Mechanistic roles of lipoprotein lipase and sphingomyelinase in low density lipoprotein aggregation

Walters, Michael J.; Wrenn, Steven P.

doi:10.1016/j.jcis.2011.07.072

Cited by 12 publications

(8 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…11,45 Acute generation of ceramide by sphingomyelinases is able to induce lipoproteins aggregation. 46 Ceramide is also implicated in oxidized LDL transcytosis across endothelial cells, thus being implicated in the retention of bioactive lipids in the vascular wall. 47 Last, endogenous ceramides regulate monocyte adhesion to vessel walls and then promotes atheroma plaque development.…”

Section: Discussionmentioning

confidence: 99%

Untargeted Lipidomics Reveals a Specific Enrichment in Plasmalogens in Epicardial Adipose Tissue and a Specific Signature in Coronary Artery Disease

Barchuk

Dutour

Ancel

et al. 2020

ATVB

View full text Add to dashboard Cite

OBJECTIVE: Epicardial adipose tissue (EAT) is an active endocrine organ that could contribute to the pathophysiology of coronary artery disease (CAD) through the paracrine release of proatherogenic mediators. Numerous works have analyzed the inflammatory signature of EAT, but scarce informations on its lipidome are available. Our objective was first to study the differences between EAT and subcutaneous adipose tissue (SAT) lipidomes and second to identify the specific untargeted lipidomic signatures of EAT and SAT in CAD. APPROACH AND RESULTS: Subcutaneous and EAT untargeted lipidomic analysis was performed in 25 patients with CAD and 14 patients without CAD and compared with paired plasma lipidomic analysis of isolated VLDL (very low-density lipoprotein) and HDL (high-density lipoprotein). Lipidomics was performed on a C18 column hyphenated to a Q-Exactive plus mass spectrometer, using both positive and negative ionization mode. EAT and SAT had independent lipidomic profile, with 95 lipid species differentially expressed and phosphatidylethanolamine 18:1p/22:6 twenty-fold more expressed in EAT compared with SAT false discovery rate =3×10 −4). Patients with CAD exhibited more ceramides (P=0.01), diglycerides (P=0.004; saturated and nonsaturated), monoglycerides (P=0.013) in their EAT than patients without CAD. Conversely, they had lesser unsaturated TG (triglycerides; P=0.02). No difference was observed in the 295 lipid species found in SAT between patients with and without CAD. Fifty-one lipid species were found in common between EAT and plasma lipoproteins. TG 18:0/18:0/18:1 was found positively correlated (r=0.45, P=0.019) in EAT and HDL and in EAT and VLDL (r=0.46, P=0.02). CONCLUSIONS: CAD is associated with specific lipidomic signature of EAT, unlike SAT. Plasma lipoprotein lipidome only partially reflected EAT lipidome.

show abstract

Section: Discussionmentioning

confidence: 99%

Untargeted Lipidomics Reveals a Specific Enrichment in Plasmalogens in Epicardial Adipose Tissue and a Specific Signature in Coronary Artery Disease

Barchuk

Dutour

Ancel

et al. 2020

ATVB

View full text Add to dashboard Cite

show abstract

“…Signs of SM hydrolysis in lesional LDL (Öörni et al, 1998) as well as ASM-induced LDL aggregation (Walters and Wrenn, 2011), depending on the sphingomyelinaseto-LDL molar ratio (Guarino et al, 2006), confirmed the role of ASM and extended its promotion of aggregation to small very-low-density and intermediate-density lipoprotein particles (Öörni et al, 2005). However, another group detected sphingomyelinase activity as an intrinsic property of the multifunctional LDL constituent apolipoprotein B-100 based on the sequence homology of the apoliprotein B-100 α2 domain with bacterial sphingomyelinase or at least as very tightly associated with LDL and absent in oxidized LDL or other lipoproteins ( Holopainen et al, 2000;Kinnunen and Holopainen, 2002).…”

