Pieter-Jan Guns

Pieter-Jan Guns
University of Antwerp | UA · Physiopharmacology Research Group

PhD, Pharm. D.

About

69
Publications
4,207
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858
Citations
Introduction
Pieter-Jan Guns currently is Assistant Professor in the research group of Physiopharmacology at the University of Antwerp. Research interest include cardiovascular safety pharmaoclogy, arterial stiffness and atherosclerosis.
Education
September 2003 - October 2007
University of Antwerp
Field of study
  • Pharmaceutical Sciences
October 1998 - July 2003
University of Antwerp
Field of study
  • Pharmaceutical Sciences

Publications

Publications (69)
Article
Cardiac arrhythmias are associated with cardiovascular morbidity and mortality. Cardiac electrophysiology studies (EPS) use intracardiac catheter recording and stimulation for profound evaluation of the heart's electrical properties. The main clinical application is investigation and treatment of rhythm disorders. These techniques have been transla...
Article
Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Research Foundation - Flanders (Brussels, BE): ==> [DUTCH]: "Fonds voor Wetenschappelijk Onderzoek (FWO) - Vlaanderen" Introduction The pulsatile character of blood flow in the central arteries results in a local transmission of energy to the arterial wall, actin...
Article
Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders Introduction Myocarditis is an inflammatory disease of the heart with viral infections being the most common aetiology. Often, myocardial fibrosis (MF) is observed during the resolution of myocarditis. MF i...
Article
Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Fonds voor Wetenschappelijk Onderzoek (FWO) Introduction Necroptosis is a form of regulated necrosis mediated by the kinase activity of receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and executed by RIPK3 and mixed lineage kinase domain like pseud...
Article
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Gasdermin D (GSDMD) is the key executor of pyroptotic cell death. Recent studies suggest that GSDMD-mediated pyroptosis is involved in atherosclerotic plaque destabilization. We report that cleaved GSDMD is expressed in macrophage- and smooth muscle cell-rich areas of human plaques. To determine the effects of GSDMD deficiency on atherogenesis, Apo...
Article
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RIPK1 (receptor-interacting serine/threonine-protein kinase 1) enzymatic activity drives both apoptosis and necroptosis, a regulated form of necrosis. Because necroptosis is involved in necrotic core development in atherosclerotic plaques, we investigated the effects of a RIPK1S25D/S25D mutation, which prevents activation of RIPK1 kinase, on athero...
Poster
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There are signifcant differences in viscoelastic properties between segments from distinct anatomical regions along the aortic tree, especially when comparing thoracic and abdominal aortic tissue. Pulsatile load (either via pulse frequency or via pulse pressure) modulates the viscoelastic properties of the arterial wall due to, in part, strain rate...
Article
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Vein grafting is a frequently used surgical intervention for cardiac revascularization. However, vein grafts display regions with intraplaque (IP) angiogenesis, which promotes atherogenesis and formation of unstable plaques. Graft neovessels are mainly composed of endothelial cells (ECs) that largely depend on glycolysis for migration and prolifera...
Chapter
Cardiovascular disease continues to be the leading cause of death worldwide, which drives the urgent need for novel therapies. Autophagy has been found to play an essential role in maintaining a healthy vasculature. In different vascular pathologies such as atherosclerosis, medial vascular calcification, arterial stiffness, and hypertension, autoph...
Article
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Clinical and animal studies have demonstrated that chemotherapeutic doxorubicin (DOX) increases arterial stiffness, a predictor of cardiovascular risk. Despite consensus about DOX-impaired endothelium-dependent vasodilation as a contributing mechanism, some studies have reported conflicting results on vascular smooth muscle cell (VSMC) function aft...
Article
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Measuring arterial stiffness has recently gained a lot of interest because it is a strong predictor for cardiovascular events and all-cause mortality. However, assessing blood vessel stiffness is not easy and the in vivo measurements currently used provide only limited information. Ex vivo experiments allow for a more thorough investigation of (alt...
