Increased Low-Density Lipoprotein S-Homocysteinylation in Chronic Kidney Disease

Abstract

Background: Since low-density lipoprotein (LDL) S-homocysteinylation has been recently reported to enhance atherogenicity of lipoprotein, we have investigated the levels of homocysteine (Hcy) linked to LDL in chronic proteinuric patients in which lipid abnormalities highly contribute to the excess of morbidity and mortality. Methods: We used capillary electrophoresis to measure LDL-bound thiol Hcy, cysteine (Cys), cysteinylglycine (Cys-Gly), glutathione (GSH), and glutamylcysteine (Glu-Cys) in 30 chronic kidney disease (CKD) individuals and 60 healthy volunteers. Results: We found more elevated levels of total plasma Hcy, Cys, GSH and Glu-Cys in patients than in controls and also found that Hcy and Cys bound to LDL were significantly increased in nephropathic subjects. By multiple linear regression, we found that in healthy people, total Hcy was the most important determinant of LDL-bound Hcy and Cys-Gly was negatively associated with apoB-Hcy concentrations. In CKD the most important determinant of homocysteinylation was creatinine while total plasma Hcy is weakly associated with apoB-Hcy. Conclusions: The increased levels in Hcy-LDL observed in CKD patients might account, at least in part, for the excess of cardiovascular risk; thus LDL S-homocysteinylation can be considered a key marker of risk for cardiovascular disease in these individuals.

Effects of Ramipril and Telmisartan on Plasma Concentrations of Low Molecular Weight and Protein Thiols and Carotid Intima Media Thickness in Patients with Chronic Kidney Disease

“…Similar results have also been reported for cysteine [13, 14]. In CKD patients both Hcy and Cys plasma concentrations are commonly increased thus contributing, at least in part, to the high cardiovascular risk in this group [15]. Plasma LMW thiols also include cysteinylglycine (CysGly), glutathione (GSH), and glutamylcysteine (Glucys).…”

“…Recruitment was performed as previously described [15]. In brief, 24 CKD hypertensive patients (age 60 ± 12 years, 8 females and 16 males) were identified at the Istituto di Patologia Medica, Azienda Ospedaliero Universitaria, with the following inclusion criteria: age > 18 years, blood pressure ≥ 140/90 mmHg, plasma LDL-cholesterol concentrations > 100 mg/dL (without concomitant hypolipidemic drugs), and presence of proteinuric CKD defined as creatinine clearance > 20 mL/min/1.73 m 2 combined with urinary protein excretion rate > 0.3 g/24 h, without evidence of urinary tract infection or overt heart failure (New York Heart Association class III or more).…”

Homocysteine in Protein Structure/Function and Human Disease

“…S-Hcy-ApoB-100 is reported to be significantly elevated (to 0.024 mol S-linked Hcy/mol ApoB) in chronic kidney disease (CKD) patients in comparison with healthy controls [421]. S-Cys-ApoB-100 is also significantly elevated in these patients to 0.386 mol S-linked Hcy/mol ApoB.…”

Capillary electrophoresis in the analysis of biologically important thiols

“…Biological thiols are present in blood plasma in micromolar concentrations (Hcy ∼ 10 μM, Cys ∼ 250 μM, GSH ∼ 6 μM). In the majority of the methods developed within the reviewed period for plasma/serum, analysis of various thiol forms (reduced, oxidized, protein‐bound, and so on) was by CE‐LIF , but other detection methods such as UV‐Vis , amperometric , and MS were also applied. In few applications various clinical investigations were performed.…”

“…The theoretical knowledge on various thiol separation systems as studied in numerous publications was applied in a wide range of biological samples with clinical importance. Those include thiols in human blood plasma [33,38,[43][44][45][46][47][48][49][50], human whole blood [51], erythrocytes [39,52], carotid atherosclerotic plaques [53,54], cultured cells [40,41,52], and bacteria [42]. Except for endogenous thiols, also pharmaceutical compounds containing thiol moiety such as D-PENA in blood plasma [34], captopril in urine [55], and thiouracil used in the treatment of hyperthyroidism [56] were analyzed after 5-IAF derivatization.…”