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  1. Article ; Online: LDL-Cholesterol and Platelets

    Aleksandra Gąsecka / Sylwester Rogula / Łukasz Szarpak / Krzysztof J. Filipiak

    Life, Vol 11, Iss 1, p

    Insights into Their Interactions in Atherosclerosis

    2021  Volume 39

    Abstract: Atherosclerosis and its complications, including acute coronary syndromes, are the major cause of death worldwide. The two most important pathophysiological mechanisms underlying atherosclerosis include increased platelet activation and increased low- ... ...

    Abstract Atherosclerosis and its complications, including acute coronary syndromes, are the major cause of death worldwide. The two most important pathophysiological mechanisms underlying atherosclerosis include increased platelet activation and increased low-density lipoproteins (LDL) concentration. In contrast to LDL, oxidized (ox)-LDL have direct pro-thrombotic properties by functional interactions with platelets, leading to platelet activation and favoring thrombus formation. In this review, we summarize the currently available evidence on the interactions between LDL-cholesterol and platelets, which are based on (i) the presence of ox-LDL-binding sites on platelets, (ii) generation of ox-LDL by platelets and (iii) the role of activated platelets and ox-LDL in atherosclerosis. In addition, we elaborate on the clinical implications of these interactions, including development of the new therapeutic possibilities. The ability to understand and modulate mechanisms governing interactions between LDL-cholesterol and platelets may offer new treatment strategies for atherosclerosis prevention.
    Keywords LDL-cholesterol ; platelets ; extracellular vesicles ; atherosclerosis ; treatment ; Science ; Q
    Subject code 630
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Safety and Efficacy of DOACs in Patients with Advanced and End-Stage Renal Disease

    Sylwester Rogula / Aleksandra Gąsecka / Tomasz Mazurek / Eliano Pio Navarese / Łukasz Szarpak / Krzysztof J. Filipiak

    International Journal of Environmental Research and Public Health, Vol 19, Iss 1436, p

    2022  Volume 1436

    Abstract: The prevalence of chronic kidney disease (CKD) is increasing due to the aging of the population and multiplication of risk factors, such as hypertension, arteriosclerosis and obesity. Impaired renal function increases both the risk of bleeding and ... ...

    Abstract The prevalence of chronic kidney disease (CKD) is increasing due to the aging of the population and multiplication of risk factors, such as hypertension, arteriosclerosis and obesity. Impaired renal function increases both the risk of bleeding and thrombosis. There are two groups of orally administered drugs to prevent thromboembolic events in patients with CKD who require anticoagulation: vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). Although VKAs remain the first-line treatment in patients with advanced CKD, treatment with VKAs is challenging due to difficulties in maintaining the appropriate anticoagulation level, tendency to accelerate vascular calcification and faster progression of CKD in patients treated with VKAs. On the other hand, the pleiotropic effect of DOACs, including vascular protection and anti-inflammatory properties along with comparable efficacy and safety of treatment with DOACs, compared to VKAs observed in preliminary reports encourages the use of DOACs in patients with CKD. This review summarizes the available data on the efficacy and safety of DOACs in patients with CKD and provides recommendations regarding the choice of the optimal drug and dosage depending on the CKD stage.
    Keywords direct oral anticoagulants ; chronic kidney disease ; end-stage renal disease ; anticoagulation ; hemodialysis ; DOAC ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Inclisiran—Silencing the Cholesterol, Speaking up the Prognosis

    Sylwester Rogula / Ewelina Błażejowska / Aleksandra Gąsecka / Łukasz Szarpak / Milosz J. Jaguszewski / Tomasz Mazurek / Krzysztof J. Filipiak

    Journal of Clinical Medicine, Vol 10, Iss 2467, p

    2021  Volume 2467

    Abstract: The reduction of circulating low-density lipoprotein-cholesterol (LDL-C) is a primary target in cardiovascular risk reduction due to its well-established benefits in terms of decreased mortality. Despite the use of statin therapy, 10%–20% of high- and ... ...

    Abstract The reduction of circulating low-density lipoprotein-cholesterol (LDL-C) is a primary target in cardiovascular risk reduction due to its well-established benefits in terms of decreased mortality. Despite the use of statin therapy, 10%–20% of high- and very-high-risk patients do not reach their LDL-C targets. There is an urgent need for improved strategies to manage dyslipidemia, especially among patients with homozygous familial hypercholesterolemia, but also in patients with established cardiovascular disease who fail to achieve LDL goals despite combined statin, ezetimibe, and PCSK9 inhibitor (PCSK9i) therapy. Inclisiran is a disruptive, first-in-class small interfering RNA (siRNA)-based therapeutic developed for the treatment of hypercholesterolemia that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) synthesis, thereby upregulating the number of LDL receptors on the hepatocytes, thus lowering the plasma LDL-C concentration. Inclisiran decreases the LDL-C levels by over 50% with one dose every 6 months, making it a simple and well-tolerated treatment strategy. In this review, we summarize the general information regarding (i) the role of LDL-C in atherosclerotic cardiovascular disease, (ii) data regarding the role of PCSK9 in cholesterol metabolism, (iii) pleiotropic effects of PCSK9, and (iv) the effects of PCSK9 silencing. In addition, we focus on inclisiran, in terms of its (i) mechanism of action, (ii) biological efficacy and safety, (iii) results from the ORION trials, (iv) benefits of its combination with statins, and (v) its potential future role in atherosclerotic cardiovascular disease.
    Keywords atherosclerosis ; cardiovascular disease ; hypercholesterolemia ; inclisiran ; siRNA ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Statins in COVID-19 Therapy

