Effects of a single bout of strenuous exercise on platelet activation in female ApoE/LDLR<sup>−/−</sup>mice

Przyborowski, Kamil; Kassassir, Hassan; Wojewoda, Marta; Kmiecik, Katarzyna; Sitek, Barbara; Siewiera, Karolina; Zakrzewska, Agnieszka; Rudolf, Agata M.; Kostogrys, Renata B.; Watała, Cezary; Zoladz, Jerzy A.; Chłopicki, Stefan

doi:10.1080/09537104.2016.1254764

Cited by 16 publications

(12 citation statements)

References 54 publications

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“…In our study, we used low-dose ASA (12 mg�kg -1 of body weight per day equivalent to~100 mg per day in humans [1]) for long-term treatment to achieve selective inhibition of COX-1-dependent thromboxane A 2 generation in platelets without inhibition of COX-1 and COX-2 elsewhere. The treatment with 12 mg�kg -1 of ASA decreased platelet-dependent TXB 2 generation in breast cancer-bearing mice in the ex vivo assay of stirred blood (Fig 1A) that allows for highly sensitive assessment of platelet activation, as reported by us previously [21]. However, the inhibitory effect of ASA on TXB 2 production and platelet reactivity was not detected in other assays ( Figs 1B, 1C and 3).…”

Section: Plos Onesupporting

confidence: 69%

“…Sample preparation. Blood samples were diluted with saline (5 times) and stirred in alternating directions in 1ml cuvettes with disposable, siliconised stir bars (Chrono-Log, US) for one hour at 37˚C (1,500 rpm; spinning time in one direction: 3 s; acceleration/deceleration: 20,000 rpm�s -1 ) in a specially designed Xyzyk apparatus (Xyzyk Co, Poland), as described previously [21]. To determine the generation of eicosanoids ex vivo in the stirred blood, samples were taken on aspirin (500 μM) after 60 minutes of ex vivo stirring in Xyzyk apparatus and centrifuged to obtain plasma (3000xg, 12 min, 4˚C).…”

Section: Measurement Of Eicosanoid Production By Lc-ms/msmentioning

confidence: 99%

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Unexpected effects of long-term treatment with acetylsalicylic acid on late phase of pulmonary metastasis in murine model of orthotopic breast cancer

et al. 2020

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Long-term administration of acetylsalicylic acid (ASA) was effective in prevention of colorectal cancer, whereas the efficacy of this compound in other cancer types, including breast cancer, has been less convincingly documented. Indeed, the antimetastatic effect of lowdose ASA was observed only in the early intravascular phase of metastasis of breast cancer. In the present work, we characterized the effects of long-term treatment with ASA on the late phase of pulmonary metastasis in a mouse orthotopic 4T1 breast cancer model. Mice were treated with ASA at a dose of 12 mg�kg-1 of body weight daily starting one week prior to inoculation of 4T1 breast cancer cells, and the treatment was continued throughout progression of the disease. ASA administration decreased platelet TXB 2 production in ex vivo assays but did not change thrombin-induced platelet reactivity. Although the number of metastases in the lungs remained unchanged in ASA-treated mice, infiltration of inflammatory cells was increased concomitantly with higher G-CSF and serotonin concentrations in the lungs. Pulmonary NO production was compromised compared to control 4T1 mice. ASA treatment also evoked an increase in platelet and granulocyte counts and decreased systemic NO bioavailability along with increased markers of systemic oxidant stress such as higher GSSG/lower GSH concentrations in RBC. Analysis of eicosanoids in stirred blood demonstrated that administration of ASA at a dose of 12 mg�kg-1 to cancer-bearing mice had an effect beyond inhibition of platelet COX-1, suggesting long-term treatment with lowdose aspirin is not a selective murine platelet COX-1/TXA 2 pathway inhibitor in cancer-bearing mice. In summary, quite surprisingly, long-term treatment with low-dose ASA administered until the advanced phase of breast cancer in a murine orthotopic model of 4T1 breast cancer negatively affected the phenotype of the disease.

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Section: Plos Onesupporting

confidence: 69%

Section: Measurement Of Eicosanoid Production By Lc-ms/msmentioning

confidence: 99%

Unexpected effects of long-term treatment with acetylsalicylic acid on late phase of pulmonary metastasis in murine model of orthotopic breast cancer

et al. 2020

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“…Blood samples were diluted with saline (5 times) and stirred in alternating directions in 1ml cuvettes with disposable, siliconized stir bars (Chrono-Log, US) for one hour in 37°C (1500rpm; spinning time in one direction: 3s; acceleration/deceleration: 20000 rpm·s -1 ) in a specially-designed Xyzyk apparatus (Xyzyk Co, Poland), as described previously [ 48 ]. To determine basal and mechanically-stimulated ex vivo TXB 2 generation in diluted blood, samples were taken on aspirin (500 μM) at the 2 nd and 60 th minute of ex vivo stirring of blood samples and centrifuged to obtain plasma (3000xg, 12 min, 4°C).…”

