Abstract:
PURPOSE OF REVIEW:Homozygous familial hypercholesterolemia (HoFH) is a rare disorder associated with early atherosclerotic disease due to impairment of the LDL receptor (LDLR) pathway. Because of their molecular defect, current treatment options have limited success in bringing HoFH patient to LDL-C target and morbidity and mortality remain high. We review current and upcoming therapies directed at HoFH, including gene therapy. RECENT FINDINGS:Recent real-world studies have confirmed the strength in lomitapide as a treatment adjunct to statins and other lipid-lowering therapies in HoFH patients. The approval of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor monoclonal antibodies has also been a welcome addition to the treatment armamentarium offering an additional average reduction in LDL-C levels of 24% when added to background lipid-lowering therapies in this population. Although achieving adequate LDL-C levels in this population is difficult, there are several therapies on the horizon that may help more patients reach goal. Evinacumab, a monoclonal antibody against ANGPTL3, has been shown to substantially reduce LDL-C of an average of 49%, independently of residual LDLR activity. RNA interference targeting PCSK9 and ANGPTL3 shows promise in clinical trials. Adeno-associated virus-mediated gene transfer and gene editing techniques are in early clinical and preclinical development. SUMMARY:LDL-C lowering in HoFH patients remains very challenging. However, novel treatment options are emerging. Upcoming therapies directed at PCSK9 and ANPTL3 may offer additional LDL-C reduction, to help patients achieve adequate LDL-C levels. Gene therapy and gene editing techniques, if proven effective, may offer a unique opportunity to treat patients with a one-time treatment.
journal_name
Curr Opin Lipidoljournal_title
Current opinion in lipidologyauthors
Bajaj A,Cuchel Mdoi
10.1097/MOL.0000000000000677subject
Has Abstractpub_date
2020-06-01 00:00:00pages
119-124issue
3eissn
0957-9672issn
1473-6535journal_volume
31pub_type
杂志文章abstract:PURPOSE OF REVIEW:Mesenchymal stem cells (or multipotent stromal cells) are emerging as a potent cell type for cardiac cell therapy. This review describes the potential of cardiac mesenchymal stem cell therapy, but also highlights some recently discovered less favorable mesenchymal stem cell characteristics. RECENT FI...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e3282f0dd1f
更新日期:2007-12-01 00:00:00
abstract:PURPOSE OF REVIEW:This review provides an overview of newly described mechanisms by which peroxisome proliferator-activated receptors (PPARs) (α, γ, and δ) regulate several factors associated with cardiovascular risk. RECENT FINDINGS:PPAR agonists have known effects on plasma lipoprotein levels, inflammation, and insu...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e3283613a7d
更新日期:2013-06-01 00:00:00
abstract:PURPOSE OF REVIEW:The antioxidant activity of high-density lipoprotein is largely due to the paraoxonase 1 located on it. Experiments with transgenic paraoxonase 1 knock-out mice indicate the potential for this enzyme to protect against atherogenesis. This effect of high-density lipoprotein in decreasing low-density li...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-200208000-00002
更新日期:2002-08-01 00:00:00
abstract:PURPOSE OF REVIEW:To provide an update on clinical trials of gene therapy for atherosclerotic cardiovascular disease published since 1 August 2001 and summarize the general advantages and potential problems of gene transfer in these disorders. RECENT FINDINGS:There are two major areas in which gene therapy has entered...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-200212000-00009
更新日期:2002-12-01 00:00:00
abstract::A site-specific cytidine deamination (cytidine to uridine) in nuclear apolipoprotein B messenger RNA creates a translational stop codon that produces apolipoprotein B48. This process is mediated by an enzyme composed of distinct subunits, including apolipoprotein B messenger RNA editing enzyme catalytic polypeptide-1 ...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-199504000-00002
更新日期:1995-04-01 00:00:00
abstract:PURPOSE OF REVIEW:Epidemiological and clinical studies link low levels of HDL cholesterol (HDL-C) with increased risk of atherosclerotic cardiovascular disease (CVD). However, genetic polymorphisms linked to HDL-C do not associate consistently with CVD risk, and randomized clinical studies of drugs that elevate HDL-C v...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000446
更新日期:2017-10-01 00:00:00
abstract::Expression profiling and genomic DNA sequence comparisons are increasingly being applied to the identification and analysis of the genes that are involved in lipid metabolism. Not only has genome-wide expression profiling aided in the identification of novel genes that are involved in important processes in lipid meta...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-200204000-00009
