scholarly journals Relationship between COVID-19 and HDL dysfunction

2021 ◽  
Vol 12 (08) ◽  
Keyword(s):  
Hdl Dysfunction

Abstract 454: High Density Lipoprotein Proteome Dynamics is Altered in Non-alcoholic Fatty Liver Disease

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Takhar Kasumov
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Oxidase Activity ◽  
Fatty Liver Disease ◽  
Metabolic Labeling ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Inflammatory Index ◽  
Complement 3 ◽  
Hdl Dysfunction

Objectives: Nonalcoholic fatty liver disease (NAFLD) is associated with an increased rate of cardiovascular disease (CVD) related mortality. HDL protects against CVD through reverse cholesterol transport, anti-oxidant and anti-inflammatory functions. HDL functions and the proteome composition are altered in CVD. We used 2 H 2 O metabolic labeling approach to test hypothesis that altered HDL proteome dynamics is involved in HDL dysfunction in NAFLD. Methods: The kinetics of HDL proteins were measured in patients NAFLD (n=12) and healthy controls (n=8). Each subject consumed 2 H 2 O in their drinking water and blood samples were collected at different time points during one week. 2 H-enrichment of tryptic peptides from HDL proteins were analyzed by mass spectrometry. Oxidase activity of HDL-associated ceruloplasmin (Cp) and HDL’s inflammatory index were quantified using spectrophotometric assays. Results: Compared to control, NAFLD had higher BMI, Hba1c, HOMA-IR, plasma AST, ALT and triglycerides, but similar LDL and HDL cholesterol. NAFLD also had higher inflammatory index (1.8±0.5 vs 1.2±0.2 RUF/mgHDLc/min, p<0.05) and oxidase activity of Cp (93.7±61.2 vs 61.2 U/L, p<0.005). This was associated with increased serum actvity of MPO (6.2±1.2 vs 8.4±1.6, p<0.05), a nutrophile-derived protein involved in HDL dysfunction. HDL NAFLD was significantly enriched with proteins involved in the acute phase response (complement 3, Cp) but depleted in apoAII and PON1. These changes were associated with increased fractional catabolic rates (FCRs) of apoAI (1.6±0.2 vs 1.1±0.3 %/h), apoAII (1.6±0.2 vs 1.1±0.3 %/h), apoAIV (2.6±0.8 vs 3.9±0.7%/h) and increased relative production rate (RPR) of complement 3 (>4 fold). Oxidase activity of Cp was positively associated with FCR of apoAI (r=0.53, p=0.002) and RPR of C3 (r=0.32, p=0.03). Conclusions: HDL dysfunction in NASH could be related to the altered turnover of HDL proteins, including increased degradation of apoAI, apoAII, apoAIV and increased production of C3.

scholarly journals The HDL dysfunction gains momentum: is it time for a new approach in rheumatic diseases?

Rheumatology ◽  
2020 ◽  
Vol 59 (11) ◽  
pp. 3121-3123
Author(s):  
Javier Rodríguez-Carrio ◽  
Ana Suárez
Keyword(s):  
Rheumatic Diseases ◽  
New Approach ◽  
Hdl Dysfunction

scholarly journals Glycation Reduces the Stability of ApoAI and Increases HDL Dysfunction in Diet-Controlled Type 2 Diabetes

2017 ◽  
Vol 103 (2) ◽  
pp. 388-396 ◽  
Author(s):  
Sangeeta R Kashyap ◽  
Abdullah Osme ◽  
Serguei Ilchenko ◽  
Makan Golizeh ◽  
Kwangwon Lee ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Hdl Dysfunction ◽  
The Stability

Fasting, non-fasting glucose and HDL dysfunction in risk of pre-diabetes, diabetes, and coronary disease in non-diabetic adults

2011 ◽  
Vol 50 (4) ◽  
pp. 519-528 ◽  
Author(s):  
Altan Onat ◽  
Günay Can ◽  
Gökhan Çiçek ◽  
Erkan Ayhan ◽  
Yüksel Doğan ◽  
...  
Keyword(s):  
Coronary Disease ◽  
Fasting Glucose ◽  
Hdl Dysfunction

scholarly journals Mass Spectrometry-Based Proteomic Study Makes High-Density Lipoprotein a Biomarker for Atherosclerotic Vascular Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Chiz-Tzung Chang ◽  
Chao-Yuh Yang ◽  
Fuu-Jen Tsai ◽  
Shih-Yi Lin ◽  
Chao-Jung Chen
Keyword(s):  
Mass Spectrometry ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Atherosclerotic Vascular Disease ◽  
Future Directions ◽  
Recent Developments ◽  
Proteomic Study ◽  
Hdl Dysfunction ◽  
Apoprotein Composition

