Sex-dependent effects of finerenone on hemostasis in normoglycemic and streptozotocin-induced diabetic mice.

Diabetes is associated with aldosterone excess and the overactivation of its mineralocorticoid receptor (MR) which leads to the development of many cardiovascular dysfunctions. Therefore, MR antagonists have been found to exert favorable effects on the cardiovascular system. Finerenone is a new nonsteroidal MR antagonist approved for the treatment of chronic kidney disease associated with type 2 diabetes.

PECAM-1/Thrombus Ratio Correlates with Blood Loss during Off-Pump Coronary Artery Bypass Grafting (OPCAB) Surgery: A Preliminary Study.

Platelet endothelial cell adhesion molecule 1 (PECAM-1) is considered an antiplatelet molecule. Previously, we introduced a new parameter called the PECAM-1/thrombus ratio, which indicates the proportion of PECAM-1 in the thrombus and provides a precise description of human platelet activity (in vitro). The aim of this study was to determine whether the PECAM-1/thrombus ratio could serve as a predictive factor for bleeding events during off-pump coronary artery bypass grafting (OPCAB).

Sex-dependent effects of canagliflozin and dapagliflozin on hemostasis in normoglycemic and hyperglycemic mice.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are antihyperglycemic drugs that decrease mortality from cardiovascular diseases. However, their effects on hemostasis in the cardioprotective effects have not been evaluated. Therefore, the effects of canagliflozin (CANA, 100 mg/kg, p.

Aldosterone Increases Vascular Permeability in Rat Skin.

The aim of this study was to evaluate the effect of acute aldosterone (ALDO) administration on the vascular permeability of skin. ALDO was injected intradermally into rats, and vascular permeability was measured. Eplerenone (EPL), a selective mineralocorticoid receptor (MR) antagonist, was used.

Antioxidant enzymes immobilized on gold and silver nanoparticles enhance DNA repairing systems of rat skin after exposure to ultraviolet radiation.

The aim of the study was to investigate in vivo whether the application of immobilized superoxide dismutase (SOD) and catalase (CAT) could enhance DNA repairing systems and reduce level of CPD (cyclobutane pyrimidine dimers) and 6-4PP ((6-4) pyrimidine-pyrimidone photoproducts), and whether the immobilization on gold (AuNPs) and silver (AgNPs) nanoparticles affects the outcome. The study presents secondary analysis of our previous research. Three-day application of SOD and CAT in all forms of solution decreased the levels of CPD and 6-4PP boosted by UV irradiation.

Tannins as Hemostasis Modulators.

The hemostasis system is often affected by complications associated with cardiovascular diseases, which results in thromboembolic events. Compounds of plant origin and plant extracts are considered as a promising source of substances that could modulate the functioning of the hemostasis system and thus reduce the risk of thromboembolism. Among them, tannins, which are plant-origin compounds with potential effects in hemostasis, deserve a special mention.

Peanut-Shaped Gold Nanoparticles with Shells of Ceragenin CSA-131 Display the Ability to Inhibit Ovarian Cancer Growth In Vitro and in a Tumor Xenograft Model.

Gold nanoparticles-assisted delivery of antineoplastics into cancerous cells is presented as an effective approach for overcoming the limitations of systemic chemotherapy. Although ceragenins show great potential as anti-cancer agents, in some tumors, effective inhibition of cancer cells proliferation requires application of ceragenins at doses within their hemolytic range. For the purpose of toxicity/efficiency ratio control, peanut-shaped gold nanoparticles (AuP NPs) were functionalized with a shell of ceragenin CSA-131 and the cytotoxicity of AuP@CSA-131 against ovarian cancer SKOV-3 cells and were then analyzed.

Enhanced Thrombotic Responses Are Associated With Striatin Deficiency and Aldosterone.

Background In addition to its role on blood pressure, aldosterone (ALDO) also affects the hemostatic system leading to increased experimental thrombosis. Striatin is an intermediate in the rapid, nongenomic actions of ALDO. Striatin heterozygote knockout () mice have salt sensitivity of blood pressure and mildly chronically increased ALDO levels.

Utility of Platelet Endothelial Cell Adhesion Molecule 1 in the Platelet Activity Assessment in Mouse and Human Blood.

In our previous study, we introduced the platelet endothelial cell adhesion molecule 1 (PECAM-1)/thrombus ratio, which is a parameter indicating the proportion of PECAM-1 in laser-induced thrombi in mice. Because PECAM-1 is an antithrombotic molecule, the higher the PECAM-1/thrombus ratio, the less activated the platelets. In this study, we used an extracorporeal model of thrombosis (flow chamber model) to verify its usefulness in the assessment of the PECAM-1/thrombus ratio in animal and human studies.

ROS-Mediated Apoptosis and Autophagy in Ovarian Cancer Cells Treated with Peanut-Shaped Gold Nanoparticles.

Background: Even with considerable improvement in treatment of epithelial ovarian cancer achieved in recent years, an increasing chemotherapy resistance and disease 5-year relapse is recorded for a majority part of patients that encourages the search for better therapeutic options. Gold nanoparticles (Au NPs) due to plethora of unique physiochemical features are thoroughly tested as drug delivery, radiosensitizers, as well as photothermal and photodynamic therapy agents. Importantly, due to highly controlled synthesis, it is possible to obtain nanomaterials with directed size and shape.

Hyperglycemia Potentiates Prothrombotic Effect of Aldosterone in a Rat Arterial Thrombosis Model.

We investigated the role of aldosterone (ALDO) in the development of arterial thrombosis in streptozotocin-induced diabetic rats. To evaluate the effect of endogenous ALDO, the rats underwent adrenalectomy (ADX). ADX reduced the development of arterial thrombosis.

