Abstract：
BACKGROUND:Macrophages play a central role in atherosclerosis development and progression, hence, targeting macrophage activity is considered an attractive therapeutic. Recently, we documented nanomedicinal delivery of the anti-inflammatory compound prednisolone to atherosclerotic plaque macrophages in patients, which did however not translate into therapeutic efficacy. This unanticipated finding calls for in-depth screening of drugs intended for targeting plaque macrophages. METHODS AND RESULTS:We evaluated the effect of several candidate drugs on macrophage activity, rating overall performance with respect to changes in cytokine release, oxidative stress, lipid handling, endoplasmic reticulum (ER) stress, and proliferation of macrophages. Using this in vitro approach, we observed that the anti-inflammatory effect of prednisolone was counterbalanced by multiple adverse effects on other key pathways. Conversely, pterostilbene, T0901317 and simvastatin had an overall anti-atherogenic effect on multiple pathways, suggesting their potential for liposomal delivery. CONCLUSION:This dedicated assay setup provides a framework for high-throughput assessment. Further in vivo studies are warranted to determine the predictive value of this macrophage-based screening approach and its potential value in nanomedicinal drug development for cardiovascular patients.
journal_name
Vascul Pharmacoljournal_title
Vascular pharmacologyauthors
Alaarg A,Zheng KH,van der Valk FM,da Silva AE,Versloot M,van Ufford LC,Schulte DM,Storm G,Metselaar JM,Stroes ES,Hamers AAdoi
10.1016/j.vph.2016.04.006subject
Has Abstractpub_date
2016-07-01 00:00:00pages
51-9eissn
1537-1891issn
1879-3649pii
S1537-1891(15)30007-0journal_volume
82pub_type
杂志文章abstract：:Bemiparin is a low molecular weight heparin (LMWH) indicated for the acute treatment of deep vein thrombosis with or without pulmonary embolism, for the prophylaxis of venous thromboembolism in surgical and non-surgical patients and for the prevention of clotting in the extracorporeal circuit during hemodialysis. Due ...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2014.03.001
更新日期：2014-07-01 00:00:00
abstract：:Arterial hypertension is a condition associated with endothelial dysfunction, accompanied by an imbalance in the production of reactive oxygen species (ROS) and NO. The aim of this study was to investigate and elucidate the possible mechanisms of sildenafil, a selective phosphodiesterase-5 inhibitor, actions on endoth...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2019.106601
更新日期：2020-01-01 00:00:00
abstract：:We have studied the therapeutic efficacy of the sodium alginate in experimental immune complex glomerulonephritis. Bovine serum albumin (BSA) nephritis was induced in rats by a subcutaneous immunization and daily intravenous administration of BSA. Sodium alginate at two different doses (25 and 50 mg/kg) was administer...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2005.03.002
更新日期：2005-06-01 00:00:00
abstract：BACKGROUND AND AIM:The aim of this study was to investigate the effect of acute hypercapnia due to the mechanical hypoventilation on the oxidative metabolism of peripheral blood neutrophils in the rabbit. METHODS:The study was performed on 24 Chinchilla rabbits, randomized into normo- and hypercapnia groups (P(a)CO(2)...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/s1537-1891(02)00338-5
更新日期：2003-02-01 00:00:00
abstract：:Recent studies evidence that peroxynitrite is spontaneously formed when nitric oxide (NO) and superoxide coexist and suggest that it is likely to be involved in the destruction of the pancreatic beta cells. We examined whether drugs that inhibit nitric oxide synthase (NOS) or scavenge peroxynitrite could abrogate STZ-...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/s1537-1891(02)00212-4
更新日期：2002-03-01 00:00:00
abstract：:Ion channels control electrical excitability in living cells. In mammalian heart, the opposing actions of Na(+) and Ca(2+) ion influx, and K(+) ion efflux, through cardiac ion channels determine the morphology and duration of action potentials in cardiac myocytes, thus controlling the heartbeat. The last decade has se...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2005.07.013
更新日期：2006-02-01 00:00:00
abstract：:Stem cells possess the ability of self-renewal and give rise to specific cell types. The differentiation of stem cells involves environmental factors, transduction of extra and intra-cellular signals, regulation of gene expression by transcriptional factors, microRNAs and chromosome structural modifiers. Vascular SMCs...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2012.02.014
更新日期：2012-05-01 00:00:00
