Abstract：
:Hypercholesterolemia, is a prominent risk factor for cardiovascular disease (CVD). Undestanding of the biochemical mechanisms that regulate the expression of the low density lipoproteins receptor (LDLR) and the hepatic clearance of LDL cholesterol (LDL-C) paved the way to the statin therapy as the gold standard for CVD prevention. The discovery of proteins that regulate - at a post-translational level - the activity of the LDLR has been a major breakthrough in developing new cholesterol-lowering drugs. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key modulator of the LDLR degradation in the liver. Genetic studies confirmed that in humans PCSK9 mutations associate with hypercholesterolemia and hypocholesterolemia (gain-of-function or loss-of-function variants respectively). Moreover, PCSK9 is up-regulated by statin treatment and limits the efficacy of these agents. These findings led to the development of PCSK9 inhibitors. Anti-PCSK9 monoclonal antibodies showed encouraging results and are currently being evaluated in phase III clinical trials. The aim of this short review is to describe the new frontier of PCSK9 inhibition in the treatment of hypercholesterolemia. Emphasis here is given to critical emerging issues linked to PCSK9 physiology and pharmacology, which will require future investigation to definitely address the potential of anti-PCSK9 drugs in clinical practice.
journal_name
Vascul Pharmacoljournal_title
Vascular pharmacologyauthors
Norata GD,Tibolla G,Catapano ALdoi
10.1016/j.vph.2014.05.011subject
Has Abstractpub_date
2014-08-01 00:00:00pages
103-11issue
2eissn
1537-1891issn
1879-3649pii
S1537-1891(14)00107-4journal_volume
62pub_type
杂志文章,评审abstract：:The purpose of this study was to determine if P-selectin, an adhesion molecule involved in the transendothelial movement of leukocytes, might also have a direct influence on the function of cells that come into contact with it. Human peripheral blood mononuclear cells were incubated on immobilized P-selectin or a cont...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2005.11.002
更新日期：2006-03-01 00:00:00
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 ...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2016.04.006
更新日期：2016-07-01 00:00:00
abstract：BACKGROUND:Immunosuppressive agents are at the forefront of preventing organ rejection after transplantation. However, their effects on vascular smooth muscle cell-mediated intimal hyperplasia that occurs in post-transplant coronary artery disease are less well known. METHODS AND RESULTS:We investigated the in vitro e...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2004.10.002
更新日期：2004-05-01 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：:Although the vasorelaxing effects of testosterone (T) and various androgen metabolites have been observed in a variety of blood vessels and species, previous studies have not systematically compared the vasorelaxing effects of androgen metabolites in different vascular beds within the same species. Therefore, we studi...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2012.01.008
更新日期：2012-03-01 00:00:00
abstract：:The heart is subjected to chronic mechanical unloading during prolonged spaceflight and microgravity. The heart in patients with end-stage heart failure is also unloaded in prolonged duration after left ventricular assist devices (LVAD) are implanted. Heterotopic heart transplantation in rats is an established model o...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2009.10.004
更新日期：2010-03-01 00:00:00
abstract：:Endothelial cell dysfunction is considered to be an early event which subsequently leads to vascular wall disorders. Ultrastructural studies indicate that the endothelial cell changes involve membrane damage, increased permeability, swelling and necrosis. The endothelial cell loss of function could be as a result of c...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2006.11.005
更新日期：2007-04-01 00:00:00
abstract：BACKGROUND:Antitumor activity of paclitaxel is based on promotion of abnormal microtubule (MT) assembly but it is also considered to have significant pro-inflammatory and anti-angiogenic effects in vivo and thus may cause vascular dysfunction. METHODS:We studied 27 women treated with paclitaxel-containing combinations...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2010.05.002
更新日期：2010-09-01 00:00:00
abstract：:Peroxisome proliferator-activated receptors (PPAR)alpha, gamma and beta/delta belong to the nuclear receptor family of ligand-activated transcription factors. PPARs heterodimerize with the retinoid X receptor (RXR) and then act as transcription factors to modulate the function of many target genes. PPARalpha, gamma an...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2005.11.014
更新日期：2006-07-01 00:00:00
abstract：:Sixty-seven male patients with hypercholesterolemia, divided into three groups according to apolipoprotein E phenotype (33 with apoE3/ 3 phenotype, E3 group; 23 with 2/2 or 2/3, E2+ group; 11 with 4/4 or 4/3, E4+ group), received daily 20-40 mg of fluvastatin for 12 weeks. The levels of triglyceride (TG), cholesterol ...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2003.09.002
更新日期：2003-12-01 00:00:00
abstract：BACKGROUND:Tissue Factor (TF) plays a pivotal role in coronary thrombosis. Oxidized low-density lipoproteins (oxLDL) are crucial in development of atherosclerosclerosis. Moreover, oxLDL are known to induce TF expression on several cell types including endothelial cells. The lectin-type oxidized LDL receptor 1 (LOX-1) r...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2020.106822
更新日期：2020-11-21 00:00:00
abstract：:The early stages of invasion are characterized by the extracellular proteolysis and the accumulation of specialized extracellular matrix (ECM) scaffold, that are responsible for the development of vascular bed, endothelial cell proliferation and invasion of tumour cells. The ground substance of provisional matrix cons...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2006.12.004
