GW24-e2354 Effect of Xiongshao Capsule on the platelet activation level and platelet gelsolin in rat model of Acute Myocardial infarctionin vivo

The biological role of platelet gelsolin in platelet activation of acute myocardial infarction is not defined. In order to provide a potential new antiplatelet target for Chinese medicine and to elucidate the contribution of Xiongshao capsule, the effective components of Chuanxiong rhizome and red peony root, in this study, we randomly allocated Sprague Dawley rats to left anterior descending coronary artery ligation or sham surgery and different drug prophylaxis as control. We found that gelsolin is highly expressed in platelet rich plasma and lowly expressed in platelet poor plasma, accompanied by the high platelet activation level in model rats; plasma actin filaments and mean fluorescence intensity (MFI) of platelet calcium ion increased and plasma vitamin D binding protein decreased in model rats. Xiongshao capsule could inhibit the gelsolin expression in platelet rich plasma and ischemic heart tissue simultaneously and reduce the level of plasma F-actin and MFI of platelet calcium ion. Our study concludes that platelet gelsolin is an important contributor to platelet activation, and platelet gelsolin inhibition may form a novel target for antiplatelet therapy. Xiongshao capsule may be a promising Chinese medicine drug for antiplatelet and aspirin-like cardioprotection effect.

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Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots

Metabolites ◽

10.3390/metabo11060354 ◽

2021 ◽

Vol 11 (6) ◽

pp. 354

Author(s):

Rustem I. Litvinov ◽

Alina D. Peshkova ◽

Giang Le Minh ◽

Nail N. Khaertdinov ◽

Natalia G. Evtugina ◽

...

Keyword(s):

Flow Cytometry ◽

Platelet Activation ◽

Rat Model ◽

Binding Capacity ◽

Blood Clot ◽

Fibrinogen Binding ◽

Blood Clots ◽

Clot Contraction ◽

Dose Dependent

Hyperhomocysteinemia (HHcy) is associated with thrombosis, but the mechanistic links between them are not understood. We studied effects of homocysteine (Hcy) on clot contraction in vitro and in a rat model of HHcy. Incubation of blood with exogenous Hcy for 1 min enhanced clot contraction, while 15-min incubation led to a dose-dependent suppression of contraction. These effects were likely due to direct Hcy-induced platelet activation followed by exhaustion, as revealed by an increase in fibrinogen-binding capacity and P-selectin expression determined by flow cytometry. In the blood of rats with HHcy, clot contraction was enhanced at moderately elevated Hcy levels (10–50 μM), while at higher Hcy levels (>50 μM), the onset of clot contraction was delayed. HHcy was associated with thrombocytosis combined with a reduced erythrocyte count and hypofibrinogenemia. These data suggest that in HHcy, platelets get activated directly and indirectly, leading to enhanced clot contraction that is facilitated by the reduced content and resilience of fibrin and erythrocytes in the clot. The excessive platelet activation can lead to exhaustion and impaired contractility, which makes clots larger and more obstructive. In conclusion, HHcy modulates blood clot contraction, which may comprise an underappreciated pro- or antithrombotic mechanism.

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Abstract P551: Platelet Activation is Associated with Pulmonary Edema and Renal Injury in a Rat Model of Polymicrobial Sepsis

Hypertension ◽

10.1161/hyp.70.suppl_1.p551 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Jeanne Ishimwe ◽

Maggie L McCalmon ◽

Corbin A Shields ◽

Ashley Gnam ◽

Jan M Williams ◽

...

Keyword(s):

Renal Function ◽

Pulmonary Edema ◽

Organ Dysfunction ◽

Platelet Activation ◽

Rat Model ◽

Renal Injury ◽

Cecal Ligation ◽

Cecal Ligation And Puncture ◽

Activated Platelets ◽

Underlying Mechanisms

Sepsis, life-threatening organ dysfunction due to a dysregulated host response to infection, is positively correlated with platelet activation. Furthermore, clinical studies have also shown that platelet activation is associated with sepsis severity, suggesting a role for platelets in sepsis pathophysiology. Despite this correlation, the underlying mechanisms by which activated platelets contribute to sepsis are under investigated. In preliminary studies, we set out to determine if platelet activation is associated with multi-organ dysfunction and injury in a rat model of chronic polymicrobial abdominal sepsis. Sepsis was induced via cecal ligation and puncture (CLP) followed by cecum removal 24 hours post-CLP. At 72 hours post-CLP, blood, urine, and tissues were collected for analysis. Platelet activation was measured via flow cytometry. Lung wet/dry ratio and plasma creatinine were measured to assess lung edema and renal injury, respectively. Platelet activation doubled in CLP rats versus Sham rats. Activated platelets increased from 3.8±1.7% of the gated population in Sham animals (n=5) to 9.2±1.9% of the gated population in CLP animals (n=5; p=0.07). Lung wet/dry ratio significantly increased from 3.9±0.2 in Sham (n=8) to 6.7±1 in CLP rats (n=8; p<0.05). Furthermore, plasma creatinine increased by 33% from 0.55±0.3 mg/dL in Sham animals (n=6) to 0.73±0.06 mg/dL in CLP rats (n=8; p<0.05), indicating a decrease in renal function. These data demonstrate, for the first time, an increase in platelet activation in response to CLP, and identifies an association of activated platelets with pulmonary edema and reduced renal function in the cecal ligation and puncture rat model of abdominal polymicrobial sepsis. Future studies will investigate the underlying mechanisms by which activated platelets contribute to multi-organ dysfunction and injury in sepsis.