Article
Radiotherapy in cancer treatment involves the use of ionizing radiation for cancer cell killing. Although radiotherapy has shown significant improvements on cancer recurrence and mortality, several radiation-induced adverse effects have been documented. Of these adverse effects, radiation-induced cardiovascular disease (CVD) is particularly promine...
Article
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Increasing epidemiological evidence highlights the association between systemic insulin resistance and Alzheimer’s disease (AD). As insulin resistance can be caused by high-stress hormone levels and since hypercortisolism appears to be an important risk factor of AD, we aimed to investigate the systemic insulin functionality and circulating stress...
Article
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Myocarditis is an inflammatory disease of the heart with viral infections being the most common aetiology. Its complex biology remains poorly understood and its clinical management is one of the most challenging in the field of cardiology. Toll-like receptors (TLRs), a family of evolutionarily conserved pattern recognition receptors, are increasing...
Article
Endothelial cells (ECs) secrete different paracrine signals that modulate the function of adjacent cells; two examples of these paracrine signals are nitric oxide (NO) and neuregulin-1 (NRG1), a cardioprotective growth factor. Currently, it is undetermined whether one paracrine factor can compensate for the loss of another. Herein, we hypothesized...
Article
Importin 8, encoded by IPO8, is a ubiquitously expressed member of the importin-β protein family that translocates cargo molecules such as proteins, RNAs, and ribonucleoprotein complexes into the nucleus in a RanGTP-dependent manner. Current knowledge of the cargoes of importin 8 is limited, but TGF-β signaling components such as SMAD1–4 have been...
Article
Arterial stiffness is an important predictor of cardiovascular risk. Clinical studies have demonstrated that arterial stiffness increases in cancer patients treated with the chemotherapeutic doxorubicin (DOX). However, the mechanisms of DOX-induced arterial stiffness remain largely unknown. This study aimed to evaluate artery stiffening in DOX-trea...
Article
Full-text available
Radiotherapy in cancer treatment involves the use of ionizing radiation for cancer cell killing. Although radiotherapy has shown significant improvements on cancer recurrence and mortality, several radiation-induced adverse effects have been documented. Of these adverse effects, radiation-induced cardiovascular disease (CVD) is particularly promine...
Article
Background: Toll-like receptors (TLRs) are a family of transmembrane pattern recognition receptors that are mainly expressed on immune cells. Recognition of various exogenous and endogenous molecular patterns activates the TLR signalling cascade, which orchestrates an inflammatory immune response. Dysfunctional immune responses, including aberrant...
Article
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Background: Autophagy is a highly conserved catabolic homeostatic process, crucial for cell survival. It has been shown that autophagy can modulate different cardiovascular pathologies, including vascular calcification (VCN). Objective: To assess how modulation of autophagy, either through induction or inhibition, affects vascular and valvular c...
Article
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Safety pharmacology is an essential part of drug development aiming to identify, evaluate and investigate undesirable pharmacodynamic properties of a drug primarily prior to clinical trials. In particular, cardiovascular adverse drug reactions (ADR) have halted many drug development programs. Safety pharmacology has successfully implemented a scree...
Article
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MRI diffusion data suffers from significant inter-and intra-site variability, which hinders multi-site and/or longitudinal diffusion studies. This variability may arise from a range of factors, such as hardware, reconstruction algorithms and acquisition settings. To allow a reliable comparison and joint analysis of diffusion data across sites and o...
Article
Objective Intraplaque neovascularization is an important feature of unstable human atherosclerotic plaques. However, its impact on plaque formation and stability is poorly studied. Because proliferating endothelial cells generate up to 85% of their ATP from glycolysis, we investigated whether pharmacological inhibition of glycolytic flux by the sma...
