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Biomedicine & Pharmacotherapy =... Feb 2020Arterial thrombosis (AT) causes various ischemia-related diseases, which impose a serious medical burden worldwide. As an inhibitor of myosin II, blebbistatin has an...
Arterial thrombosis (AT) causes various ischemia-related diseases, which impose a serious medical burden worldwide. As an inhibitor of myosin II, blebbistatin has an important role in thrombosis development. We investigated the effect of blebbistatin on carotid artery ligation (CAL)-induced carotid AT and its potential underlying mechanism. A model of carotid AT in mice was generated by CAL. Mice were divided into three groups: CAL model, blebbistatin-treated, and sham-operation. After 7 days, blood vessels were harvested from mice in each group. The procoagulant activity of tissue factor (TF) was tested by a chromogenic assay, and thrombus severity assessed by histopathology scores. Expression of non-muscle myosin heavy chain II A (NMMHCIIA), TF, glycogen synthase kinase 3β (GSK3β), and nuclear factor-kappa B (NF-κB) was detected by immunohistochemical and immunofluorescence staining. mRNA expression was measured by quantitative polymerase chain reaction. Blebbistatin (1 mg/kg) inhibited development of carotid AT, reduced infiltration of inflammatory cells, and prevented vascular-tissue damage, relative to the model group. Furthermore, blebbistatin also reduced the procoagulant activity of TF. Immunohistochemical and immunofluorescence data demonstrated that, compared with the model group, blebbistatin intervention reduced expression of NMMHCIIA, TF, GSK3β, p65, and p-p65 in carotid-artery endothelia in the CAL-induced AT model, but it increased levels of p-GSK3β. Blebbistatin could inhibit expression of NMMHCIIA mRNA in the CAL model. Overall, our data demonstrated that blebbistatin could inhibit TF expression and AT development in arterial endothelia (at least in part) via GSK3β/NF-κB signaling.
Topics: Animals; Arteries; Cytoskeletal Proteins; Glycogen Synthase Kinase 3 beta; Heterocyclic Compounds, 4 or More Rings; Male; Mice; Mice, Inbred C57BL; Myosin Type II; NF-kappa B; Signal Transduction; Thrombosis
PubMed: 31918291
DOI: 10.1016/j.biopha.2019.109775 -
Transplant International : Official... Jan 2018Little is known about nonsurgical risk factors for hepatic artery thrombosis (HAT) after liver transplantation (LT). We determined risk factors for HAT occurring within...
Little is known about nonsurgical risk factors for hepatic artery thrombosis (HAT) after liver transplantation (LT). We determined risk factors for HAT occurring within 90 days post-LT and analysed the effect of HAT on graft and patient survival. Donor and recipient demographics, surgery-related data and outcome in transplants complicated by thrombosis (HAT+) and their matched controls (HAT-) were compared. Risk factors were assessed by univariate logistic regression. Median (IQR) is given. A total of 25 HAT occurred among 1035 adult LT (1/1997-12/2014) and 50 controls were manually matched. Donor and recipient demographics were similar. Pre-LT trans-catheter arterial chemo-embolization (TACE) was more frequent in HAT+ (HAT+ 20% vs. HAT- 4%, P = 0.037). HAT+ had longer implantation [HAT+ 88 min (76-108) vs. HAT- 77 min (66-93), P = 0.028] and surgery times [HAT+ 6.25 h (5.18-7.47) vs. HAT- 5.25 h (4.33-6.5), P = 0.001]. Early graft dysfunction and sepsis were more frequent in HAT+ and hospitalization longer. TACE had the greatest odds ratio in unadjusted analysis (OR: 6, 95% CI: 1.07-33.53, P = 0.03). All but seven grafts were lost after HAT (HAT+ 72% vs. HAT- 36%, P = 0.003); however, patient survival was unaffected (HAT+ 79.8% vs. HAT- 76%, P = 0.75). LT candidates undergoing TACE are at risk of developing HAT early after transplant.
Topics: Belgium; Chemoembolization, Therapeutic; Female; Graft Survival; Hepatic Artery; Humans; Liver Transplantation; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Risk Factors; Thrombosis
PubMed: 28869805
DOI: 10.1111/tri.13046 -
Medicine Apr 2023Low molecular weight heparins are widely used in various thrombotic diseases and exert a preventive effect on thrombosis in high-risk patients. Umbilical artery... (Review)
Review
RATIONALE
Low molecular weight heparins are widely used in various thrombotic diseases and exert a preventive effect on thrombosis in high-risk patients. Umbilical artery thrombosis (UAT) is a rare occurrence that is difficult to detect during routine prenatal visits but can lead to adverse perinatal outcomes.