High-density lipoprotein (HDL) is a lipid and protein complex that consists of apolipoproteins and lower level HDL-associated enzymes. HDL dysfunction is a factor in atherosclerosis and decreases patient survival. Mass spectrometry- (MS-) based proteomics provides a high throughput approach for analyzing the composition and modifications of complex HDL proteins in diseases. HDL can be separated according to size, surface charge, electronegativity, or apoprotein composition. MS-based proteomics on subfractionated HDL then allows investigation of lipoprotein roles in diseases. Herein, we review recent developments in MS-based quantitative proteomic techniques, HDL proteomics and lipoprotein modifications in diseases, and HDL subfractionation studies. We also discuss future directions and perspectives in MS-based proteomics on HDL.

scholarly journals 4-oxo-2-nonenal Adducts In HDL Are Elevated In Familial Hypercholesterolemia: Identification Of Modified Sites And Functional Consequences

2019 ◽  
Author(s):  
Linda S. May-Zhang ◽  
Valery Yermalitsky ◽  
John T. Melchior ◽  
Jamie Morris ◽  
Keri A. Tallman ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Fatty Acids ◽  
Familial Hypercholesterolemia ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Healthy Controls ◽  
Reactive Protein ◽  
Macrophage Cholesterol Efflux ◽  
Hdl Dysfunction ◽  
Functional Consequences

ABSTRACTThe lipid aldehyde 4-oxo-2-nonenal (ONE) derived from peroxidation of n-6 polyunsaturated fatty acids and generated in parallel to 4-hydroxynonenal (HNE) is a highly reactive protein crosslinker. Crosslinking of proteins in high-density lipoprotein (HDL) by lipid peroxidation products causes HDL dysfunction and contributes to atherogenesis. While HNE is relatively well studied, the relevance of ONE in atherosclerosis and in modifying HDL has not been examined. In the present study, we found a significant increase in ONE-ketoamide (lysine) adducts in HDL derived from patients with familial hypercholesterolemia (FH) (1620 ± 985.4 pmol/mg) compared to healthy controls (664 ± 219.5 pmol/mg). ONE crosslinked apoA-I on HDL at a concentration of >3 mol ONE per 10 mol apoA-I (0.3 eq), which is 100-fold lower than HNE but comparable to the potent protein crosslinker, isolevuglandin. ONE-modified HDL partially inhibited the ability of HDL to protect against LPS-induced TNFα and IL-1β mRNA expression in murine macrophages. At 3 eq., ONE dramatically decreased the ability of apoA-I to exchange from HDL, from ~46.5% to only ~18.4% (P<0.001). Surprisingly, ONE-modification of HDL or apoA-I did not alter macrophage cholesterol efflux capacity. LC/MS/MS analysis showed modification of Lys12, Lys23, Lys96, and Lys226 of apoA-I by ONE-ketoamide adducts. Compared to other dicarbonyl scavengers, pentylpyridoxamine (PPM) was most efficacious at blocking ONE-induced protein crosslinking in HDL. Our studies show that ONE HDL adducts are elevated in FH who have severe hypercholesterolemia and atherosclerosis and causes HDL dysfunction. We demonstrate the use of PPM in preferentially scavenging ONE in biological systems.

Dysfunctional HDL as a Therapeutic Target for Atherosclerosis Prevention

2019 ◽  
Vol 26 (9) ◽  
pp. 1610-1630 ◽  
Author(s):  
Alice Ossoli ◽  
Chiara Pavanello ◽  
Eleonora Giorgio ◽  
Laura Calabresi ◽  
Monica Gomaraschi
Keyword(s):  
Reverse Cholesterol Transport ◽  
High Density Lipoproteins ◽  
Cholesterol Transport ◽  
Hdl Function ◽  
Investigational Drugs ◽  
Hdl Dysfunction ◽  
Atherosclerosis Prevention ◽  
Endothelial Homeostasis ◽  
Dysfunctional Hdl

Hypercholesterolemia is one of the main risk factors for the development of atherosclerosis. Among the various lipoprotein classes, however, high density lipoproteins (HDL) are inversely associated with the incidence of atherosclerosis, since they are able to exert a series of atheroprotective functions. The central role of HDL within the reverse cholesterol transport, their antioxidant and anti-inflammatory properties and their ability to preserve endothelial homeostasis are likely responsible for HDL-mediated atheroprotection. However, drugs that effectively raise HDL-C failed to result in a decreased incidence of cardiovascular event, suggesting that plasma levels of HDL-C and HDL function are not always related. Several evidences are showing that different pathologic conditions, especially those associated with an inflammatory response, can cause dramatic alterations of HDL protein and lipid cargo resulting in HDL dysfunction. Established and investigational drugs designed to affect lipid metabolism and to increase HDL-C are only partly effective in correcting HDL dysfunction.

scholarly journals Role of HDL Dysfunction in End-Stage Renal Disease: A Double-Edged Sword

2013 ◽  
Vol 23 (3) ◽  
pp. 203-206 ◽  
Author(s):  
Hamid Moradi ◽  
Nosratola D. Vaziri ◽  
Moti L. Kashyap ◽  
Hamid M. Said ◽  
Kamyar Kalantar-Zadeh
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Hdl Dysfunction ◽  
Stage Renal Disease ◽  
End Stage
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