs' initial outcomes. This randomized, controlled study involved adult patients who presented for AVF creation at our center. We divided the patients into two groups: anchors and parachutes. Four skilled vascular access surgeons performed the procedures. The primary goal was functional maturation of the AVF, defined as an AVF fistula ready to be cannulated with a cannulating vein length of at least 10cm, a diameter of more than 6mm, a depth of less than 6mm, and a flow rate of 600mL/min. Secondary goals included patency and complications such as bleeding, infection, steal syndrome, and aneurysmal dilatation at the anastomosis site. AVFs were evaluated immediately after surgery and during follow-up visits at the outpatient clinic. A duplex scan was performed to measure flow at various intervals. All patients provided appropriate written consent. The study involved 186 patients, with 86 excluded. 100 were randomized, with 5 cases losing follow-up and 3 deaths within 12months. The follow-up continued until January 2024, with a mean of 8.6months. The Parachute technique shows higher technical success (p value = 0.046) and primary patency at 30days (p value = 0.014) compared to Anchor, but there is no statistical significance between both groups regarding functional maturation at 6 weeks (p value = 0.352). The parachute technique has a higher hematoma rate than the anchor technique (p value = 0.025), while other complications like intra-operative bleeding, postoperative bleeding, pseudoaneurysm formation, thrombosis, steal syndrome, and seroma formation show no significant differences. Nine patients, five of whom were diabetic and underwent conservative management, exhibited mild to moderate steal syndrome. This suggests an increased risk of steal syndrome among diabetic patients. The parachute technique for AVF creation offers better technical success and short-term primary patency outcomes, while both parachute and anchor techniques are equally effective for long-term functional maturation and overall complication rates.

Intravenous injection of nattokinase-heparin electrostatic complex improves the therapeutic effect of advanced tumors by dissolving cancer-related thrombosis

AimsCancer-related thrombosis (CAT) is a common complication in cancer patients, significantly impacting their quality of life and survival prospects. Nattokinase (NK) has potent thrombolytic properties, however, its efficacy is limited by low oral bioavailability and the risk of severe allergic reactions with intravenous use. Heparin (HP) is a widely used anticoagulant in clinical settings. This study aimed to overcome the intravenous toxicity of NK and explore its effect on CAT in advanced tumors. Main methodsIn this study, NK-HP electrostatic complexes were constructed, and their safety and thrombolytic efficacy were verified through guinea pig allergy tests, mouse tail vein tests, and both in vivo and in vitro thrombolysis experiments. Additionally, an S180 advanced tumor model was developed and combined with sialic acid-modified doxorubicin liposomes (DOX-SAL) to investigate the impact of NK-HP on CAT and its antitumor effects in advanced tumors. Key findingsWe observed that NK-HP can eliminate the intravenous injection toxicity of NK, has strong thrombolytic performance, and can prevent thrombosis formation. Intravenous injection of NK-HP can enhance the antitumor effect of DOX-SAL by reducing the fibrin content in advanced tumors and increasing the levels of the cross-linked protein degradation product D-dimer. SignificanceThis study developed a method to eliminate the intravenous injection toxicity of NK, proposing a promising therapeutic strategy for CAT treatment, particularly for CAT in advanced tumors, and improving the efficacy of nano-formulations in anti-tumor therapy.

Customized Vascular Repair Microenvironment: Poly(lactic acid)-Gelatin Nanofibrous Scaffold Decorated with bFGF and Ag@Fe3O4 Core-Shell Nanowires.

Vascular defects caused by trauma or vascular diseases can significantly impact normal blood circulation, resulting in serious health complications. Vascular grafts have evolved as a popular approach for vascular reconstruction with promising outcomes. However, four of the greatest challenges for successful application of small-diameter vascular grafts are (1) postoperative anti-infection, (2) preventing thrombosis formation, (3) utilizing the inflammatory response to the graft to induce tissue regeneration and repair, and (4) noninvasive monitoring of the scaffold and integration. The present study demonstrated a basic fibroblast growth factor (bFGF) and oleic acid dispersed Ag@Fe3O4 core-shell nanowires (OA-Ag@Fe3O4 CSNWs) codecorated poly(lactic acid) (PLA)/gelatin (Gel) multifunctional electrospun vascular grafts (bAPG). The Ag@Fe3O4 CSNWs have sustained Ag+ release and exceptional photothermal capabilities to effectively suppress bacterial infections both in vitro and in vivo, noninvasive magnetic resonance imaging (MRI) modality to monitor the position of the graft, and antiplatelet adhesion properties to promise long-term patency. The gradually released bFGF from the bAPG scaffold promotes the M2 macrophage polarization and enhances the recruitment of macrophages, endothelial cells (ECs) and fibroblast cells. This significant regulation of diverse cell behavior has been proven to be beneficial to vascular repair and regeneration both in vitro and in vivo. Therefore, this study supplies a method to prepare multifunctional vascular-repair materials and is expected to represent a significant guidance and reference to the development of biomaterials for vascular tissue engineering.

