Abstract:
:Familial hypercholesterolemia (FH) is a genetic autosomal dominant disorder caused by an impaired receptor-mediated low-density lipoprotein (LDL) removal from the circulation, mainly due to disruptive autosomal co-dominant mutations in the LDL receptor (LDLr) gene, but also less frequently in the apolipoprotein B100 (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. A rare form of autosomal recessive FH has been also described due to LDLr adaptor protein 1 (LDLRAP1) gene mutations. FH is characterized by very high levels of plasma LDL cholesterol associated with the high incidence of premature atherosclerotic cardiovascular disease (CVD). Despite heterozygous FH (HeFH) patients are still poorly recognized and treated, there is today a large availability of drugs (i.e., statins, ezetimibe and PCSK9 inhibitors) allowing theoretically the normalization of plasma LDL cholesterol levels in this population. Homozygous FH patients (HoFH) have a more severe form of FH, characterized by low responsiveness to the conventional lipid-lowering treatment and often associated with unfavorable prognosis in the young age. Inspired by promising outcomes obtained by orthotopic liver transplantation (OLT), scientists are investigating the possibility of correcting the defective LDLr in these patients by using gene therapy approaches to achieve a novel therapeutic solution with high efficiency. In this article, we tried to review the in vitro, ex vivo, and in vivo attempts conducted to correct FH-causing LDLr gene mutations by using different methods of gene delivery, gene editing, and stem cell manipulation. We also discussed some clinical trials performed in this context.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Hajighasemi S,Mahdavi Gorabi A,Bianconi V,Pirro M,Banach M,Ahmadi Tafti H,Reiner Ž,Sahebkar Adoi
10.1016/j.phrs.2019.03.016subject
Has Abstractpub_date
2019-05-01 00:00:00pages
119-132eissn
1043-6618issn
1096-1186pii
S1043-6618(18)31913-3journal_volume
143pub_type
杂志文章,评审abstract::The effect of age and sex on the predictive value of colorectal cancer (CRC) patients treated with immune checkpoint inhibitors (ICIs) has been controversial, and the effect of specific gene mutations on the predictive value of CRC patients treated with ICIs remains to be explored. Our study analyzed the influence of ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.105028
更新日期:2020-09-01 00:00:00
abstract::The blood-brain barrier (BBB) keeps the central nervous system (CNS) safe from various brain diseases, while the BBB makes it difficult for effective drugs to enter the CNS. Mfsd2a is specifically expressed on the cell membrane of brain-microvascular endothelial cell (BMEC) and is implicated in the delivery of some su...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2015.12.024
更新日期:2016-02-01 00:00:00
abstract::This study was performed in order to investigate the cholinomimetic response of seminal vesicles isolated from rats treated with hydrocortisone acetate during perinatal life. At the adult phase, the body weight and the wet weight of the seminal vesicle of these animals were unchanged. However, these male rats exhibite...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:
更新日期:2003-07-01 00:00:00
abstract::The interaction of mianserin with ethanol in central nervous system (CNS) was investigated. Mianserin was administered at a single dose of 5 or 20 mgkg(-1) i.p. or as daily injections in a dose of 2.5 mgkg(-1) given for 14 days. The influence of mianserin on acute ethanol toxicity (LD(50)), on ED(50) of ethanol in rot...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/s1043-6618(02)00031-2
更新日期:2002-07-01 00:00:00
abstract::Heart rate slowing has been accepted for decades as a primary therapeutic approach to prevention (and even to treatment) of angina pectoris. Pure heart rate slowing has not been achieved with previously available rate-slowing pharmacological agents (beta adrenergic blockers, certain calcium channel blockers), all of w...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2006.03.017
更新日期:2006-05-01 00:00:00
abstract::Skeletal muscle fitness is vital for human health and disease and is determined by the capacity for burning fuel, mitochondrial ATP production, and contraction. High quality mitochondria in skeletal muscle are essential for maintaining energy homeostasis in response to a myriad of physiologic or pathophysiological str...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2018.12.020
更新日期:2019-03-01 00:00:00
abstract::Alzheimer's is the neurodegenerative disease affecting the largest number of patients in the world. In spite of the intense research of the last decades, progress about its knowledge and therapy was limited. In particular, various cytotoxic processes remained debated, while the few drugs approved for therapy were of o...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2019.104316
更新日期:2019-08-01 00:00:00
abstract::A growing number of evidences from clinical and preclinical studies have shown that dysregulation of microRNA (miRNA) function contributes to the progression of cancer and thus miRNA can be an effective target in therapy. Dietary phytochemicals, such as quercetin, are natural products that have potential anti-cancer p...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2019.104346
更新日期:2019-09-01 00:00:00
abstract::Mesial temporal lobe epilepsy (MTLE) is frequently associated with hippocampal sclerosis (Hs), possibly caused by a primary brain injury that occurs a long time before the appearance of neurological symptoms. MTLE-Hs is, however, a heterogeneous condition that evolves with time, involving both environmental and geneti...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2016.09.019
更新日期:2016-11-01 00:00:00
abstract::Several studies have demonstrated that any beneficial effects of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), of which simvastatin (Merck Sharp & Dohme) is an example, on coronary events are linked to their hypocholesterolemic properties. The in vivo effects of simvastatin treatment ...