PATIENT CONCERNS
The aim of this study was to elucidate the therapeutic effect of low molecular weight heparins on UAT and to provide a new treatment option for the timing of delivery timing.
DIAGNOSES AND INTERVENTIONS
A retrospective study was conducted on cases involving thrombosis of the umbilical cord enrolled from July 2017 to July 2022. Data were acquired and analyzed from medical records and the final diagnosis was confirmed by histopathology. All included patients received LWMHs therapy after initial diagnosis of UAT.
OUTCOMES
The mean age of the 10 pregnant women recruited into this study was 27.9 ± 4.0 year-of-age; 1 (10%) was elderly. The gestational age at diagnosis was 29.9 ± 3.7 weeks, the gestational age at termination was 36.3 ± 2.5 weeks and the mean gestational age of extension was 6.4 ± 4.2 weeks. Low molecular weight heparin sodium was administered after umbilical artery embolism was detected on ultrasound. The LWMHs treatment received by the included patients in this study was subcutaneous injection. The specific usage varies due to the types of LWMHs. Of the 10 cases, 5 (50%) had fetal distress but all fetuses were born alive without neonatal asphyxia. With regards to delivery mode, 9 pregnancies were terminated by cesarean section.
LESSON
Early anticoagulant treatment with LWMHs may improve pregnancy outcomes. The timing and mode of termination of pregnancy should be determined according to the condition of the mother and the fetus along with the gestational age.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Aged; Infant; Cesarean Section; Retrospective Studies; Umbilical Arteries; Ultrasonography, Prenatal; Pregnancy Outcome; Gestational Age; Thrombosis; Heparin, Low-Molecular-Weight
PubMed: 37058068
DOI: 10.1097/MD.0000000000033501 -
Archives of Iranian Medicine Jul 2022
Topics: Humans; Subclavian Artery; COVID-19; Thrombosis; Peripheral Arterial Disease
PubMed: 36404516
DOI: 10.34172/aim.2022.78 -
International Journal of Nanomedicine 2023Carotid artery thrombosis is the leading cause of stroke. Since there are no apparent symptoms in the early stages of carotid atherosclerosis onset, it causes a more...
BACKGROUND
Carotid artery thrombosis is the leading cause of stroke. Since there are no apparent symptoms in the early stages of carotid atherosclerosis onset, it causes a more significant clinical diagnosis. Photoacoustic (PA) imaging provides high contrast and good depth information, which has been used for the early detection and diagnosis of many diseases.
METHODS
We investigated thrombus formation by using 20% ferric chloride (FeCl) in the carotid arteries of KM mice for the thrombosis model. The near-infrared selenium/polypyrrole (Se@PPy) nanomaterials are easy to synthesize and have excellent optical absorption in vivo, which can be used as PA contrast agents to obtain thrombosis information.
RESULTS
In vitro experiments showed that Se@PPy nanocomposites have fulfilling PA ability in the 700 nm to 900 nm wavelength range. In the carotid atherosclerosis model, maximum PA signal enhancement up to 3.44, 4.04, and 5.07 times was observed by injection of Se@PPy nanomaterials, which helped to diagnose the severity of carotid atherosclerosis.
CONCLUSION
The superior PA signal of Se@PPy nanomaterials can identify the extent of atherosclerotic carotid lesions, demonstrating the feasibility of PA imaging technology in diagnosing carotid thrombosis lesion formation. This study demonstrates nanocomposites and PA techniques for imaging and diagnosing carotid thrombosis in vivo.
Topics: Animals; Mice; Selenium; Polymers; Nanospheres; Carotid Artery Thrombosis; Photoacoustic Techniques; Pyrroles; Carotid Arteries; Thrombosis; Carotid Artery Diseases; Atherosclerosis
PubMed: 37520300
DOI: 10.2147/IJN.S404743 -
Cardiovascular and Interventional... Mar 2017To report the real-world incidence and risk factors of stent thrombosis in the aortoiliac and femoropopliteal arteries in case of bare nitinol stent (BNS) or covered...
PURPOSE
To report the real-world incidence and risk factors of stent thrombosis in the aortoiliac and femoropopliteal arteries in case of bare nitinol stent (BNS) or covered nitinol stent (CNS) placement from a single-centre retrospective audit.