Section: +mentioning

confidence: 91%

Secretory sphingomyelinase in health and disease

Kornhuber

Rhein

Müller

et al. 2015

Biological Chemistry

122

138

View full text Add to dashboard Cite

Acid sphingomyelinase (ASM), a key enzyme in sphingolipid metabolism, hydrolyzes sphingomyelin to ceramide and phosphorylcholine. In mammals, the expression of a single gene, SMPD1, results in two forms of the enzyme that differ in several characteristics. Lysosomal ASM (L-ASM) is located within the lysosome, requires no additional Zn 2+ ions for activation and is glycosylated mainly with high-mannose oligosaccharides. By contrast, the secretory ASM (S-ASM) is located extracellularly, requires Zn 2+ ions for activation, has a complex glycosylation pattern and has a longer in vivo half-life. In this review, we summarize current knowledge regarding the physiology and pathophysiology of S-ASM, including its sources and distribution, molecular and cellular mechanisms of generation and regulation and relevant in vitro and in vivo studies. Polymorphisms or mutations of SMPD1 lead to decreased S-ASM activity, as detected in patients with Niemann-Pick disease B. Thus, lower serum/ plasma activities of S-ASM are trait markers. No genetic causes of increased S-ASM activity have been identified. Instead, elevated activity is the result of enhanced release (e.g., induced by lipopolysaccharide and cytokine stimulation) or increased enzyme activation (e.g., induced by oxidative stress). Increased S-ASM activity in serum or plasma is a state marker of a wide range of diseases. In particular, high S-ASM activity occurs in inflammation of the endothelium and liver. Several studies have demonstrated a correlation between S-ASM activity and mortality induced by severe inflammatory diseases. Serial measurements of S-ASM reveal prolonged activation and, therefore, the measurement of this enzyme may also provide information on past inflammatory processes. Thus, S-ASM may be both a promising clinical chemistry marker and a therapeutic target.

show abstract

“…Structural studies suggested that LDL binding to lipoprotein lipase is mediated entirely by the lipids and does not involve apoB (48). In vitro study showed that lipoprotein lipase can induce LDL aggregation at higher than equimolar ratios of the enzyme to LDL (49). This suggests that lipoprotein aggregation in these experiments was due to the nonenzymatic anchoring action of lipoprotein lipase.…”

Section: Biochemical Modificationsmentioning

confidence: 99%

Aggregation and fusion of low-density lipoproteins in vivo and in vitro

Gursky

2013

BioMolecular Concepts

View full text Add to dashboard Cite

Low-density lipoproteins (LDLs, also known as ‘bad cholesterol’) are the major carriers of circulating cholesterol and the main causative risk factor of atherosclerosis. Plasma LDLs are 20- to 25-nm nanoparticles containing a core of cholesterol esters surrounded by a phospholipid monolayer and a single copy of apolipoprotein B (550 kDa). An early sign of atherosclerosis is the accumulation of LDL-derived lipid droplets in the arterial wall. According to the widely accepted ‘response-to-retention hypothesis’, LDL binding to the extracellular matrix proteoglycans in the arterial intima induces hydrolytic and oxidative modifications that promote LDL aggregation and fusion. This enhances LDL uptake by the arterial macrophages and triggers a cascade of pathogenic responses that culminate in the development of atherosclerotic lesions. Hence, LDL aggregation, fusion, and lipid droplet formation are important early steps in atherogenesis. In vitro, a variety of enzymatic and nonenzymatic modifications of LDL can induce these reactions and thereby provide useful models for their detailed analysis. Here, we summarize current knowledge of the in vivo and in vitro modifications of LDLs leading to their aggregation, fusion, and lipid droplet formation; outline the techniques used to study these reactions; and propose a molecular mechanism that underlies these pro-atherogenic processes. Such knowledge is essential in identifying endogenous and exogenous factors that can promote or prevent LDL aggregation and fusion in vivo and to help establish new potential therapeutic targets to decelerate or even block these pathogenic reactions.

show abstract

Mechanistic roles of lipoprotein lipase and sphingomyelinase in low density lipoprotein aggregation

Cited by 12 publications

References 29 publications

Untargeted Lipidomics Reveals a Specific Enrichment in Plasmalogens in Epicardial Adipose Tissue and a Specific Signature in Coronary Artery Disease

Untargeted Lipidomics Reveals a Specific Enrichment in Plasmalogens in Epicardial Adipose Tissue and a Specific Signature in Coronary Artery Disease

Secretory sphingomyelinase in health and disease

Aggregation and fusion of low-density lipoproteins in vivo and in vitro

Contact Info

Product

Resources

About