scholarly journals Proteomic Characterization of High-Density Lipoprotein Particles from Non-Diabetic Hemodialysis Patients

Toxins ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 671 ◽  
Author(s):  
Florens ◽  
Calzada ◽  
Delolme ◽  
Page ◽  
Guebre Egziabher ◽  
...  

Chronic kidney disease is associated with an increased cardiovascular risk, and altered biological properties of high-density lipoproteins (HDL) may play a role in these events. This study aimed to describe the HDL proteome from non-diabetic hemodialysis patients and identify potential pathways affected by the dysregulated expression of HDL proteins. HDL were sampled from nine non-diabetic hemodialysis (HD) and eight control patients. Samples were analyzed using a nano-RSLC coupled with a Q-Orbitrap. Data were processed by database searching using SequestHT against a human Swissprot database and quantified with a label-free quantification approach. Proteins that were in at least five of the eight control and six of the nine HD patients were analyzed. Analysis was based on pairwise ratios and the ANOVA hypothesis test. Among 522 potential proteins, 326 proteins were identified to be in the HDL proteome from HD and control patients, among which 10 were significantly upregulated and nine downregulated in HD patients compared to the control patients (p < 0.05). Up and downregulated proteins were involved in lipid metabolism, hemostasis, wound healing, oxidative stress, and apoptosis pathways. This difference in composition could partly explain HDL dysfunction in the chronic kidney disease (CKD) population and participate in the higher cardiovascular risk observed in this population.

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 764
Author(s):  
Arianna Strazzella ◽  
Alice Ossoli ◽  
Laura Calabresi

Dyslipidemia is a typical trait of patients with chronic kidney disease (CKD) and it is typically characterized by reduced high-density lipoprotein (HDL)-cholesterol(c) levels. The low HDL-c concentration is the only lipid alteration associated with the progression of renal disease in mild-to-moderate CKD patients. Plasma HDL levels are not only reduced but also characterized by alterations in composition and structure, which are responsible for the loss of atheroprotective functions, like the ability to promote cholesterol efflux from peripheral cells and antioxidant and anti-inflammatory proprieties. The interconnection between HDL and renal function is confirmed by the fact that genetic HDL defects can lead to kidney disease; in fact, mutations in apoA-I, apoE, apoL, and lecithin–cholesterol acyltransferase (LCAT) are associated with the development of renal damage. Genetic LCAT deficiency is the most emblematic case and represents a unique tool to evaluate the impact of alterations in the HDL system on the progression of renal disease. Lipid abnormalities detected in LCAT-deficient carriers mirror the ones observed in CKD patients, which indeed present an acquired LCAT deficiency. In this context, circulating LCAT levels predict CKD progression in individuals at early stages of renal dysfunction and in the general population. This review summarizes the main alterations of HDL in CKD, focusing on the latest update of acquired and genetic LCAT defects associated with the progression of renal disease.


2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Ahmed Bakillah ◽  
Fasika Tedla ◽  
Isabelle Ayoub ◽  
Devon John ◽  
Allen Norin ◽  
...  

Background: Functional abnormalities of high-density lipoprotein (HDL) and elevated concentration of low-density lipoprotein (LDL) could contribute to cardiovascular disease (CVD) in chronic kidney disease (CKD) patients. Both qualitative and quantitative changes in HDL have been described in patients with CKD. Specifically, HDL abundance is reduced and HDL acquires a pro-inflammatory properties. In this study, we hypothesized that a functioning kidney transplant reduces serum nitrated apoA-I concentration. Methods: Concentrations of nitrated apoA-I, nitrated apoB, total apoA-I and total apoB were measured using indirect sandwich ELISA on sera collected from each transplant subject pre-transplant and at 1, 3, and 12 months post-transplant. Patients were excluded if they had a history of diabetes, prednisone dose > 15 mg/day, nephrotic range proteinuria, serum creatinine (Cr) > 1.5mg/dL or active inflammatory disease, or were treated with lipid-lowering medication or HIV protease inhibitors. Paired values of percent nitrated Apo A-I or nitrated apoB before and after kidney transplantation were compared using Wilcoxon signed rank sum test. Results: We screened 75 transplant patients, and 14 were found to meet the selection criteria. Amongst these patients, twelve and eight patients had Cr < 1.5 mg/dL at 3 and 12 months post-transplant, respectively. There was a significant reduction in % nitrated apoA-I at 12 months post-transplant compared to pre-transplant values in patients with Cr<1.5 mg/dL (p=0.04) but neither at 3 months post-transplant nor in patients with Cr >1.5. Reduction of nitrated apoA-I was associated with slight increase in HDL levels 12 months post-transplantation. In contrast to apoA-I, there was no significant change in % nitrated apoB at 3 months and 12 months post-transplant. No significant corelation was observed between nitrated lipoproteins and CRP levels. Conclusion: Patients with well functioning grafts had significant reduction in percent nitrated apoA-I without any effect on apoB nitration 12 months after kidney transplantation. Further studies are needed in a large cohort to determine if nitrated apoA-I can be used as a valuable marker for cardiovascular risk stratification in CKD.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Daniele La Russa ◽  
Daniela Pellegrino ◽  
Alberto Montesanto ◽  
Paolo Gigliotti ◽  
Anna Perri ◽  
...  