HAuCl, Putative General Aquaporins Blocker, Reduces Platelet Spreading, Filopodia Formation, Procoagulant Response, and Thrombus Formation Under Flow.

: Recent studies indicate that aquaporin (AQP) water channels have a regulatory function in human platelet secretion and in procoagulant response of murine platelets. However, the engagement of AQPs in morphological changes, procoagulant response, and thrombus formation in human blood has never been investigated. : Confocal microscopy was used to study platelet spreading, filopodia formation, ballooning, and thrombus formation under flow.

The effect of immobilized antioxidant enzymes on the oxidative stress in UV-irradiated rat skin.

Superoxide dismutase (SOD) and catalase (CAT) immobilized on gold nanoparticles (AuNP) and silver nanoparticles (AgNP) nanoparticles were used to reduce UV radiation-induced oxidative stress in rat skin. The antioxidant influence of the enzymes was investigated on level of malondialdehyde, 8-hydroksy-2'deoksyguanozine, myeloperoxidase, total antioxidant capacity, SOD2 and CAT activity and expression, and glutathione and glutathione peroxidase activity. The application of immobilized SOD and CAT on UV-irradiated skin reduced malondialdehyde and 8-hydroksy-2'deoksyguanozine levels also SOD and CAT activity and expression increased.

New approaches for the assessment of platelet activation status in thrombus under flow condition using confocal microscopy.

The goal of the study was the assessment of heterogeneous platelet activation status in thrombus. In a ferric(III) chloride (FeCl) thrombosis (intravital) model of C57BL/6 J mice, the area of irreversibly activated (phosphatidylserine (PS)-positive) platelets was assessed after 1-s exposure of a vessel to FeCl. In a laser-induced thrombosis (intravital) model of GFP mice, the area of the thrombus composed of PS-negative platelets was evaluated.

Rapid effects of aldosterone on platelets, coagulation, and fibrinolysis lead to experimental thrombosis augmentation.

An increase in aldosterone levels positively correlates with an increased risk of acute cardiovascular thrombotic events. The aim of the study was to determine the mechanism of action of prothrombotic aldosterone focusing on the rapid effects of the hormone on platelets, coagulation, and fibrinolysis. A wide panel of advanced ex vivo and in vitro techniques was used for the evaluation of coagulation and fibrinolysis in aldosterone-treated rats.

The myeloperoxidase product, hypochlorous acid, reduces thrombus formation under flow and attenuates clot retraction and fibrinolysis in human blood.

Hypochlorite (HOCl), a strong oxidant and antimicrobial agent, has been proposed to be associated with hemostatic abnormalities during inflammatory response. However, its complex impact on hemostasis is not completely understood. In this report we studied the effect of clinically relevant (micromolar) HOCl concentrations on thrombus formation under flow, kinetics of platelet-fibrin clot formation, its architecture, retraction, and lysis.

Effect of quinolinic acid - A uremic toxin from tryptophan metabolism - On hemostatic profile in rat and mouse thrombosis models.

Purpose: We aimed to determine the effect of quinolinic acid (QA) on hemostasis in rat and mouse models of thrombosis.

Material And Methods: Wistar rats (male, n = 72) received QA dissolved in drinking water in doses of 3, 10, 30 mg/kg or pure drinking water (vehicle control group -VEH) for 14 days. On the 14 day of the experiment the effect of QA on hemostasis was evaluated using electrically induced arterial thrombosis model.

New Sides of Aldosterone Action in Cardiovascular System as Potential Targets for Therapeutic Intervention.

Aldosterone, the main mineralocorticoid hormone, plays a crucial role in the regulation of electrolyte homeostasis and blood pressure. Although this role is undoubtedly important, it is not a hormonal action that attracts the most attention. Aldosterone seems to be very important as a local messenger in the pathology of cardiovascular diseases (CVD).

Antithrombotic Potential of Tormentil Extract in Animal Models.

species that have been investigated so far display pharmacological activity mainly due to the presence of polyphenols. Recently, it was shown that polyphenol-rich extract from rhizome of (tormentil extract) affects the metabolism of arachidonic acid and exerts both anti-inflammatory and anti-oxidant activities, suggesting a possible effect on thrombosis. Accordingly, the aim of the study was to evaluate the effect of tormentil extract on haemostasis in a rat model of thrombosis.

Angiotensin-converting enzyme inhibitors attenuate propofol-induced pro-oxidative and antifibrinolytic effect in human endothelial cells.

Introduction: The aim of this study was to investigate the effects of plasma and tissue angiotensin-converting enzyme inhibitors (ACE-Is) against propofol-induced endothelial dysfunction and to elucidate the involved mechanisms in vitro.

Materials And Methods: We examined the effects of propofol (50 μM), quinaprilat and enalaprilat (10 M) on fibrinolysis (t-PA, PAI-1, TAFI antigen levels), oxidative stress parameters (HO and MDA antigen levels and SOD and NADPH oxidase mRNA levels) and nitric oxide bioavailability (NO/NO concentration and NOS expression at the level of mRNA) in human umbilical vein endothelial cells (HUVECs).

Results: We found that both ACE-Is promoted similar endothelial fibrinolytic properties and decreased oxidative stress in vitro.

New agents modulating the renin-angiotensin-aldosterone system-Will there be a new therapeutic option?

The renin-angiotensin-aldosterone system (RAAS) is more complex than it was originally regarded. According to the current subject knowledge, there are two main axes of the RAAS: (1) angiotensin-converting enzyme (ACE)-angiotensin II-AT receptor axis and (2) ACE2-angiotensin-(1-7)-Mas receptor axis. The activation of the first axis leads to deleterious effects, including vasoconstriction, endothelial dysfunction, thrombosis, inflammation, and fibrosis; therefore, blocking the components of this axis is a highly rational and commonly used therapeutic procedure.