Genetics-driven discovery of novel regulators of lipid metabolism
Purpose of review
Residual cardiovascular disease risk and increasing metabolic syndrome risk underscores a need for novel therapeutics targeting lipid metabolism in humans. Unbiased human genetic screens have proven powerful in identifying novel genomic loci, and this review discusses recent developments in such discovery.
Recent findings
Recent human genome-wide association studies have been completed in incredibly large, detailed cohorts, allowing for the identification of more than 300 genomic loci that participate in the regulation of plasma lipid metabolism. However, the discovery of these loci has greatly outpa...
Source: Current Opinion in Lipidology - May 2, 2019 Category: Lipidology Tags: LIPID METABOLISM: Edited by Marit Westerterp and Bart van de Sluis Source Type: research
Editorial introductions
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - May 2, 2019 Category: Lipidology Tags: EDITORIAL INTRODUCTIONS Source Type: research
Targeting proprotein convertase subtilisin/kexin type 9 in mice and monkeys
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - March 7, 2019 Category: Lipidology Tags: BIMONTHLY UPDATE: Edited by Alan Rees Source Type: research
Endoscopic bariatric treatments: new toolkit in the armamentarium against obesity
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - March 7, 2019 Category: Lipidology Tags: BIMONTHLY UPDATE: Edited by Alan Rees Source Type: research
Genomics of familial hypercholesterolaemia
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - March 7, 2019 Category: Lipidology Tags: BIMONTHLY UPDATE: Edited by Alan Rees Source Type: research
Cannabis effects on lipoproteins
Purpose of review
The endocannabinoid system affects several physiological functions. A family of endocannabinoid receptors is susceptible to cannabis constituents. Cannabis is widely used in our society and following its recent legalization in Canada, we focus on how exposure to cannabis and pharmacologic cannabinoid receptor type 1 (CB1) inhibition affect lipoprotein levels.
Recent findings
Several groups have reported that exposure to cannabis does not increase weight despite the marked increase in caloric intake. In observational studies, the effect of smoked cannabis exposure on plasma lipids is variable. Some st...
Source: Current Opinion in Lipidology - March 7, 2019 Category: Lipidology Tags: GENETICS AND MOLECULAR BIOLOGY: Edited by Robert A. Hegele Source Type: research
Chylomicron retention disease: genetics, biochemistry, and clinical spectrum
Purpose of review
Chylomicron retention disease (CRD) is an autosomic recessive disorder, in which intestinal fat malabsorption is the main cause of diverse severe manifestations. The specific molecular defect was identified in 2003 and consists of mutations in the SAR1B or SARA2 gene encoding for intracellular SAR1B GTPase protein. The aim of this review is first to provide an update of the recent biochemical, genetic and clinical findings, and second to discuss novel mechanisms related to hallmark symptoms.
Recent findings
CRD patients present with SAR1B mutations, which disable the formation of coat protein complex...
Source: Current Opinion in Lipidology - March 7, 2019 Category: Lipidology Tags: GENETICS AND MOLECULAR BIOLOGY: Edited by Robert A. Hegele Source Type: research
Unaccounted risk of cardiovascular disease: the role of the microbiome in lipid metabolism
Purpose of review
Not all of the risk of cardiovascular disease can be explained by diet and genetics, and the human microbiome, which lies at the interface of these two factors, may help explain some of the unaccounted risk. This review examines some of the well established links between the microbiome and cardiovascular health, and proposes relatively unexplored associations.
Recent findings
Byproducts of microbial metabolism are associated with health and disease: Trimethylamine N oxide is associated with atherosclerosis; whereas short-chain fatty acids are associated with decreased inflammation and increased energ...
Source: Current Opinion in Lipidology - March 7, 2019 Category: Lipidology Tags: GENETICS AND MOLECULAR BIOLOGY: Edited by Robert A. Hegele Source Type: research
Pathways of smooth muscle foam cell formation in atherosclerosis
Purpose of review
Smooth muscle cells (SMCs) are the major cell type in human atherosclerosis-prone arteries and take up excess lipids, thereby contributing to luminal occlusion. Here we provide a focused review on pathways by which smooth muscle cells (SMCs) can become foam cells in atherosclerosis.
Recent findings
A synthesis of recent and older investigations provides key mechanistic insights into SMC foam cell formation. LDL and other apoB-containing lipoproteins are modified by a diverse array of oxidative, enzymatic, and nonenzymatic processes present in the arterial intima. These modifications of LDL all promot...