The emerging role of fibrin(ogen) in cardiovascular disease.

A coagulation factor called fibrinogen is produced by the liver and is proteolyzed by thrombin to become fibrin. The latest studies have revealed that fibrin(ogen) palys an essential role in the regulation of cardiovascular disease. Understanding the relationship and mechanism between fibrin(ogen) and cardiovascular disease is of great significance for maintaining overall health. The objective of this review is to discuss the specific involvement and underlying mechanisms of fibrin(ogen) in cardiovascular disease. A review was conducted using the PubMed database to identify and analyze the emerging role of fibrinogen in cardiovascular disease. The literature review revealed that fibrin(ogen) plays a pivotal role in maintaining cardiovascular disease and are involved in the pathogenesis of cardiovascular disease. Fibrin(ogen) mainly influence various pathophysiological processes, such as participating in thrombosis formation, stimulating the inflammatory response, and other molecular pathways. This review focuses on the involvement of fibrin(ogen) in cardiovascular disease, with a particular emphasis on the main functions and underlying mechanisms by which fibrin(ogen) influence the pathogenesis and progression of these conditions. This review underscores the potential of fibrin(ogen) as therapeutic targets in managing cardiovascular disease.

Selective Btk inhibition by PRN1008/PRN473 blocks human CLEC-2, and PRN473 reduces venous thrombosis formation in mice

AbstractPlatelet C-type lectin-like receptor 2 (CLEC-2) is a hem-immunoreceptor tyrosine–based activation motif-containing receptor that has a critical role in venous thrombosis but minimal involvement in hemostasis. CLEC-2 can be blocked by Btk inhibitors. Treatment with ibrutinib is associated with increased bleeding due to off-target inhibition of Src family kinases (SFKs). Patients with X-linked agammaglobulinemia (XLA) who lack Btk, however, do not bleed, suggesting selective Btk inhibition as a viable antithrombotic strategy. We assessed the effects of selective Btk inhibitors PRN1008 (rilzabrutinib) and PRN473 on platelet signaling and function mediated by CLEC-2 and glycoprotein-VI. We used healthy donors and XLA platelets to determine off-target inhibitor effects. Inferior vena cava (IVC) stenosis and Salmonella infection mouse models were used to assess antithrombotic effects of PRN473 in vivo. PRN1008 and PRN473 potently inhibited CLEC-2–mediated platelet activation to rhodocytin. No off-target inhibition of SFKs was seen. PRN1008 treatment of Btk-deficient platelets resulted in minor additional inhibition of aggregation and tyrosine phosphorylation, likely reflecting inhibition of Tec. No effect on G protein-coupled receptor-mediated platelet function was observed. PRN473 significantly reduced the number of thrombi in podoplanin-positive vessels after Salmonella infection and the presence of IVC thrombosis after vein stenosis. The potent inhibition of human platelet CLEC-2 and reduced thrombosis in in vivo models, together with the lack of off-target SFK inhibition and absence of bleeding reported in rilzabrutinib-treated patients with immune thrombocytopenia, suggest Btk inhibition as a promising antithrombotic strategy.

A comprehensive review on the association and prevention of long-term COVID-induced heart failure: A review.

The coronavirus disease 2019 (COVID-19) disease caused by the severe acute respiratory syndrome coronavirus 2 has had a widespread global impact. In addition to the main respiratory symptoms, research has found significant effects of this virus on the cardiovascular system. This article comprehensively explores the phenomenon of "long-term COVID-19" or postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection, wherein some recovered patients continue to experience long-term health issues after the resolution of acute illness. We delve into the potential reasons behind these symptoms, including increased risk of heart disease, myocardial injury, abnormal inflammatory responses, thrombosis formation, and immune system dysfunction, among others. Furthermore, this paper highlights the potential association between long-term COVID-19 and HF (heart failure), and proposes corresponding preventive strategies. To address this, we advocate for a collaborative approach involving interdisciplinary teams for treatment and management.

A Case of Arterial Thoracic Outlet Syndrome Thrombus Extending to Juxtavertebral Artery

Arterial thoracic outlet syndrome (TOS) constitutes less than 1%, involving the second part of the subclavian artery (SCA). It can present as an acute upper limb ischemia or aneurysm formation. Here is a case of a 29-year-old male presented with complaints of rest pain over the left hand for the past 2 weeks. Upon evalution, found to have bilateral cervical rib with left subclavian artery occlusion. Treated by cervical rib excision decompression of scalene triangle, subclavian endarterectomy and left brachial embolectomy. Arterial TOS secondary to the cervical rib is rare; pathology involving this external compression results in repeated trauma in the intima of the SCA, resulting in subclavian stenosis, poststenotic dilatation, thrombosis, and aneurysm formation with mural thrombus and distal embolization. Symptomatic cases need decompression +/- arterial repair.

