Uremia Alters HDL Composition and Function

Abstract

Functional impairment of HDL may contribute to the excess cardiovascular mortality experienced by patients with renal disease, but the effect of advanced renal disease on the composition and function of HDL is not well understood. Here, we used mass spectrometry and biochemical analyses to study alterations in the proteome and lipid composition of HDL isolated from patients on maintenance hemodialysis. We identified a significant increase in the amount of acute phase protein serum amyloid A1, albumin, lipoprotein-associated phospholipase A2, and apoC-III composing uremic HDL. Furthermore, uremic HDL contained reduced phospholipid and increased triglyceride and lysophospholipid. With regard to function, these changes impaired the ability of uremic HDL to promote cholesterol efflux from macrophages. In summary, the altered composition of HDL in renal disease seems to inhibit its cardioprotective properties. Assessing HDL composition and function in renal disease may help identify patients at increased risk for cardiovascular disease.

The Effects of Resistance and Endurance Training on the Liver Tissue FNDC5 mRNA Gene Expression in Male Rats

“…HDL cholesterol acts against arthrosclerosis through its antiinflation and control function on the process of cholesterol transfer (40). In accordance with previous research, the indirect correlation between the level of intra-liver triglyceride and irisin and the direct correlation between irisin and HDL can reinforce irisin's protective potential particularly in people with such chronic diseases as NAFLD, which generate cardiovascular risks (41). Irisin can directly or indirectly prevent the accumulation of triglyceride in the liver.…”

HDL abnormalities in nephrotic syndrome and chronic kidney disease

“…This effect is associated with elevated HDL triglyceride and reduced HDL phospholipid contents, a diminished cholesterol ester-rich: cholesterol ester-poor HDL ratio 4,6,53,54 , and impaired HDL antioxidant, anti-inflammatory, and reverse cholesterol transport capacity 55,56 . Although HDL cholesterol is reduced in the majority of patients with ESRD, a proportion of patients show a marked elevation in HDL cholesterol that is paradoxically associated with increased cardiovascular and overall morbidity and mortality [57][58][59] .…”

“…HDL abnormalities contribute to CKD-induced impairment of VLDL and chylomicron metabolism, which primarily result from reduced LPL and hepatic lipase expression and activity 83,105 . Reductions in the ApoC-2 (the LPL cofactor) and ApoE (the ligand for endothelial binding) contents of VLDL and chylomicrons contribute to diminished LPL activity in CKD 55 . These abnormalities are primarily caused by a CKD-induced defect in the maturation of HDL3 to HDL2, which serves as an ApoC and ApoE donor to nascent VLDL and chylomicrons.…”

HDL-cholesterol levels and mortality in patients with ESRD

“…Maturation of cholesterol ester (CE)-poor HDL3 to CE-rich HDL2 is impaired, and HDL antioxidant, anti-inflammatory and reverse cholesterol transport properties are defective in the ESRD population. [3][4][5] Abnormalities of HDL structure and function in advanced CKD are mediated by a reduction in the serum levels of apoA-I and apoA-II (owing to reduced biosynthesis and increased catabolism), deficiency of lecithin cholesterol acyltransferase (LCAT, which is essential for esterification of free cholesterol on the surface of HDL and the formation of CE-rich HDL), upregulation of acyl c oenzyme A:cholesterol acyltransferase 1 and 2 (ACAT-1 and 2, which promote esterification and retention of intracellular cholesterol), oxidative modification of HDL 3,4 (which lowers its affinity for binding to ATPbinding cassette sub-family A member 1 [ABCA1] and ATP-binding cassette subfamily G member 1, the gateways of cholesterol efflux), 6 a reduction in the levels of the key HDL-associated antioxidant enzymes, serum paraoxonase/arylesterase 1 and glutathione peroxidase 1, 4,5 and the presence of highly proinflammatory serum amyloid A protein (SAA) in the HDL of patients on haemodialysis. 7 Hypoalbuminaemia (caused by systemic inflammation and malnutrition, which are fairly common in patients with ESRD) also contributes to reduced HDL-cholesterol levels by limiting receptorindependent transfer of albumin-bound chol esterol to HDL in the blood stream.…”