abstract：BACKGROUND:Vascular calcification (VC) is associated with the high morbidity and mortality of cardiovascular diseases in dialysis patients and is a process in which vascular smooth muscle cells (VSMCs) actively differentiate into osteoblast-like cells. Reticulocalbin-2 (RCN2) is involved in the process of osteogenic di...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2020.106821
更新日期：2021-02-01 00:00:00
abstract：:We characterized vascular reactivity to endothelin-1 (ET-1) in mesenteric vessels from DOCA-salt hypertensive and SHAM control mice and assessed the effect that endothelial-derived vasodilators have on ET-1-induced vasoconstriction. Changes in the diameter of unpressurized small mesenteric arteries and veins (100- to ...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2005.02.014
更新日期：2005-06-01 00:00:00
abstract：:To investigate the vasorelaxant effect of fasudil mesylate (FM) in vivo and in vitro. The relaxation effect of FM was studied using cerebral vasospasm (CVS) model in vivo and isolated aortic rings in vitro. FM (0.35, 1.2, 3.5 mg·kg⁻¹) increased cerebrovascular flow (CVF) and femoral blood flow (FBF) dose-dependently i...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2011.06.005
更新日期：2011-11-01 00:00:00
abstract：:The present study investigates the potential of ozagrel, a thromboxane A2 (TXA2) synthase inhibitor, in bilateral common carotid artery occlusion (BCCAo) induced vascular dementia (VaD). Wistar rats were subjected to BCCAo procedure under anesthesia to induce VaD. Morris water maze (MWM) test was employed on 7th day p...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2020.106827
更新日期：2020-12-17 00:00:00
abstract：:Preclinical and clinical studies have suggested that specific subsets of cells isolated from the bone marrow or peripheral blood, collectively named endothelial progenitor cells (EPCs), play an essential role in neovascularization and are biomarkers of atherosclerosis, inversely related to the presence and progression...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2015.02.018
更新日期：2015-04-01 00:00:00
abstract：:We recently demonstrated that lipoic acid suppresses endotoxin-stimulated expression of inducible nitric oxide synthase and nitric oxide production in mouse macrophages. In this study, we tested whether lipoic acid suppresses these inflammatory mediators in the lungs of rats. Rats were assigned to receive either no sp...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2005.08.005
更新日期：2005-12-01 00:00:00
abstract：RATIONALE:We examined the role of Jak2 kinase phosphorylation in the development of pressure overload hypertrophy in mice subjected to transverse aortic constriction (TAC) and treated with tyrphostin AG490, a pharmacological inhibitor of Jak2. METHODS:Control mice (sham), subjected to TAC for 15 days (TAC) or to TAC a...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2006.05.006
更新日期：2006-12-01 00:00:00
abstract：:Our previous studies in heterozygous Ren-2 transgenic rats (TGR) have shown that early treatment with selective endothelin (ET)(A) receptor blockade is superior to nonselective ET(A/B) receptor blockade. The aim of this study was to evaluate the role of the ET system in male heterozygous TGR with established hypertens...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2008.01.009
更新日期：2008-04-01 00:00:00
abstract：:Propionyl-l-carnitine (PLC) is a natural short-chain derivative of l-carnitine (LC), a natural amino acid that plays an important role in fatty acid metabolism. Recent studies suggest that PLC has vascular protective effects. Because of the importance of endothelial nitric oxide synthase (eNOS) and its product, antiat...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2013.07.001
更新日期：2013-09-01 00:00:00
abstract：:Successful drug delivery to the central nervous system (CNS) is highly dependent on DMPK as well as physicochemical properties and it is therefore important to characterise these properties and take them into account when designing chemical lead series that act at CNS targets. Since the drug discovery/development proc...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/s1537-1891(02)00203-3
更新日期：2002-06-01 00:00:00
abstract：:Autoimmune rheumatic diseases are characterised by systemic inflammation and complex immunopathology, with an increased risk of cardiovascular disease, initiated by endothelial dysfunction in a chronic inflammatory environment. Endothelial microparticles (EMPs) are released into the circulation from activated endothel...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2016.05.016
更新日期：2016-11-01 00:00:00
abstract：:Alterations in the retinal microvessel (RMV) compartment occurring in systemic disease states such as diabetes may eventually contribute to blindness. To specifically address the pathophysiological role of the microvasculature we developed a new method for RMV bulk isolation from individual rats. The extraction proced...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2018.07.001
