HDL and atherosclerosis: Insights from inherited HDL disorders

Calabresi, Laura; Gomaraschi, Monica; Simonelli, Sara; Bernini, Franco; Franceschini, Guido

doi:10.1016/j.bbalip.2014.07.015

Cited by 57 publications

(41 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…32 These findings are supported by mechanistic in vitro studies. 27,33,34 Du et al showed that small, dense HDL subfractions (i.e., HDL 3 -C) are the most efficient mediators of macrophage cholesterol efflux; they conclude that HDL-directed therapies should focus on increasing this HDL subclass.…”

Section: Discussionmentioning

confidence: 71%

High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort

et al. 2016

View full text Add to dashboard Cite

Background and Aims Recent failures of HDL cholesterol (HDL-C)-raising therapies to prevent cardiovascular disease (CVD) events have tempered the interest in the role of HDL-C in clinical risk assessment. Emerging data suggest that the atheroprotective properties of HDL depend on specific HDL particle characteristics not reflected by HDL-C. The purpose of this study was to determine the association of HDL particle concentration (HDL-P) and HDL subclasses with mortality in a high-risk cardiovascular population and to examine the clinical utility of these parameters in mortality risk discrimination and reclassification models. Methods Using nuclear magnetic resonance spectroscopy, we measured HDL-P and HDL subclasses in 3972 individuals enrolled in the CATHGEN coronary catheterization biorepository; tested for association with all-cause mortality in robust clinical models; and examined the utility of HDL subclasses in incremental mortality risk discrimination and reclassification. Results Over an average follow-up of eight years, 29.6% of the individuals died. In a multivariable model adjusted for ten CVD risk factors, HDL-P [HR, 0.71 (0.67-0.76), p= 1.3e-24] had a stronger inverse association with mortality than did HDL-C [HR 0.93 (0.87-0.99), p=0.02]. Larger HDL size conferred greater risk and the sum of medium- and small-size HDL particles (MS-HDL-P) conferred less risk. Furthermore, the strong inverse relation of HDL-P levels with mortality was accounted for entirely by MS-HDL-P; HDL-C was not associated with mortality after adjustment for MS-HDL-P. Addition of MS-HDL-P to the GRACE Risk Score significantly improved risk discrimination and risk reclassification. Conclusion HDL-P and smaller HDL subclasses were independent markers of residual mortality risk and incremental to HDL-C in a high-risk CVD population. These measures should be considered in risk stratification and future development of HDL-targeted therapies in high-risk populations.

show abstract

Section: Discussionmentioning

confidence: 71%

High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort

et al. 2016

View full text Add to dashboard Cite

show abstract

“…HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) is the primary enzyme regulating cholesterol biosynthesis [7]. During transportation, excessive hepatic cholesterol is transported into the serum via low-density lipoprotein receptor (LDLR) [8] whilst the reverse transportation depends on scavenger receptor class B type I (SR-BI) [9]. Furthermore, the conversion from cholesterol to bile acid is carried out by cholesterol-7α-hydroxylase (CYP7a1) and cholesterol-27a-hydroxylase (CYP27a1) [10].…”

Section: Introductionmentioning

confidence: 99%

Maternal Betaine Supplementation throughout Gestation and Lactation Modifies Hepatic Cholesterol Metabolic Genes in Weaning Piglets via AMPK/LXR-Mediated Pathway and Histone Modification

et al. 2016

View full text Add to dashboard Cite

Betaine serves as an animal and human nutrient which has been heavily investigated in glucose and lipid metabolic regulation, yet the underlying mechanisms are still elusive. In this study, feeding sows with betaine-supplemented diets during pregnancy and lactation increased cholesterol content and low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SR-BI) gene expression, but decreasing bile acids content and cholesterol-7a-hydroxylase (CYP7a1) expression in the liver of weaning piglets. This was associated with the significantly elevated serum betaine and methionine levels and hepatic S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) content. Concurrently, the hepatic nuclear transcription factor liver X receptor LXR was downregulated along with activated signal protein AMP-activated protein kinase (AMPK). Moreover, a chromatin immunoprecipitation assay showed lower LXR binding on CYP7a1 gene promoter and more enriched activation histone marker H3K4me3 on LDLR and SR-BI promoters. These results suggest that gestational and lactational betaine supplementation modulates hepatic gene expression involved in cholesterol metabolism via an AMPK/LXR pathway and histone modification in the weaning offspring.