MATERIALS AND METHODS
Medical records of consecutive patients treated with peripheral stent placement for claudication or critical limb ischemia were audited for definite stent thrombosis defined as imaging confirmed stent thrombosis that presented as acute limb-threatening ischemia. Cases were stratified between aortoiliac and femoropopliteal anatomy. Cox regression analysis was employed to adjust for baseline clinical and procedural confounders and identify predictors of stent thrombosis and major limb loss.
RESULTS
256 patients (n = 277 limbs) were analysed over a 5-year period (2009-2014) including 117 aortoiliac stents (34 CNS; 12.8 ± 5.0 cm and 83 BNS; 7.8 ± 4.0 cm) and 160 femoropopliteal ones (60 CNS; 21.1 ± 11.0 cm and 100 BNS; 17.5 ± 11.9 cm). Median follow-up was 1 year. Overall stent thrombosis rate was 6.1% (17/277) after a median of 43 days (range 2-192 days) and affected almost exclusively the femoropopliteal segment (12/60 in the CNS cohort vs. 4/100 in the BNS; p = 0.001). Annualized stent thrombosis rates (per 100 person-years) were 12.5% in case of CNS and 1.4% in case of BNS (HR 6.3, 95% CI 2.4-17.9; p = 0.0002). Corresponding major amputations rates were 8.7 and 2.5%, respectively (HR 4.5, 95% CI 2.7-27.9; p = 0.0006). On multivariable analysis, critical leg ischemia and CNS placement were the only predictors of stent thrombosis. Diabetes, critical leg ischemia, femoropopliteal anatomy, long stents and CNS were independent predictors of major amputations.
CONCLUSIONS
Placement of long femoropopliteal covered nitinol stents is associated with an increased incidence of acute stent thrombosis and ensuing major amputation. Risks are significantly lower in the aortoiliac vessels and with use of bare nitinol stents.
Topics: Acute Disease; Aged; Alloys; Amputation, Surgical; Aorta; Causality; Comorbidity; Constriction, Pathologic; Extremities; Female; Femoral Artery; Follow-Up Studies; Humans; Incidence; Intermittent Claudication; Ischemia; Male; Peripheral Arterial Disease; Popliteal Artery; Prosthesis Design; Prosthesis Failure; Retrospective Studies; Risk Factors; Stents; Thrombosis; Time Factors; Treatment Outcome; Vascular Patency
PubMed: 27921154
DOI: 10.1007/s00270-016-1513-0 -
Journal of the... 2016Angiotensin converting enzyme inhibitors and propofol both exert hypotensive action and may affect hemostasis. We investigated the influence of quinapril and propofol on...
Angiotensin converting enzyme inhibitors and propofol both exert hypotensive action and may affect hemostasis. We investigated the influence of quinapril and propofol on hemodynamics and hemostasis in renal-hypertensive rats with induced arterial thrombosis. Two-kidney, one clip hypertensive rats were treated with quinapril (3.0 mg/kg for 10 days), and then received propofol infusion (15 mg/kg/h) during ongoing arterial thrombosis. The hemodynamic and hemostatic parameters were assayed. Quinapril exerted a hypotensive effect increasing after propofol infusion. Quinapril showed an antithrombotic effect with the platelet adhesion reduction, fibrinolysis enhancement and oxidative stress reduction. Propofol did not influence thrombosis; however, it inhibited fibrinolysis and showed prooxidative action. The effect of propofol on fibrinolysis and oxidative stress was significantly lower in quinapril-pretreated rats. Mortality was increased among rats treated with both drugs together. Our study demonstrates that pretreatment with quinapril reduced the adverse effects of propofol on hemostasis. Unfortunately, co-administration of both drugs potentiated hypotension in rats, which corresponds to higher mortality.
Topics: Animals; Antifibrinolytic Agents; Aorta; Carotid Arteries; Hemodynamics; Hypertension; Male; NADPH Oxidases; Nitric Oxide; Oxidants; Oxidative Stress; Platelet Adhesiveness; Propofol; Quinapril; Rats, Wistar; Regional Blood Flow; Superoxide Dismutase; Survival Analysis; Tetrahydroisoquinolines; Thrombosis
PubMed: 27169890
DOI: 10.1177/1470320316647239 -
Journal of Postgraduate Medicine 2023Mesenteric vascular thrombosis, typically of the superior mesenteric artery, is a frequent occurrence in patients with hypercoagulable conditions. Isolated involvement...