Article
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The Sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) actively pumps Ca2+ into the sarco/endoplasmic reticulum, thereby regulating intracellular Ca2+ concentrations and associated physiological processes. Different SERCA isoforms have been described (SERCA1, 2, and 3) with SERCA2 playing a pivotal role in Ca2+ homeostasis in cardiovascular tissues....
Article
Background Decreased eNOS activity is the hallmark of endothelial dysfunction and is associated with cardiovascular and renal disorders. Besides NO, endothelial cells produce numerous other small molecules, peptides, and proteins, which modulate the function of adjacent cells. For instance, neuregulin-1 (NRG-1) is an endothelium-derived growth fact...
Article
Aims: Cardiovascular ageing is a key determinant of life expectancy. Cellular senescence, a state of irreversible cell cycle arrest, is an important contributor to ageing due to the accumulation of damaged cells. Targeting cellular senescence could prevent age-related cardiovascular diseases. In this study, we investigated the effects of neureguli...
Article
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Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly population. In this study, we used the APP/PS1 transgenic mouse model to explore the feasibility of using diffusion kurtosis imaging (DKI) as a tool for the early detection of microstructural changes in the brain du...
Article
Background: Amyloid-related imaging abnormalities (ARIA) have been reported with some anti-amyloid-β (Aβ) immunotherapy trials. They are detected with magnetic resonance imaging (MRI) and thought to represent transient accumulation of fluid/edema (ARIA-E) or microhemorrhages (ARIA-H). Although the clinical significance and pathophysiology are unkn...
Article
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While no definitive cure for Alzheimer's disease exists yet, currently available treatments would benefit greatly from an earlier diagnosis. It has previously been shown that Magnetization Transfer Contrast (MTC) imaging is able to detect amyloid β plaques in old APP/PS1 mice. In the current study we investigated if MTC is also able to visualize ea...
Article
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Introduction: The cholinergic system is involved in learning and memory and is affected in neurodegenerative disorders such as Alzheimer's disease. The possibility of non-invasively detecting alterations of neurotransmitter systems in the mouse brain would greatly improve early diagnosis and treatment strategies. The hypothesis of this study is th...
Article
Amyloid deposition in the brain is considered an initial event in the progression of Alzheimer's disease. We hypothesized that the presence of amyloid plaques in the brain of APP/presenilin 1 mice leads to higher diffusion kurtosis measures due to increased microstructural complexity. As such, our purpose was to provide an in vivo proof of principl...
Article
Introduction: Evaluation of drug-related effects on cardiovascular function is part of the core battery described in the ICH S7A guideline. Anesthetized guinea-pigs are excellent models for the evaluation of drug-induced prolongation of ventricular repolarization; however less information is available regarding other cardio-hemodynamic parameters...
Article
Introduction: Assessment of the propensity of novel drugs to cause proarrhythmia is essential in the drug development process. It is increasingly recognized, however, that QT prolongation alone is an imperfect surrogate marker for Torsades de Pointes (TdP) arrhythmia prediction. In the present study we investigated the behavior of a novel surrogat...
Article
QT prolongation is commonly used as a surrogate marker for Torsade de Pointes (TdP) risk of non-cardiovascular drugs. However, use of this indirect marker often leads to misinterpretation of the realistic TdP risk, as tested compounds may cause QT prolongation without evoking TdP in humans. A negative electro-mechanical (E-M) window has recently be...
Article
Recent evidence suggests that amyloid precursor protein (APP) is overexpressed in atherosclerosis-prone regions of mouse aorta. We therefore investigated in the present study whether APP has a role in the progression and composition of atherosclerotic plaques. Apolipoprotein E-deficient (apoE(-/-)) mice were crossbred with animals lacking APP (APP(...