更新日期:2002-04-01 00:00:00
abstract:PURPOSE OF REVIEW:Phospholipids are major constituents in the intestinal lumen after meal consumption. This article highlights current literature suggesting the contributory role of intestinal phospholipid metabolism toward cardiometabolic disease manifestation. RECENT FINDINGS:Group 1b phospholipase A2 (PLA2g1b) cata...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000334
更新日期:2016-10-01 00:00:00
abstract:PURPOSE OF REVIEW:Control of vascular smooth muscle cell (VSMC) phenotype is essential in the development and maintenance of a healthy vasculature. Acquisition of a synthetic, proproliferative phenotype by VSMCs following vascular insult is central to neointimal formation and the development of vascular pathology. Micr...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e32835719a1
更新日期:2012-10-01 00:00:00
abstract:PURPOSE OF REVIEW:Sortilin, encoded SORT1 gene at chromosome 1p13.3, is a multiligand receptor that traffics protein from the Golgi to the endosomes, secretory vesicles, and the cell surface. Genome-wide association studies (GWAS) revealed an association between sortilin and reduced plasma LDL-cholesterol (LDL-C) as we...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000598
更新日期:2019-06-01 00:00:00
abstract:PURPOSE OF REVIEW:The effects of hormone-replacement therapy on cardiovascular risk factors are examined. In an attempt to explain the results of recent randomized controlled trials in which no benefit of hormone-replacement therapy for postmenopausal women has been observed, RECENT FINDINGS:Changes in lipoproteins in...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/01.mol.0000137231.84772.80
更新日期:2004-08-01 00:00:00
abstract:PURPOSE OF REVIEW:Regulation of cholesterol homeostasis is a complex interplay of a multitude of metabolic pathways situated in different organs. The liver plays a central role and has received most attention of the research community. In this review, we discuss recent progress in the understanding of the emerging role...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e3283395e45
更新日期:2010-06-01 00:00:00
abstract:PURPOSE OF REVIEW:Despite their pathophysiological importance, the molecular mechanisms and enzymatic components of lipid mobilization from intracellular storage compartments are insufficiently understood. The aim of this review is to evaluate the role of hormone-sensitive lipase in this process. RECENT FINDINGS:Hormo...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-200306000-00009
更新日期:2003-06-01 00:00:00
abstract:PURPOSE OF REVIEW:The cell death-inducing DFF45-like effector (CIDE) family proteins, comprising three members, Cidea, Cideb, and Fsp27 (Cidec), have emerged as important regulators for various aspects of metabolism. This review summarizes our current understanding about the physiological roles of CIDE proteins, their ...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e328328d0bb
更新日期:2009-04-01 00:00:00
abstract:PURPOSE OF REVIEW:Endocannabinoids are defined as endogenous agonists of cannabinoid receptors, that is, of the two G-protein-coupled receptors for the Cannabis psychoactive principle Delta-tetra-hydrocannabinol. Two such endogenous mediators have been most thoroughly studied so far: anandamide and 2-arachidonoylglycer...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e32803dbdec
更新日期:2007-04-01 00:00:00
abstract::Atherosclerotic macrovascular disease is the leading cause of both morbidity and mortality in non-insulin dependent diabetes mellitus. Endothelial dysfunction is a key, early and potentially reversible event in pathogenesis of atherosclerosis. Its occurrence in non-insulin dependent diabetes mellitus is well supported...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-199910000-00002
更新日期:1999-10-01 00:00:00
abstract:PURPOSE OF REVIEW:To discuss crucial cues (chemokines, adhesion molecules and pharmacological means) that guide and control the context-specific mobilization, recruitment and fate of circulating progenitor cells in arterial repair and plaque stability. RECENT FINDINGS:The mobilization and recruitment of bone marrow de...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e32830dfe33
更新日期:2008-10-01 00:00:00
abstract::The inhibiting effect of insulin on the mobilization of free fatty acids (FFA) from adipose tissue is halted in prevalent conditions with systemic insulin resistance. The nature and cause of this perturbation are unknown, but steroid hormones may be involved. The consequence is the creation or amplification of insulin...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-199405030-00003
更新日期:1994-06-01 00:00:00
abstract:PURPOSE OF REVIEW:Studies have shown the three-member paraoxonase (PON) multigene family to be involved in the development of a large variety of diseases with an inflammatory component. Environmental factors such as lifestyle-related factors differ widely between populations and it is important to consider that their i...