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Bubble-induced platelet aggregation in a rat model of decompression sickness

Journal of Applied Physiology ◽

10.1152/japplphysiol.91644.2008 ◽

2009 ◽

Vol 107 (6) ◽

pp. 1825-1829 ◽

Cited By ~ 30

Author(s):

Jean-Michel Pontier ◽

Nicolas Vallée ◽

Lionel Bourdon

Keyword(s):

Platelet Count ◽

Platelet Aggregation ◽

Platelet Activation ◽

Rat Model ◽

Thrombin Generation ◽

Decompression Sickness ◽

Coagulation Cascade ◽

Coagulation System ◽

Control Group ◽

Hyperbaric Exposure

Previous studies have highlighted that bubble-induced platelet aggregation is a predictor index of decompression sickness (DCS) severity in animals and bubble formation after a single air dive in humans. The present study attempted to investigate plasmatic indexes of the coagulation system and platelet activation in our rat model of DCS. Male Sprague-Dawley rats were assigned to one experimental group with a hyperbaric exposure and one control group maintained at atmospheric pressure. Rats were compressed to 1,000 kPa (90 m saltwater) for 45 min while breathing air. The onset of death time and DCS symptoms were recorded during a 30-min observed period after rats had surfaced. Plasmatic indexes were platelet factor 4 (PF4) for platelet activation, soluble glycoprotein V (sGPV) for thrombin generation, and thrombin-antithrombin complexes for the coagulation system. Blood samples for a platelet count and markers were taken 3 wk before the experimental protocol and within the 30 min after rats had surfaced. We confirmed a correlation between the percent fall in platelet count and DCS severity. Plasmatic levels of sGPV and PF4 were significantly increased after the hyperbaric exposure, with no change in the control group. The present study confirms platelet consumption as a potential index for evaluating decompression stress and DCS severity. The results point to the participation of thrombin generation in the coagulation cascade and platelet activation in bubble-induced platelet aggregation. In our animal model of DCS, the results cannot prejudge the mechanisms of platelet activation between bubble-induced vessel wall injury and bubble-blood component interactions.

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Indoxyl Sulfate Promotes Arterial Thrombosis in Rat Model via Increased Levels of Complex TF/VII, PAI-1, Platelet Activation as Well as Decreased Contents of SIRT1 and SIRT3

Frontiers in Physiology ◽

10.3389/fphys.2018.01623 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 12

Author(s):

Malgorzata Karbowska ◽

Tomasz W. Kaminski ◽

Beata Znorko ◽

Tomasz Domaniewski ◽

Tomasz Misztal ◽

...

Keyword(s):

Platelet Activation ◽

Rat Model ◽

Arterial Thrombosis ◽

Indoxyl Sulfate ◽

Pai 1

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Circulating platelet-neutrophil aggregates as risk factor for deep venous thrombosis

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2018-0909 ◽

2019 ◽

Vol 57 (5) ◽

pp. 707-715 ◽

Cited By ~ 1

Author(s):

Jingyi Zhou ◽

Erwen Xu ◽

Kang Shao ◽

Wenyan Shen ◽

Yi Gu ◽

...

Keyword(s):

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Platelet Activation ◽

Elevated Level ◽

Inflammatory Diseases ◽

Control Group ◽

Activation Level ◽

Blood Smears ◽

Inflammatory Processes ◽

Suitable Marker

Abstract Background Platelet-neutrophil aggregates (PNAs) are fundamental mechanisms linking hemostasis and inflammatory processes. Elevated level of PNAs have been reported in inflammatory diseases and coronary artery diseases. However, studies on the correlation between PNAs formation and deep venous thrombosis (DVT) are not available. Methods A total of 92 participants were involved in this study, including 32 cases with DVT and 60 cases without DVT. Blood samples coagulated by K2-EDTA or sodium citrate were prepared for blood cell count and blood smears. PNAs and platelet activation were measured using flow cytometry. The correlation between platelet activation level and PNAs level was analyzed by linear regression. Receiver operating characteristic (ROC) analysis was performed, assessing the prognostic performance of PNAs to predict potential risk of DVT occurrence. Results PNAs was found in the blood smears of patients with DVT. Significant increased level of PNAs was identified in DVT group (medium 8.43%, interquartile range [IQR] 4.11%–15.69%), compared with that in control group (5.16%, IQR 2.40–9.60, p<0.01). The DVT group also showed a dramatic elevated level of total platelet activation (medium 16.06%, IQR 6.04–22.05) vs. control group (11.26%, IQR 5.54–19.99, p<0.05). The PNAs level was correlated with total platelet activation (r2=0.58, p<0.0001). A significantly high odds ratio (OR) of DVT occurrence was identified when the level of PNAs was higher than 7.4% (OR 3.60, 95% confidence interval [CI] 1.463–8.838, p<0.01). Conclusions An elevated level of PNAs was associated with risk of DVT occurrence, which might be a suitable marker predicting DVT development.

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