journal_title:Pharmacological research
pub_type: 临床试验,杂志文章
doi:10.1006/phrs.2000.0787
更新日期:2001-04-01 00:00:00
abstract::Short-chain fatty acids (SCFAs), mainly including acetate, propionate, and butyrate, are metabolites produced during the bacterial fermentation of dietary fiber in the intestinal tract. They are believed to be essential factors affecting host health. Most in vitro and ex vivo studies have shown that SCFAs affect the r...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2021.105420
更新日期:2021-01-09 00:00:00
abstract::The growing size of trials on primary and secondary prevention of acute coronary syndromes characterised by very broad inclusion criteria may seem logical to 'trialists', who reason that the the broader the inclusion criteria, the easier it is to recruit large numbers of patients in a short period of time and the more...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1006/phrs.1998.0316
更新日期:1998-06-01 00:00:00
abstract::By the use of combined radioreceptor binding and autoradiographic techniques we attempted to analyse the biochemical characteristics and the anatomical localization of GABA-B receptors in sections of rat circle of Willis and pialarachnoid arteries. 3H-GABA in the presence of 40 microM isoguvacine and 2.5 mM CaCl2 was ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/1043-6618(90)90731-r
更新日期:1990-05-01 00:00:00
abstract::Metastatic cancers account for more than 90% of cancer mortality. The metastasis of all cancers is critically mediated by enzymes that degrade extracellular matrix. Aggressive tumors are characterized by an imbalance between enzymes that degrade ECM and endogenous inhibitors of the enzymes. Matrix metalloproteinases (...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2010.11.003
更新日期:2011-02-01 00:00:00
abstract::The intestinal barrier function depends on an adequate response to pathogens by the epithelium. Toll-like receptor 3 (TLR-3) recognizes double-stranded RNA, a virus-associated molecular pattern. Activation of TLR-3 with Poly(I:C), a synthetic agonist, modulates tissue repair and permeability in other epithelia; howeve...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2015.06.016
更新日期:2015-11-01 00:00:00
abstract::The effect of the inhalation of vaporized ethanol on injected [1-14C]pyruvate kinetics was studied in mice. The [1-14C]pyruvate kinetics were modelled by means of a four-compartment closed model, i.e. injected site, blood, periphery and expired 14CO2. The results show that the inhalation of vaporized ethanol can stimu...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1997.0261
更新日期:1998-01-01 00:00:00
abstract::The purpose of the present work was to study the change in morphine metabolic ratio in obese subjects before and after Roux-en-Y Gastric Bypass (RYGB) and to identify clinical and/or biological factors associated with this change. The pharmacokinetics (PK) of oral morphine (30mg), morphine-3-glucuronide (M3G) and morp...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.08.031
更新日期:2017-04-01 00:00:00
abstract::Posttranslational modifications of proteins are important regulatory processes endowing the proteins functional complexity. Over the last decade, numerous studies have shed light on the roles of palmitoylation, one of the most common lipid modifications, in various aspects of neuronal functions. Major players regulati...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2016.06.008
更新日期:2016-09-01 00:00:00
abstract::In China, child and adolescent pediatricians often face challenges in treating children with the appropriate medications. Within the last 8 years, the Chinese government has already initiated a series of policies to promote development of age-appropriate medicines for children. In this study,we introduced the current ...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2019.104412
更新日期:2019-10-01 00:00:00
abstract::Using cultured human keratinocytes, the present study investigates the role of nitric oxide (NO) in the mediation of the antiproliferative effects of ultraviolet light A (UVA). UVA treatment of cells (3-21 J cm (-2)) caused a time- and dose-dependent increase in nitrite formation in a micromolar range. This effect was...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2001.0939