    Justyna Olszewska-Parasiewicz / Łukasz Szarpak / Sylwester Rogula / Aleksandra Gąsecka / Urszula Szymańska / Maria Kwiatkowska / Milosz J. Jaguszewski / Radosław Sierpiński / Artur Zaczyński / Waldemar Wierzba / Dariusz A. Kosior

    Life, Vol 11, Iss 565, p

    2021  Volume 565

    Abstract: Inhibitors of 3-hydroxy-3methylgultaryl-coenzyme A reductase (statins) are one of the main groups of drugs used in preventing and treating cardiovascular diseases worldwide. They are widely available, cheap, and well-tolerated. Based on statins’ ... ...

    Abstract Inhibitors of 3-hydroxy-3methylgultaryl-coenzyme A reductase (statins) are one of the main groups of drugs used in preventing and treating cardiovascular diseases worldwide. They are widely available, cheap, and well-tolerated. Based on statins’ pleiotropic properties, including improvement of endothelial dysfunction, antioxidant properties, atherosclerotic plaque stabilization, and inhibition of inflammatory responses, it can be hypothesized that the use of statins, at least as an adjuvant in antiviral therapy, may be justified. All these effects might be especially beneficial in patients with COVID-19, suffering from endothelial dysfunction, microvascular and macrovascular thrombosis, and cytokine storm. Here, we review the recent data regarding the pathophysiology of SARS-CoV-2 activity in host cells, proposed COVID-19 therapy, the pleiotropic activity of statins, and statins in clinical trials in respiratory infections. According to the guidelines of the European and American Cardiac Societies, in patients with cardiovascular disease or high cardiovascular risk with concomitant COVID-19 it is recommended to continue statin treatment. However, the initiation of statin therapy de novo in COVID-19 treatment should only be done as part of a clinical trial.
    Keywords COVID-19 ; SARS-CoV-2 ; pleiotropic effects ; statins ; therapy ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  5. Article ; Online: Prostacyclin Analogues Inhibit Platelet Reactivity, Extracellular Vesicle Release and Thrombus Formation in Patients with Pulmonary Arterial Hypertension

    Aleksandra Gąsecka / Marta Banaszkiewicz / Rienk Nieuwland / Edwin van der Pol / Najat Hajji / Hubert Mutwil / Sylwester Rogula / Wiktoria Rutkowska / Kinga Pluta / Ceren Eyileten / Marek Postuła / Szymon Darocha / Zenon Huczek / Grzegorz Opolski / Krzysztof J. Filipiak / Adam Torbicki / Marcin Kurzyna

    Journal of Clinical Medicine, Vol 10, Iss 5, p

    2021  Volume 1024

    Abstract: 1) Background: Prostacyclin analogues (epoprostenol, treprostinil, and iloprost) induce vasodilation in pulmonary arterial hypertension (PAH) but also inhibit platelet function. (2) Objectives: We assessed platelet function in PAH patients treated with ... ...

    Abstract (1) Background: Prostacyclin analogues (epoprostenol, treprostinil, and iloprost) induce vasodilation in pulmonary arterial hypertension (PAH) but also inhibit platelet function. (2) Objectives: We assessed platelet function in PAH patients treated with prostacyclin analogues and not receiving prostacyclin analogues. (3) Methods: Venous blood was collected from 42 patients treated with prostacyclin analogues (49.5 ± 15.9 years, 81% female) and 38 patients not receiving prostacyclin analogues (55.5 ± 15.6 years, 74% female). Platelet reactivity was analyzed by impedance aggregometry using arachidonic acid (AA; 0.5 mM), adenosine diphosphate (ADP; 6.5 µM), and thrombin receptor-activating peptide (TRAP; 32 µM) as agonists. In a subset of patients, concentrations of extracellular vesicles (EVs) from all platelets (CD61 + ), activated platelets (CD61 + /CD62P + ), leukocytes (CD45 + ), and endothelial cells (CD146 + ) were analyzed by flow cytometry. Platelet-rich thrombus formation was measured using a whole blood perfusion system. (4) Results: Compared to controls, PAH patients treated with prostacyclin analogues had lower platelet reactivity in response to AA and ADP ( p = 0.01 for both), lower concentrations of platelet and leukocyte EVs ( p ≤ 0.04), delayed thrombus formation ( p ≤ 0.003), and decreased thrombus size ( p = 0.008). Epoprostenol did not affect platelet reactivity but decreased the concentrations of platelet and leukocyte EVs ( p ≤ 0.04). Treprostinil decreased platelet reactivity in response to AA and ADP ( p ≤ 0.02) but had no effect on the concentrations of EVs. All prostacyclin analogues delayed thrombus formation and decreased thrombus size ( p ≤ 0.04). (5) Conclusions: PAH patients treated with prostacyclin analogues had impaired platelet reactivity, EV release, and thrombus formation, compared to patients not receiving prostacyclin analogues.
    Keywords extracellular vesicles ; platelet reactivity ; prostacyclin analogues ; pulmonary arterial hypertension ; thrombus formation ; Medicine ; R
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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