Acute vascular and cardiac effects of lenvatinib in mice.

Background: Tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF) receptor signalling are used in cancer therapy to inhibit angiogenesis. Unfortunately, VEGF inhibitors are known to induce severe hypertension in patients. This study aimed to elucidate the impact of the TKI lenvatinib on blood pressure, arterial stiffness, vascular reactivity, as well as cardiac function in a short-term murine model to shed light on potential contributors to cardiovascular (CV) toxicities associated with VEGF inhibition.

Lack of intracranial atherosclerosis in various atherosclerotic mouse models.

Although mice are used extensively to study atherosclerosis of different vascular beds, limited data are published on the occurrence of intracranial atherosclerosis. Since intracranial atherosclerosis is a common cause of stroke and is associated with dementia, a relevant animal model is needed to study these diseases. We examined the presence of intracranial atherosclerosis in different atherogenic mouse strains and studied differences in vessel wall characteristics in mouse and human tissue in search of possible explanations for the differing atherosclerotic susceptibility between extracranial and intracranial vessels.

The MAASWERP Study: An International, Comparative Case Study on Measuring Biomechanics of the Aged Murine Aorta.

Introduction: Arterial stiffening is a hallmark of vascular ageing, and unravelling its underlying mechanisms has become a central theme in the field of cardiovascular disease. While various techniques and experimental setups are accessible for investigating biomechanics of blood vessels both in vivo and ex vivo, comparing findings across diverse methodologies is challenging.

Methods: Arterial stiffness in the aorta of adult (5 months) and aged (24 months) wild-type C57Bl/6J mice was measured in vivo, after which ex vivo biomechanical evaluation was performed using the Rodent Oscillatory Tension Setup to study Arterial Compliance (ROTSAC; University of Antwerp, Belgium) and the DynamX setup (Maastricht University, The Netherlands).

Short-Term Proteasome Inhibition: Assessment of the Effects of Carfilzomib and Bortezomib on Cardiac Function, Arterial Stiffness, and Vascular Reactivity.

Proteasome inhibitors such as bortezomib and carfilzomib induce apoptosis and are a cornerstone in the treatment of relapsed or refractory multiple myeloma. However, concerns have emerged concerning their link to cancer therapy-related cardiovascular dysfunction (CTRCD). Bortezomib, a reversible first-generation inhibitor, and carfilzomib, a second-generation irreversible inhibitor, are associated with hypertension, heart failure, and cardiac arrhythmias.

Dexrazoxane prevents vascular toxicity in doxorubicin-treated mice.

Background: Doxorubicin (DOX) is used for breast cancer and lymphoma, but can cause cardiotoxicity, arterial stiffness, and endothelial dysfunction. We recently reported SERPINA3N as biomarker of cardiovascular toxicity in patients and mice. Dexrazoxane (DEXRA) is an FDA-approved drug that prevents DOX-induced cardiac toxicity in high-risk patients.

Calciprotein particles induce arterial stiffening ex vivo and impair vascular cell function.

Calciprotein particles (CPPs) are an endogenous buffering system, clearing excessive amounts of Ca and PO from the circulation and thereby preventing ectopic mineralization. CPPs circulate as primary CPPs (CPP1), which are small spherical colloidal particles, and can aggregate to form large, crystalline, secondary CPPs (CPP2). Even though it has been reported that CPPs are toxic to vascular smooth muscle cells (VSMC) in vitro, their effect(s) on the vasculature remain unclear.

Use of the BRANT-MERQS scoring table for the quality assessment of type 3 medication review in patients with rheumatoid arthritis and those with type 2 diabetes mellitus.

Background: A type 3 medication review (MR3) is a patient-centred medication service primarily provided by pharmacists and is presently employed routinely in several countries. In this process, pharmacists interview patients and collaborate with the treating physician to optimize the patient's pharmacotherapy, taking into account the patient's medication history and other medical data including laboratory values. The need to maintain the quality of such interventions during and after their initial implementation cannot be overstated.

Unravelling the impact of active and passive contributors to arterial stiffness in male mice and their role in vascular aging.