journal_title:Current opinion in lipidology
pub_type: 杂志文章
doi:10.1097/MOL.0000000000000687
更新日期:2020-08-01 00:00:00
abstract::Apolipoprotein E has key functions in lipoprotein metabolism, and polymorphisms in the apolipoprotein E gene are associated with distinct lipoprotein patterns. The possibility of gene-nutrient interactions for apolipoprotein E has been addressed in many studies. Although results have generally been mixed, the indicati...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-200202000-00005
更新日期:2002-02-01 00:00:00
abstract:PURPOSE OF REVIEW:This review addresses how, in atherosclerosis or systemic inflammation, HDL can lose its usual atheroprotective characteristics and even paradoxically assume proinflammatory properties. RECENT FINDINGS:Specific chemical and structural changes within HDL particles can impede reverse cholesterol transp...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e3282364a17
更新日期:2007-08-01 00:00:00
abstract:PURPOSE OF REVIEW:Use of suitable animal models is essential for investigation of the mechanisms underlying cardiac events and development of the therapeutic strategies; however, ideal animal models that can recapitulate human coronary atherosclerosis and subsequent acute myocardial infarction are still lacking. In thi...
journal_title:Current opinion in lipidology
pub_type: 社论,评审
doi:10.1097/MOL.0b013e3283189c18
更新日期:2008-12-01 00:00:00
abstract:PURPOSE OF REVIEW:This review highlights the recent key advances in our understanding of the role of phospholipid transfer protein in lipid and lipoprotein metabolism. RECENT FINDINGS:The overexpression of human phospholipid transfer protein in mice is associated with an increase in atherosclerosis. This is consistent...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-200406000-00004
更新日期:2004-06-01 00:00:00
abstract:PURPOSE OF REVIEW:Proprotein convertase subtilisin kexin type 9 (PCSK9) acts as an endogenous natural inhibitor of the LDL receptor pathway, by targeting the receptor to lysosomes for degradation. Beside the liver, PCSK9 is also expressed at significant levels in other tissues, where its function remains unclear. The c...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000180
更新日期:2015-06-01 00:00:00
abstract:PURPOSE OF REVIEW:It is increasingly recognized that profound metabolic changes occur in activated myeloid cells, which shape their inflammatory phenotype and cellular functions. The purpose of this review is to summarize the accumulating evidence that major metabolic adaptations occur in monocytes and macrophages in t...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000539
更新日期:2018-10-01 00:00:00
abstract:PURPOSE OF REVIEW:The goal of this review is to provide an update on the most recent and relevant findings in the area of genotype-phenotype associations as well as the relationships between genetic factors and cardiovascular disease risk markers and events. In addition, emphasis will be placed on the methodological pr...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/01.mol.0000217895.67444.de
更新日期:2006-04-01 00:00:00
abstract:PURPOSE OF REVIEW:Substantial risk of ASCVD events persists despite intensive statin therapy and other agents to lower LDL-C. The optimal way to address other elements of dyslipidemia, such as triglyceride-rich particles (TRL) and when to treat has remained unclear. RECENT FINDINGS:Several lines of evidence indicate t...
journal_title:Current opinion in lipidology
pub_type: 杂志文章
doi:10.1097/MOL.0000000000000694
更新日期:2020-08-01 00:00:00
abstract:PURPOSE OF REVIEW:Inflammation has been widely acknowledged to contribute throughout all stages of atherogenesis. However, these recent advances in our understanding have not been translated into clinical practice in which the mainstay of treatment is still lipid-targeted therapy. This review provides an overview of pr...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e3283587543
更新日期:2012-12-01 00:00:00
abstract:PURPOSE OF REVIEW:To review the recent studies on intensive glucose control and the risk of cardiovascular disease (CVD) in type 2 diabetes, to discuss potential reasons for discordant results among recent trials, and to comment on implications for clinical practice. RECENT FINDINGS:Three large randomized controlled t...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e328332dfaa
更新日期:2010-02-01 00:00:00
abstract:PURPOSE OF REVIEW:The endoplasmic reticulum (ER) maintains cellular metabolic homeostasis by coordinating protein synthesis, secretion activities, lipid biosynthesis and calcium (Ca²⁺) storage. In this review, we will discuss how altered ER homeostasis contributes to dysregulation of hepatic lipid metabolism and contri...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000056
更新日期:2014-04-01 00:00:00