Source: Current Opinion in Lipidology - March 7, 2019 Category: Lipidology Tags: GENETICS AND MOLECULAR BIOLOGY: Edited by Robert A. Hegele Source Type: research
Molecular regulation of plasma lipid levels during systemic inflammation and sepsis
Purpose of review
Sepsis is a common syndrome of multiorgan system dysfunction caused by a dysregulated inflammatory response to an infection and is associated with high rates of mortality. Plasma lipid and lipoprotein levels and composition change profoundly during sepsis and have emerged as both biomarkers and potential therapeutic targets for this condition. The purpose of this article is to review recent progress in the understanding of the molecular regulation of lipid metabolism during sepsis.
Recent findings
Patients who experience greater declines in high-density lipoprotein during sepsis are at much greater r...
Source: Current Opinion in Lipidology - March 7, 2019 Category: Lipidology Tags: GENETICS AND MOLECULAR BIOLOGY: Edited by Robert A. Hegele Source Type: research
From HDL-cholesterol to HDL-function: cholesterol efflux capacity determinants
Purpose of review
The validity of HDL-cholesterol (HDL-C) elevation as a therapeutic target has been questioned, in comparison to enhancing HDL functionality. Cholesterol efflux capacity (CEC) is an in-vitro assay that measures the ability of an individual's HDL to promote cholesterol efflux from cholesterol donor cells such as macrophages. CEC of HDL is a predictor of cardiovascular risk independent of HDL-C levels. However, molecular determinants of CEC and the effects of diseases and therapeutic interventions on CEC have not been completely defined.
Recent findings
We review here recent findings on elevated HDL-C a...
Source: Current Opinion in Lipidology - March 7, 2019 Category: Lipidology Tags: GENETICS AND MOLECULAR BIOLOGY: Edited by Robert A. Hegele Source Type: research
Current status of familial hypercholesterolemia in Chinese populations
Purpose of review
Heterozygous familial hypercholesterolemia often went unrecognized in China when population cholesterol levels were low, but rapid economic development has changed the situation. This review will discuss the current position of awareness, diagnosis, and management of familial hypercholesterolemia in Chinese populations.
Recent findings
The phenotype of familial hypercholesterolemia in China and other Chinese populations has become similar to that in Western countries, although it may still be somewhat less severe. The prevalence in Chinese populations is also similar to that in other countries and it...
Source: Current Opinion in Lipidology - March 7, 2019 Category: Lipidology Tags: GENETICS AND MOLECULAR BIOLOGY: Edited by Robert A. Hegele Source Type: research
Recently reported familial hypercholesterolemia-related mutations from cases in the Middle East and North Africa region
Purpose of review
Familial hypercholesterolemia is an inherited disorder where cases have a significantly higher risk of having premature myocardial infarction than noncases. The prevalence of this genetic disease is currently unknown in countries of the Middle East and North Africa region. Given that a high percentage of marriages are consanguineous in this region, the prevalence may be much higher than assumed. We systematically reviewed the literature to identify case-related mutations reported within the last 4 years and since our first report in 2014.
Recent findings
Mutations were reported in familial hyperchole...
Source: Current Opinion in Lipidology - March 7, 2019 Category: Lipidology Tags: GENETICS AND MOLECULAR BIOLOGY: Edited by Robert A. Hegele Source Type: research
Subclinical coronary atherosclerosis and cardiovascular risk stratification in heterozygous familial hypercholesterolemia patients undergoing statin treatment
Purpose of review
To discuss the heterogeneity of atherosclerotic cardiovascular disease (ASCVD) risk in heterozygous familial hypercholesterolemia and evidence and limitations of clinical risk scores and subclinical coronary atherosclerosis (SCA) imaging to evaluate risk.
Recent findings
Risk evaluation in contemporary familial hypercholesterolemia cohorts needs to consider the cause of the familial hypercholesterolemia phenotype, for example the presence of autosomal molecular defects that impart a greater ASCVD risk than in polygenic hypercholesterolemia, prospective follow-up and the impact of statin treatment. As...
Source: Current Opinion in Lipidology - March 7, 2019 Category: Lipidology Tags: GENETICS AND MOLECULAR BIOLOGY: Edited by Robert A. Hegele Source Type: research
The evolution of genetic-based risk scores for lipids and cardiovascular disease
Purpose of review
With improved next-generation sequencing technology, open-access genetic databases and increased awareness of complex trait genetics, we are entering a new era of risk assessment in which genetic-based risk scores (GRSs) will play a clinical role. We review the concepts underlying polygenic models of disease susceptibility and challenges in clinical implementation.
Recent findings
Polygenic risk scores are currently used in genetic research on dyslipidemias and cardiovascular disease (CVD). Although the underlying principles for constructing polygenic scores for lipids are established, the lack of co...
Source: Current Opinion in Lipidology - March 7, 2019 Category: Lipidology Tags: GENETICS AND MOLECULAR BIOLOGY: Edited by Robert A. Hegele Source Type: research