show abstract

“…Furthermore, a Japanese haplotype analysis revealed that the haplotype G (rs2893880)-C (rs10740055)-G (rs7087507)-A (rs10761600) was negatively associated with susceptibility to coronary artery disease ( P = 0.049). [12] Several studies of genetic animal models have proven that increased serum HDL-C levels may protect against atherosclerosis,[192021] while other researchers have also demonstrated that low HDL-C levels are a well-defined risk factor for the development of cardiovascular diseases. [22]…”

Section: Discussionmentioning

confidence: 99%

Relationship between Modulator Recognition Factor 2/AT-rich Interaction Domain 5B Gene Variations and Type 2 Diabetes Mellitus or Lipid Metabolism in a Northern Chinese Population

Sun

Zhang

Chen

et al. 2017

Chinese Medical Journal

View full text Add to dashboard Cite

Background:Four single nucleotide polymorphisms (SNPs) in the modulator recognition factor 2/AT-rich interaction domain 5B (MRF2/ARID5B) gene located at chromosome 10q21.2 have been shown to be associated with both type 2 diabetes mellitus (T2DM) and coronary artery disease in a Japanese cohort. This study aimed to investigate the relationship between these SNPs (rs2893880, rs10740055, rs7087507, rs10761600) and new-onset T2DM and lipid metabolism in a Northern Chinese population.Methods:This was a case-control study. The rs2893880, rs10740055, rs7087507, and rs10761600 genetic variants were genotyped by SNPscan and analyzed in relation to T2DM susceptibility in 2000 individuals (999 with newly diagnosed T2DM and 1001 controls without diabetes mellitus). Associations between the MRF2/ARID5B genetic models and T2DM were determined by multivariate logistic regression.Results:Regarding the rs10740055 SNP, AA was associated with a higher risk of T2DM compared with codominant-type CC (adjusted by sex, age, and body mass index [BMI], P = 0.041, odds ratio [OR] = 1.421, 95% confidence interval [CI] 1.014–1.991). Meanwhile, AA individuals were at increased risk of presenting with T2DM compared with individuals with CC or a single C (adjusted by sex, age, and BMI, P = 0.034, OR = 1.366, 95% CI 1.023–1.824). With respect to rs10761600, AT contributed to a higher risk of T2DM compared with AA (adjusted by sex, age, and BMI, P = 0.013, OR = 1.585, 95% CI 1.101–2.282), while TT also increased the risk of presenting with T2DM compared with AA or A (adjusted by sex, age, and BMI, P = 0.004, OR = 1.632, 95% CI 1.166–2.284). High-density lipoprotein cholesterol (HDL-C) levels were significantly different among the three genotypes of rs7087507 in the controls (P = 0.048) (GG>GA).Conclusions:The present results identified MRF2/ARID5B as a potential susceptibility gene for new-onset T2DM in a Northern Chinese population, while the rs7087507 SNP was associated with HDL-C levels. Further larger studies are required to validate these findings.

show abstract

HDL and atherosclerosis: Insights from inherited HDL disorders

Cited by 57 publications

References 80 publications

High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort

High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort

Maternal Betaine Supplementation throughout Gestation and Lactation Modifies Hepatic Cholesterol Metabolic Genes in Weaning Piglets via AMPK/LXR-Mediated Pathway and Histone Modification

Relationship between Modulator Recognition Factor 2/AT-rich Interaction Domain 5B Gene Variations and Type 2 Diabetes Mellitus or Lipid Metabolism in a Northern Chinese Population

Contact Info

Product

Resources

About