Arterial stiffness, a key indicator of vascular health, encompassing active (vascular tone) and passive (extracellular matrix) components. This study aims to address how these different components affect arterial stiffness along the aorta and the influence of aging. Aortic segments of 12 week and 24 month old (both n = 6) male C57BL/6J mice were mounted in a Rodent Oscillatory Set-up to study Arterial Compliance, in order to measure arterial stiffness and vascular reactivity.

Characterization of systolic and diastolic function, alongside proteomic profiling, in doxorubicin-induced cardiovascular toxicity in mice.

Background: The anthracycline doxorubicin (DOX) is a highly effective anticancer agent, especially in breast cancer and lymphoma. However, DOX can cause cancer therapy-related cardiovascular toxicity (CTR-CVT) in patients during treatment and in survivors. Current diagnostic criteria for CTR-CVT focus mainly on left ventricular systolic dysfunction, but a certain level of damage is required before it can be detected.

Design and Synthesis of 1,3-Diarylpyrazoles and Investigation of Their Cytotoxicity and Antiparasitic Profile.

Herein, we report a series of 1,3-diarylpyrazoles that are analogues of compound /HIT 8. We previously identified this molecule as a 'hit' during a high-throughput screening campaign for autophagy inducers. A variety of synthetic strategies were utilized to modify the 1,3-diarylpyrazole core at its 1-, 3-, and 4-position.

GPX4 overexpression does not alter atherosclerotic plaque development in ApoE knock-out mice.

Ferroptosis is a type of regulated necrosis that is associated with iron-dependent accumulation of lipid hydroperoxides. Given that iron deposition and lipid peroxidation initiate ferroptosis in atherosclerosis and contribute to further plaque development, we hypothesized that inhibition of ferroptosis could be of value in the treatment of atherosclerosis. Glutathione peroxidase 4 (GPX4) is the only enzyme known capable of reducing lipid hydroperoxides.

α-Tocopherol inhibits atherogenesis and improves cardiac function in mice independently of its antioxidant properties.

The impact of α-tocopherol on atherosclerosis is unclear and controversial. While some studies suggest potential benefits, such as antioxidant properties that may reduce oxidative stress, other studies indicate no significant preventive effects. The intricate interplay of various factors, including dosage, individual differences, and study methodologies, contributes to the ongoing uncertainty surrounding α-tocopherol's role in atherosclerosis.

Medication Review: What's in a Name and What Is It about?

Background: Medication review is a multifaceted service aimed at optimizing the use of medicines and enhancing the health outcomes of patients. Due to its complexity, it is crucial to clearly describe the service, its variants, and its components to avoid confusion and ensure a better understanding of medication review among healthcare providers.

Aim: This study aims to bring clarity to the origins, definitions, abbreviations, and types of medication reviews, together with the primary criteria that delineate key features of this service.

Programmed death of macrophages in atherosclerosis: mechanisms and therapeutic targets.

Atherosclerosis is a progressive inflammatory disorder of the arterial vessel wall characterized by substantial infiltration of macrophages, which exert both favourable and detrimental functions. Early in atherogenesis, macrophages can clear cytotoxic lipoproteins and dead cells, preventing cytotoxicity. Efferocytosis - the efficient clearance of dead cells by macrophages - is crucial for preventing secondary necrosis and stimulating the release of anti-inflammatory cytokines.

Dexrazoxane does not mitigate early vascular toxicity induced by doxorubicin in mice.

Apart from cardiotoxicity, the chemotherapeutic agent doxorubicin (DOX) provokes acute and long-term vascular toxicity. Dexrazoxane (DEXRA) is an effective drug for treatment of DOX-induced cardiotoxicity, yet it remains currently unknown whether DEXRA prevents vascular toxicity associated with DOX. Accordingly, the present study aimed to evaluate the protective potential of DEXRA against DOX-related vascular toxicity in a previously-established in vivo and ex vivo model of vascular dysfunction induced by 16 hour (h) DOX exposure.

Pharmacological modulation of vascular ageing: A review from VascAgeNet.

Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets.

Key elements in the quality assessment of a type 3 medication review.

Medication reviews are a structured evaluation of a patient's pharmacotherapy with the aim of optimizing medicines use and improving health outcomes. This entails detecting drug related problems and recommending interventions. A high level of quality is essential for the successful implementation of this service in community pharmacies but currently there is no instrument or tool to assess that overall quality.