更新日期：2007-06-01 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：: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：:Prostaglandin E2 (PGE2), a cyclooxygenase metabolite that generally acts as a systemic vasodepressor, has been shown to have vasopressor effects under certain physiologic conditions. Previous studies have demonstrated that PGE2 receptor signaling modulates angiotensin II (Ang II)-induced hypertension, but the interact...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2016.05.015
更新日期：2016-09-01 00:00:00
abstract：:Thalidomide is an antiangiogenic drug and is clinically useful in a number of cancers. However, the molecular mechanism by which thalidomide exerts its antitumor effects is poorly understood. This study was designed to clarify the relationship between antiangiogenesis and antitumor effects of thalidomide and to explor...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2005.04.003
更新日期：2005-08-01 00:00:00
abstract：:β-Adrenoceptors (β-ARs) modulate ERK1/2 and p38 in different cells, but little is known about the contribution of these signaling pathways to the function of β-ARs in vascular tissue. Immunoblotting analysis of rat aortic rings, primary endothelial (ECs) and smooth muscle cells (SMCs) isolated from aorta showed that β...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2014.04.003
更新日期：2014-05-01 00:00:00
abstract：:The antiplatelet and antithrombotic activities of a newly synthesized CP201, 2-(3,5-di-tert-butyl-4-hydroxyl)-3-chloro-1,4-naphthoquinone on human platelet aggregation in vitro and murine pulmonary thrombosis in vivo were examined. In addition, the antiplatelet activity of CP201 involved in calcium-signaling cascade w...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2004.04.001
更新日期：2004-02-01 00:00:00
abstract：BACKGROUND:Suboptimal platelet inhibition still represents an important challenge, especially for patients undergoing percutaneous coronary interventions (PCI). Chronic kidney disease (CKD) is a common comorbidity of patients with coronary artery disease, and may potentially influence platelet reactivity. So far only f...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2015.10.006
更新日期：2016-04-01 00:00:00
abstract：:Numerous studies of acetylcholine (ACh)-induced endothelium-dependent relaxation in arteries have been reported since the original description by Furchgott and Zawadzki (1980). ACh also produces endothelium-independent relaxation. However, it is still unknown whether ACh-induced AMP-activated protein kinase (AMPK) act...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2013.07.007
更新日期：2013-09-01 00:00:00
abstract：:We investigated the regulation of the epithelial sodium channel (ENaC) in human bone marrow endothelial cells (HBMEC) responding to mineralocorticoid hormones and other accessory effectors. The message for both the mineralocorticoid receptor (MCR) and the alpha subunit of ENaC was expressed in HBMEC as predicted bands...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2003.08.003
更新日期：2004-01-01 00:00:00
abstract：OBJECTIVE:Intranasal immunization with a fusion protein of the ApoB100-derived peptide p210 and the cholera toxin B subunit (CTB-p210) has previously been shown to induce mucosal tolerance and reduce atherosclerosis development, but the exact mode of action remains to be elucidated. Recent studies have indicated an imp...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2018.09.002
更新日期：2018-12-01 00:00:00
abstract：OBJECTIVE:The major objective of the present study was to examine the cardioprotective effect of resveratrol, an antioxidant presents in red wine, in the rat after ischemia-reperfusion (I/R). DESIGN:The left coronary artery was in occlusion for 30 min followed by a 120 min reperfusion in anesthetized rats. Animals wer...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2006.04.002
更新日期：2006-08-01 00:00:00
abstract：:While brain-derived neurotrophic factor (BDNF) was previously reported to induce relaxation of conduit artery, whether the BDNF/TrkB (tropomyosin-related kinase) pathway is involved in the tone control of resistance arteries is not known. This study investigated TrkB receptors levels/localization and the vasomotor eff...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2018.02.005
更新日期：2018-07-01 00:00:00
abstract：:Cardiovascular diseases are the major challenge to modern medicine. Intervention to cardiovascular cells is crucial for treatment of the diseases. Here we report a novel intervention to vascular smooth muscle (VSM) cells by optogenetics. Channelrhodopsin in a tandem with YFP was selectively expressed in smooth muscle ...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2015.03.006
更新日期：2015-08-01 00:00:00
abstract：OBJECTIVE:Inflammation and oxidative stress play a key role in the initiation, propagation, and development of atherosclerosis. Arterial baroreflex (ABR) dysfunction induced by sinoaortic denervation (SAD) promoted the development of atherosclerosis in ApoE-/- mice. The present work was designed to examine whether ABR ...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2016.08.008
更新日期：2016-12-01 00:00:00
abstract：:Chemerin is an adipokine associated with increased blood pressure, and may link obesity with hypertension. We tested the hypothesis that chemerin-induced contraction of the vasculature occurs via calcium flux in smooth muscle cells. Isometric contraction of rat aortic rings was performed in parallel with calcium kinet...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2016.11.009
更新日期：2017-01-01 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：:Obesity rates are rising in HIV-infected populations; however, the putative role of highly active antiretroviral therapy (HAART) in the development of endothelial and cardiovascular derangements in the presence of pre-existing overweight/obesity is unclear. Although dual peroxisome proliferator-activated receptors-alp...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2019.106577
更新日期：2019-10-01 00:00:00