During chronic kidney disease, the progressive deterioration of renal function induces several biological/clinical dysfunctions, including enhancement of synthesis of inflammation/oxidative stress mediators. Impaired renal function is an independent cardiovascular risk factor; indeed, cardiovascular complications dominate the landscape of both chronic kidney disease and end-stage renal disease. The aim of this study is to explore the correlation between the global oxidative balance in hemodialysis patients and both inflammatory markers and cardiovascular events. Using photometric tests, this study explored plasmatic oxidative balance in 97 hemodialysis patients compared to a healthy population. In the hemodialysis patients, we showed that oxidative stress values were significantly lower than in controls while effectiveness in the antioxidant barrier was significantly increased in the hemodialysis group. Furthermore, we highlighted a strong correlation between oxidative index and blood levels of C-reactive protein. When patients were divided into two groups based on previous cardiovascular events, we found that subjects with previous cardiovascular events had higher values of both oxidative stress and antioxidant barrier than patients without cardiovascular events. Our results indicated that in hemodialysis patients, the clinical and prognostic significance of oxidative status is very different from general population. As cardiovascular complications represent a strong negative factor for survival of hemodialysis patients, the research of new cardiovascular risk biomarkers in these patients takes on particular importance in order to translate them into clinical practice/primary care.


Angiology ◽  
2009 ◽  
Vol 60 (5) ◽  
pp. 644-649 ◽  
Author(s):  
Thomas F. Whayne

High-density lipoproteins are regarded as “good guys” but not always. Situations involving high-density lipoproteins are discussed and medication results are considered. Clinicians usually consider high-density lipoprotein cholesterol. Nicotinic acid is the best available medication to elevate high-density lipoprotein cholesterol and this appears beneficial for cardiovascular risk. The major problem with nicotinic acid is that many patients do not tolerate the associated flushing. Laropiprant decreases this flushing and has an approval in Europe but not in the United States. The most potent medications for increasing high-density lipoprotein cholesterol are cholesteryl ester transfer protein inhibitors. The initial drug in this class, torcetrapib, was eliminated by excess cardiovascular problems. Two newer cholesteryl ester transfer protein inhibitors, R1658 and anacetrapib, initially appear promising. High-density lipoprotein cholesterol may play an important role in improving cardiovascular risk in the 60% of patients who do not receive cardiovascular mortality/morbidity benefit from low-density lipoproteins reduction by statins.


2020 ◽  
Vol 14 (5) ◽  
pp. 730-739
Author(s):  
Kotoko Yamatani ◽  
Satoshi Hirayama ◽  
Utako Seino ◽  
Akiko Hirayama ◽  
Atsushi Hori ◽  
...  

2016 ◽  
Vol 88 (9) ◽  
pp. 111-118 ◽  
Author(s):  
Ya D Babintseva ◽  
L Camont ◽  
J Chapman ◽  
M Lhomme ◽  
V P Karagodin ◽  
...  

Increasing the human plasma concentration of high-density lipoproteins (HDL) may be part of strategy for control of cardiovascular diseases (CVD). HDL particles vary in their structure, metabolism, and biological activity. The review describes major HDL fractions (subpopulations) and discusses new findings on the antiatherogenic properties of HDL particles. The whole spectrum of HDL fractions, small, dense, protein-rich lipoproteins, has atheroprotective properties that are determined by the presence of specialized groups of proteins and lipids; however, this activity may be decreased in atherogenic lesion. Comprehensive structural and compositional analysis of HDL may provide key information to identify the fractions that have characteristic biological properties and lose their functionality in CVD. These fractions may be also biomarkers for the risk of CVD and hence represent pharmacological targets.


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