The effect of cyclic stretch on aortic viscoelasticity and the putative role of smooth muscle focal adhesion.

Due to its viscoelastic properties, the aorta aids in dampening blood pressure pulsatility. At the level of resistance-arteries, the pulsatile flow will be transformed into a continuous flow to allow for optimal perfusion of end organs such as the kidneys and the brain. In this study, we investigated the viscoelastic properties of different regions of the aorta of healthy C57Bl6/J adult mice as well as the interplay between (altered) cyclic stretch and viscoelasticity.

Doxorubicin-induced cardiovascular toxicity: a longitudinal evaluation of functional and molecular markers.

Aims: Apart from cardiotoxicity, the chemotherapeutic doxorubicin (DOX) induces vascular toxicity, represented by arterial stiffness and endothelial dysfunction. Both parameters are of interest for cardiovascular risk stratification as they are independent predictors of future cardiovascular events in the general population. However, the time course of DOX-induced cardiovascular toxicity remains unclear.

Empagliflozin decreases ageing-associated arterial stiffening and vascular fibrosis under normoglycemic conditions.

Arterial stiffness is a hallmark of vascular ageing and results in increased blood flow pulsatility to the periphery, damaging end-organs such as the heart, kidneys and brain. Treating or "reversing" arterial stiffness has therefore become a central target in the field of vascular ageing. SGLT2 inhibitors, initially developed in the context of type 2 diabetes mellitus, have become a cornerstone of heart failure treatment.

Optimization of bioanalysis of dried blood samples.

Introduction: Pharmacokinetic/pharmacodynamic modelling has emerged as a valuable technique for understanding drug exposure and response relationships in drug development. Pharmacokinetic data are often obtained by taking multiple blood samples, which may disturb physiological parameters and complicate study designs. Wearable automatic blood sampling systems can improve this limitation by collecting dried blood samples at programmable time points without disrupting cardiovascular parameters.

Effect of erythrophagocytosis-induced ferroptosis during angiogenesis in atherosclerotic plaques.

Intraplaque (IP) angiogenesis is a key feature of advanced atherosclerotic plaques. Because IP vessels are fragile and leaky, erythrocytes are released and phagocytosed by macrophages (erythrophagocytosis), which leads to high intracellular iron content, lipid peroxidation and cell death. In vitro experiments showed that erythrophagocytosis by macrophages induced non-canonical ferroptosis, an emerging type of regulated necrosis that may contribute to plaque destabilization.

The impact of environmental and biological factors on the resting heart rate of dogs as assessed using 20 years of data from safety pharmacology studies.

Introduction: A safety pharmacology study detects and evaluates potential side effects of a new drug on physiological function at therapeutic levels and above and, in most cases, prior to the initiation of clinical trials. The aim of this study was to investigate the effects of environmental and biological factors on resting heart rate (HR), a representative cardiac parameter in cardiovascular safety pharmacology.

Methods: Over twenty years, 143 dogs (Beagles, Labradors and mongrels) received implanted telemetry transmitters to measure aortic pressure (AP), left ventricular pressure (LVP), Electrocardiogram (ECG) and body temperature.

Patient experiences and opinions on medication review: a qualitative study.

Background: Medication reviews are a structured critical evaluation of a patient's pharmacotherapy, carried out by a healthcare professional, but are not yet a routine pharmaceutical service in Belgium. A pilot project to initiate an advanced medication review (= type 3 medication review) in community pharmacies was set up by the Royal Pharmacists' Association of Antwerp.

Aim: To investigate the experiences and opinions of patients who participated in this pilot project.

Optimization of the Solvent and In Vivo Administration Route of Auranofin in a Syngeneic Non-Small Cell Lung Cancer and Glioblastoma Mouse Model.

The antineoplastic activity of the thioredoxin reductase 1 (TrxR) inhibitor, auranofin (AF), has already been investigated in various cancer mouse models as a single drug, or in combination with other molecules. However, there are inconsistencies in the literature on the solvent, dose and administration route of AF treatment in vivo. Therefore, we investigated the solvent and administration route of AF in a syngeneic SB28 glioblastoma (GBM) C57BL/6J and a 344SQ non-small cell lung cancer 129S2/SvPasCrl (129) mouse model.