Comparative Study of the Reactivity of Animal-Derived Blood on Medical Device Materials using Hematology and Platelet Activity Tests

In accordance with the requirements of ISO 10993-4, we established the feasibility of conditions for animal blood application in vitro to identify substances that induce thrombus formation and confirmed the differences in blood reactivity between animals necessary for interpreting in vivo results in this study. To this end, differences in the response of rabbit, pig, and monkey blood to each anticoagulant presented in ASTM F2888-19 were tested. It was confirmed that the direct heparinization method had a higher test sensitivity than that of recalcified sodium citrate, thus distinguishing thrombotic substances regardless of the test species. Particularly in pig blood, platelet and white blood cell counts showed the greatest decrease after reactions with various test materials. Expression of β-TG and PMN-elastase, indicators for platelet and leukocyte activities, was confirmed in pig blood when reacted with various test materials. A decrease in platelet count and significant increase in β-TG were observed in the black rubber test group, which was the positive candidate material. Conversely, a decreased leukocyte count was confirmed, but an increase in the expression of PMN-elastase was not observed. This result satisfied the ISO 10993-4 criteria for determining a positive thromboembolic substance. This study provided additional information on the selection of anticoagulants for the design of trials and selection of animal species for evaluating thrombosis formation on medical device materials by using the methods described in ISO 10993-4 and ASTM F2888-19.

Pharmacologic Inhibition of Ferroptosis Attenuates Experimental Abdominal Aortic Aneurysm Formation.

The pathogenesis of abdominal aortic aneurysm (AAA) formation involves vascular inflammation, thrombosis formation and programmed cell death leading to aortic remodeling. Recent studies have suggested that ferroptosis, an excessive iron-mediated cell death, can regulate cardiovascular diseases, including AAAs. However, the role of ferroptosis in immune cells, like macrophages, and ferroptosis-related genes in AAA formation remains to be deciphered. Single cell-RNA sequencing of human aortic tissue from AAA patients demonstrates significant differences in ferroptosis-related genes compared to control aortic tissue. Using two established murine models of AAA and aortic rupture in C57BL/6 (WT) mice, we observed that treatment with liproxstatin-1, a specific ferroptosis inhibitor, significantly attenuated aortic diameter, pro-inflammatory cytokine production, immune cell infiltration (neutrophils and macrophages), increased smooth muscle cell α-actin expression and elastic fiber disruption compared to mice treated with inactivated elastase in both pre-treatment and treatment after a small AAA had already formed. Lipidomic analysis using mass spectrometry shows a significant increase in ceramides and a decrease in intact lipid species levels in murine tissue compared to controls in the chronic AAA model on day 28. Mechanistically, in vitro studies demonstrate that liproxstatin-1 treatment of macrophages mitigated the crosstalk with aortic smooth muscle cells (SMCs) by downregulating MMP2 secretion. Taken together, this study demonstrates that pharmacological inhibition by liproxstatin-1 mitigates macrophage-dependent ferroptosis contributing to inhibition of aortic inflammation and remodeling during AAA formation.

Post-covid Syndrome in the Form of Venous and Arterial Thrombosis Complicated COVID-19

Post-covid syndrome in the form of thrombosis is a common and dangerous complication of COVID-19. To identify the localization, frequency, timing of thrombosis in patients who have undergone COVID-19, the frequency of surgical treatment methods used. A retrospective observational study of 239 case histories of patients (138 women and 101 men) who had COVID-19 in the Department of Vascular Surgery of the National Hospital of the Ministry of Health of the Kyrgyz Republic within the period from August to December 2020. A 42-year-old patient who underwent COVID-19 in March 2020, which gave a post-covid complication in the form of a chronic aneurysm of the infrarenal abdominal aorta five months later. Venous thrombosis as a post-covid syndrome is 74% more common than arterial thrombosis. The incidence of thrombotic post-covid syndrome in women compared to men is 15.4% higher. This trend is most pronounced in the disabled aged 61 and over. Venous thrombosis was most often localized in the veins of the lower extremities, and open surgical interventions were most often performed. People with concomitant diseases, in particular, with diseases of the cardiovascular system, are more susceptible to post-covid complications in the form of thrombosis and thromboembolism. Out of 239 people, 138 people (58%) had concomitant diseases, 101 people (42%) did not have them. Basically, open surgical interventions were performed. In 50% of cases with arterial thrombosis, thromboembolectomy was performed, with venous thrombi, the ligation of the great saphenous vein according to Troyanov accounted for 78% of operations. In the case of an individual clinical patient, laparotomy, nephrectomy on the right, elimination of an aortic aneurysm, aorto-femoral bifurcation prosthetics with an ECOFLONprosthesis were performed. Post-covid syndrome after COVID-19 is mainly localized in the veins of the lower extremities and is much more common among the female population with concomitant diseases. Open surgical operations can effectively eliminate the post-covid syndrome.