Mesenteric vascular thrombosis, typically of the superior mesenteric artery, is a frequent occurrence in patients with hypercoagulable conditions. Isolated involvement of the celiac artery is rare. Patients with celiac artery thrombosis can present with an acute abdomen or occasionally with acid peptic symptoms. A delay in diagnosis is associated with high rates of morbidity and mortality. We present a rare case of splenic infarction with celiac trunk thrombosis in a 54-year-old patient with underlying antiphospholipid (APLA) syndrome who presented with epigastric pain that was mistaken for symptoms of acid reflux.
Topics: Humans; Middle Aged; Celiac Artery; Abdomen, Acute; Mesenteric Artery, Superior; Thrombosis; Abdominal Pain
PubMed: 37530377
DOI: 10.4103/jpgm.jpgm_331_23 -
Arteriosclerosis, Thrombosis, and... Sep 2020Quantitative relationships between the extent of injury and thrombus formation in vivo are not well understood. Moreover, it has not been investigated how increased...
OBJECTIVE
Quantitative relationships between the extent of injury and thrombus formation in vivo are not well understood. Moreover, it has not been investigated how increased injury severity translates to blood-flow modulation. Here, we investigated interconnections between injury length, clot growth, and blood flow in a mouse model of laser-induced thrombosis. Approach and Results: Using intravital microscopy, we analyzed 59 clotting events collected from the cremaster arteriole of 14 adult mice. We regarded injury length as a measure of injury severity. The injury caused transient constriction upstream and downstream of the injury site resulting in a 50% reduction in arteriole diameter. The amount of platelet accumulation and fibrin formation did not depend on arteriole diameter or deformation but displayed an exponentially increasing dependence on injury length. The height of the platelet clot depended linearly on injury length and the arteriole diameter. Upstream arteriolar constriction correlated with delayed upstream velocity increase, which, in turn, determined downstream velocity. Before clot formation, flow velocity positively correlated with the arteriole diameter. After the onset of thrombus growth, flow velocity at the injury site negatively correlated with the arteriole diameter and with the size of the above-clot lumen.
CONCLUSIONS
Injury severity increased platelet accumulation and fibrin formation in a persistently steep fashion and, together with arteriole diameter, defined clot height. Arterial constriction and clot formation were characterized by a dynamic change in the blood flow, associated with increased flow velocity.
Topics: Abdominal Muscles; Animals; Arterioles; Blood Coagulation; Blood Flow Velocity; Blood Platelets; Constriction, Pathologic; Disease Models, Animal; Fibrin; Intravital Microscopy; Male; Mice; Microscopy, Fluorescence; Severity of Illness Index; Thrombosis; Time Factors; Vascular System Injuries
PubMed: 32640902
DOI: 10.1161/ATVBAHA.120.314786 -
Blood Oct 2017Regulated reorganization of the actin cytoskeleton is a prerequisite for proper platelet production and function. Consequently, defects in proteins controlling actin...
Regulated reorganization of the actin cytoskeleton is a prerequisite for proper platelet production and function. Consequently, defects in proteins controlling actin dynamics have been associated with platelet disorders in humans and mice. Twinfilin 2a (Twf2a) is a small actin-binding protein that inhibits actin filament assembly by sequestering actin monomers and capping filament barbed ends. Moreover, Twf2a binds heterodimeric capping proteins, but the role of this interaction in cytoskeletal dynamics has remained elusive. Even though Twf2a has pronounced effects on actin dynamics in vitro, only little is known about its function in vivo. Here, we report that constitutive Twf2a-deficient mice () display mild macrothrombocytopenia due to a markedly accelerated platelet clearance in the spleen. platelets showed enhanced integrin activation and α-granule release in response to stimulation of (hem) immunoreceptor tyrosine-based activation motif (ITAM) and G-protein-coupled receptors, increased adhesion and aggregate formation on collagen I under flow, and accelerated clot retraction and spreading on fibrinogen. In vivo, Twf2a deficiency resulted in shortened tail bleeding times and faster occlusive arterial thrombus formation. The hyperreactivity of platelets was attributed to enhanced actin dynamics, characterized by an increased activity of n-cofilin and profilin 1, leading to a thickened cortical cytoskeleton and hence sustained integrin activation by limiting calpain-mediated integrin inactivation. In summary, our results reveal the first in vivo functions of mammalian Twf2a and demonstrate that Twf2a-controlled actin rearrangements dampen platelet activation responses in a n-cofilin- and profilin 1-dependent manner, thereby indirectly regulating platelet reactivity and half-life in mice.
Topics: Actin Cytoskeleton; Animals; Apoptosis; Arteries; Blood Platelets; Integrins; Mice; Microfilament Proteins; Thrombocytopenia; Thrombosis
PubMed: 28743718
DOI: 10.1182/blood-2017-02-770768