更新日期:2002-03-01 00:00:00
abstract::The antipsychotic drug olanzapine is widely used in the treatment of schizophrenia, bipolar and other mental disorders; however, it causes serious metabolic disorders, including dyslipidemia. Our previous studies have identified that olanzapine activated expression of the sterol regulatory element binding transcriptio...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.104703
更新日期:2020-05-01 00:00:00
abstract::(+)-3-(3-Hydroxyphenyl)-N-(1-propyl)-piperidine (3-PPP; a sigma receptor ligand), administered at 30 mg kg-1, 30 min before the test, significantly decreased the electroconvulsive threshold in mice, being ineffective in lower doses. 3-PPP (20 mg kg-1) diminished the protective activity of diphenylhydantoin, phenobarbi...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1999.0548
更新日期:1999-12-01 00:00:00
abstract::Endocannabinoids are part of a bioactive lipid signaling system, not only in the central nervous system but also in various peripheral organs. Accumulating evidence implicates dysregulation of the endocannabinoid system (ECS) in the pathogenesis of various cardiovascular diseases, including hypertension, atheroscleros...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2009.04.003
更新日期:2009-08-01 00:00:00
abstract::Herpesviruses encode transmembrane G protein-coupled receptors (GPCRs), which share structural homology to human chemokine receptors. These viral GPCRs include KSHV-encoded ORF74, EBV-encoded BILF1, and HCMV-encoded US28, UL33, UL78 and US27. Viral GPCRs hijack various signaling pathways and cellular networks, includi...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2020.104804
更新日期:2020-06-01 00:00:00
abstract::Severely obese patients undergoing bariatric surgery (BS) are at increased risk for venous thromboembolism (VTE). How standard low molecular weight heparin (LMWH) regimen should be adapted to provide both sufficient efficacy and safety in this setting is unclear. We aimed to compare the influence of four body size des...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2018.02.012
更新日期:2018-05-01 00:00:00
abstract::Segetoside I is a plant-derived bisdesmosidic saponin from Vaccaria segetalis (Neck) with reported anticancer activities. This development has raised an interest in the therapeutic potential of segetoside I. Here, we report the in vitro and in vivo antitumor activities of segetoside I against some selected cancer cell...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.04.032
更新日期:2016-08-01 00:00:00
abstract::An important aspect of brain cholinesterase function is related to enzymatic differences. The brain of mammals contains two major forms of cholinesterases: acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The two forms differ genetically, structurally and for their kinetics. Butyrylcholine is not a physi...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2003.11.017
更新日期:2004-10-01 00:00:00
abstract::Curcumin, a bioactive polyphenol, is a yellow pigment of the Curcuma longa (turmeric) plant. Curcumin has many pharmacologic effects including antioxidant, anti-carcinogenic, anti-obesity, anti-angiogenic and anti-inflammatory properties. Recently, it has been found that curcumin affects lipid metabolism, and subseque...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2017.02.008
更新日期:2017-05-01 00:00:00
abstract::MicroRNAs (miRNAs) are short single-stranded RNAs that have pivotal roles in disease pathophysiology through transcriptional and translational modulation of important genes. It has been implicated in the development of many diseases, such as stroke, cardiovascular conditions, cancers and inflammatory airway diseases. ...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2020.105045
更新日期:2020-10-01 00:00:00
abstract::This paper describes a new sensitive gas chromatographic method with electron capture detector to assay estazolam in human plasma, which has been developed and validated for pharmacokinetic purposes. The drug and the internal standard (triazolam) were extracted from plasma buffered at pH 9.0 into toluene and analysed ...
journal_title:Pharmacological research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1006/phrs.1997.0144
更新日期:1997-04-01 00:00:00