Section: Methodsmentioning

confidence: 99%

Dual antiplatelet therapy with clopidogrel and aspirin increases mortality in 4T1 metastatic breast cancer-bearing mice by inducing vascular mimicry in primary tumour

et al. 2018

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Platelet inhibition has been considered an effective strategy for combating cancer metastasis and compromising disease malignancy although recent clinical data provided evidence that long-term platelet inhibition might increase incidence of cancer deaths in initially cancer-free patients. In the present study we demonstrated that dual anti-platelet therapy based on aspirin and clopidogrel (ASA+Cl), a routine regiment in cardiovascular patients, when given to cancer-bearing mice injected orthotopically with 4T1 breast cancer cells, promoted progression of the disease and reduced mice survival in association with induction of vascular mimicry (VM) in primary tumour. In contrast, treatment with ASA+Cl or platelet depletion did reduce pulmonary metastasis in mice, if 4T1 cells were injected intravenously. In conclusion, distinct platelet-dependent mechanisms inhibited by ASA+Cl treatment promoted cancer malignancy and VM in the presence of primary tumour and afforded protection against pulmonary metastasis in the absence of primary tumour. In view of our data, long-term inhibition of platelet function by dual anti-platelet therapy (ASA+Cl) might pose a hazard when applied to a patient with undiagnosed and untreated malignant cancer prone to undergo VM.

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“…Platelet reactivity was assessed according to a previously published protocol with modification . Briefly, subsequent to anesthesia, blood was collected on heparin from the right heart ventricle.…”

Section: Methodsmentioning

confidence: 99%

“…Platelet reactivity was assessed according to a previously published protocol with modification. 37 Briefly, subsequent to anesthesia, blood was collected on heparin from the right heart ventricle. Whole blood was diluted and either directly processed according to a "wash blood" protocol 38 or incubated at 37°C for 60 minutes, with constant stirring in a Xyzyk apparatus (Xyzyk Company, Krakow, Poland) and then processed according to the "wash blood" protocol.…”

Section: Systemic Platelet Reactivitymentioning

confidence: 99%

Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice

Adamski

Sternak

Mohaissen

et al. 2018

JAHA

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BackgroundAlthough advanced heart failure (HF) is a clinically documented risk factor for vascular cognitive impairment, the occurrence and pathomechanisms of vascular cognitive impairment in early stages of HF are equivocal. Here, we characterize vascular cognitive impairment in the early stages of HF development and assess whether cerebral hypoperfusion or prothrombotic conditions are involved.Methods and ResultsTgαq*44 mice with slowly developing isolated HF triggered by cardiomyocyte‐specific overexpression of G‐αq*44 protein were studied before the end‐stage HF, at the ages of 3, 6, and 10 months: before left ventricle dysfunction; at the stage of early left ventricle diastolic dysfunction (with preserved ejection fraction); and left ventricle diastolic/systolic dysfunction, respectively. In 6‐ to 10‐month‐old but not in 3‐month‐old Tgαq*44 mice, behavioral and cognitive impairment was identified with compromised blood‐brain barrier permeability, most significantly in brain cortex, that was associated with myelin sheet loss and changes in astrocytes and microglia. Brain endothelial cells displayed increased E‐selectin immunoreactivity, which was accompanied by increased amyloid‐β1‐42 accumulation in piriform cortex and increased cortical oxidative stress (8‐OHdG immunoreactivity). Resting cerebral blood flow measured by magnetic resonance imaging in vivo was preserved, but ex vivo NO‐dependent cortical arteriole flow regulation was impaired. Platelet hyperreactivity was present in 3‐ to 10‐month‐old Tgαq*44 mice, but it was not associated with increased platelet‐dependent thrombogenicity.ConclusionsWe report for the first time that vascular cognitive impairment is already present in the early stage of HF development, even before left ventricle systolic dysfunction. The underlying pathomechanism, independent of brain hypoperfusion, involves preceding platelet hyperreactivity and brain endothelium inflammatory activation.

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Effects of a single bout of strenuous exercise on platelet activation in female ApoE/LDLR^−/−mice

Cited by 16 publications

References 54 publications

Unexpected effects of long-term treatment with acetylsalicylic acid on late phase of pulmonary metastasis in murine model of orthotopic breast cancer

Unexpected effects of long-term treatment with acetylsalicylic acid on late phase of pulmonary metastasis in murine model of orthotopic breast cancer

Dual antiplatelet therapy with clopidogrel and aspirin increases mortality in 4T1 metastatic breast cancer-bearing mice by inducing vascular mimicry in primary tumour

Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice

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Effects of a single bout of strenuous exercise on platelet activation in female ApoE/LDLR−/−mice

Cited by 16 publications

References 54 publications

Unexpected effects of long-term treatment with acetylsalicylic acid on late phase of pulmonary metastasis in murine model of orthotopic breast cancer

Unexpected effects of long-term treatment with acetylsalicylic acid on late phase of pulmonary metastasis in murine model of orthotopic breast cancer

Dual antiplatelet therapy with clopidogrel and aspirin increases mortality in 4T1 metastatic breast cancer-bearing mice by inducing vascular mimicry in primary tumour

Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice

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Effects of a single bout of strenuous exercise on platelet activation in female ApoE/LDLR^−/−mice