更新日期：2018-11-01 00:00:00
abstract：:MicroRNAs (e.g., miRNAs), endogenously expressed small non-coding RNAs, control gene expression by regulating target messenger RNA at post-transcriptional level. Recent studies have identified a specific role for microRNAs as key regulators of vascular function and dysfunction. The zebrafish (Danio rerio) system is a ...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2011.08.224
更新日期：2011-10-01 00:00:00
abstract：:Cardiac muscle extends into mammalian pulmonary veins for variable distances according to species. This study has addressed the autonomic control of electrically paced cardiac muscle of the pulmonary vein of the rat. Contractile responses of Wistar rat pulmonary veins were investigated under isometric conditions in vi...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2006.09.005
更新日期：2007-03-01 00:00:00
abstract：:Norepinephrine (NE) responses are larger in renal and femoral veins compared to phenylephrine (PE). These differences may be due to the subtypes of adrenoceptor involved in these responses or to the involvement of local modulatory mechanisms. Therefore, the present study investigated in organ bath the adrenoceptor sub...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2015.06.017
更新日期：2015-09-01 00:00:00
abstract：OBJECTIVE:In patients with familial combined hyperlipidemia (FCHL), without metabolic syndrome (MS), occurrence of non-alcoholic fatty liver disease (NAFLD) is related to a specific pro-inflammatory profile, influenced by genetic traits, involved in oxidative stress and adipokine secretion. Among FCHL or MS patients, h...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2015.04.004
更新日期：2015-09-01 00:00:00
abstract：:A small amount of adipose tissue associated with small arteries and arterioles is encountered both in mice and man. This perivascular adipose tissue (PVAT) has a paracrine effect on the vascular tone regulation. PVAT is expanded in obesity and in diabetes. This expansion not only involves enlargement of fat cells, but...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2012.02.003
更新日期：2012-05-01 00:00:00
abstract：:Nitric oxide (NO) donors are commonly used for the prevention and treatment of ischemic heart disease. Besides their effects on the heart, NO donors may also prevent hypoxic brain damage and exert beneficial effects on atherosclerosis by favoring features of plaque stability. We recently described that apolipoprotein ...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2019.05.001
更新日期：2019-01-01 00:00:00
abstract：:Activation of ATP-sensitive K+ channels (K ATP) during ischemia leads to arrhythmias and blockade of these channels exert antiarrhythmic action. In this study, we investigated the effects of HMR1098, a sarcolemmal K ATP channel blocker and 5-hydroxydeconoate (5-HD), a mitochondrial K ATP channel blocker on cardiac fun...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2005.11.006
更新日期：2006-04-01 00:00:00
abstract：OBJECTIVES:This study examined the role of Na+/K+-ATPase in the vasodilator actions of nitric oxide (NO), S-nitrosothiols and the endothelium-dependent agonist, acetylcholine. METHODS:The vasodilator responses elicited by intravenous injections of (i) the NO-donors, sodium nitroprusside and MAHMA NONOate, (ii) the S-n...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2006.06.008
更新日期：2006-12-01 00:00:00
abstract：:The sulfur-containing amino acid, taurine, has been shown to ameliorate the vascular disorders. We examined the effects of taurine ingestion on intimal thickening following balloon injury. Balloon injury was induced in the left common carotid artery of Wistar rats. Taurine (3% (w/v)) was mixed in the drinking water fr...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2010.07.003
更新日期：2010-09-01 00:00:00
abstract：:Potassium channel dysfunction plays a role in the pathogenesis of a number of vascular diseases including pulmonary and systemic hypertension, diabetes, and complications of atherosclerosis. Two types of K+ channels that are known to be prevalent and contribute significantly to the repolarization of vascular smooth mu...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s1537-1891(02)00121-0
更新日期：2002-01-01 00:00:00
abstract：:tert-Butyl hydroperoxide (t-BOOH), a membrane permeant oxidant, elicits enhanced vasoconstriction of perfused kidney and mesenteric arterial beds isolated from DOCA-salt-induced hypertensive rats. We hypothesize that enhanced vasoconstriction to t-BOOH during DOCA-salt hypertension involves free radical species and de...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/s1537-1891(02)00309-9
更新日期：2003-01-01 00:00:00