Article
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Site-specific atherosclerosis is generally attributed to differential gene expression in endothelial cells. We investigated whether the transcriptome of smooth muscle cells is different between atherosclerosis-prone and atherosclerosis-resistant regions in apolipoprotein E-deficient (apoE-/-) mice before plaque development, and in C57Bl/6 mice. De-...
Article
P2Y nucleotide receptors are involved in the regulation of vascular tone, smooth muscle cell (SMC) proliferation and inflammatory responses. The present study investigated whether they are involved in atherosclerosis. mRNA of P2Y receptors was quantified (RT-PCR) in atherosclerotic and plaque-free aorta segments of apolipoprotein E-deficient (apoE(...
Article
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P2Y receptors are G-protein-coupled receptors activated by extracellular nucleotides. The P2Y(6) receptor is selectively activated by UDP, and its transcript has been detected in numerous organs, including the spleen, thymus, intestine, blood leukocytes, and aorta. To investigate the biological functions of this receptor, we generated P2Y(6)-null m...
Article
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Transgenesis of human paraoxonase 1 (PON1), a HDL-associated enzyme that destroys lipid peroxides, has been reported to reduce early atherogenesis in mice. The present study explored the therapeutic potential of human PON1 gene transfer in old apolipoprotein E-deficient (apoE(-/-)) mice with advanced atherosclerosis. ApoE(-/-) mice (18 months, regu...
Article
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Acetylcholine (ACh)-induced relaxation declines in apolipoprotein E-deficient (apoE-/-) mouse aortas, but only after atherosclerotic plaque formation. This study investigated intracellular calcium concentrations [Ca2+]i and changes in phenylephrine-induced contractions as index of baseline nitric oxide (NO) bioavailability before plaque development...
Article
To study the effect of hypercholesterolemia on vascular smooth muscle cell (VSMC) function, atherosclerosis-prone but plaque-free endothelium-denuded aortic rings (width 2mm) from C57Bl6 Wild Type (WT) and apolipoprotein E-deficient (apoE(-/-)) mice (age 4 months) were mounted in a myograph and loaded with Fura-2 AM to simultaneously measure free C...
Article
Based on pharmacological criteria, we previously suggested that in the mouse aorta endothelium-dependent relaxation by nucleotides is mediated by P2Y1 (ADP), P2Y2 (ATP) and P2Y6 (UDP) receptors. For UTP it was unclear whether P2Y2, P2Y6 or yet another subtype was involved. Therefore, in view of the lack of selective purinergic agonists and antagoni...
Article
The present study investigated whether the higher contractile behaviour of apoE-/- compared with wild type (wt) C57Bl/6J aortic segments is due to an increased contractile status of the smooth muscle cells or a lower basal relaxant effect of the endothelium. Endothelium-intact or -denuded aortic strips or rings were mounted in a myograph and loaded...
Article
The present study investigated whether lesion-free aorta segments of young apoE-/- mice, which will later show endothelial dysfunction when atherosclerotic lesions develop, display normal endothelial function in comparison with ‘wild-type’ (wt) C57Bl/6J mice. Endothelial function was assessed by studying endothelium-dependent relaxation to acetylch...
Article
Based on pharmacological criteria, we previously suggested that in the mouse aorta, endothelium-dependent relaxation by nucleotides is mediated by P2Y1 (adenosine diphosphate (ADP)), P2Y2 (adenosine triphosphate (ATP)) and P2Y6 (uridine diphosphate (UDP)) receptors. For UTP, it was unclear whether P2Y2, P2Y6 or yet another subtype was involved. The...
Article
Nucleotides regulate various effects including vascular tone. This study was aimed to characterize P2Y receptors on endothelial cells of the aorta of C57BL6 mice. Five adjacent segments (width 2 mm) of the thoracic aorta were mounted in organ baths to measure isometric force development. Nucleotides evoked complete (adenosine 5′ triphosphate (ATP),...
Article
Previously we reported that the acetylcholine-induced relaxation in the isolated aorta of apolipoprotein E-deficient (apoE-/-) mice deteriorates after the development of atherosclerotic plaques, but remains normal in adjacent, plaque-free segments. The present study investigated the presence of functional purinergic receptors in the murine aorta, a...

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