Patients with nephrotic-range proteinuria have apolipoprotein C and E deficient VLDL1.
BACKGROUND
Impaired very low-density lipoprotein (VLDL) clearance contributes to dyslipidemia in nephrotic-range proteinuria. VLDL can be subdivided into large light VLDL1 (Sf 60 to 400) and smaller, denser VLDL2 (Sf 20 to 60). In nephrotic-range proteinuria, the clearance of VLDL1 is delayed. VLDL1 lipolysis is influenced by apolipoprotein CII (apoCII) and apoCIII, whereas apoE regulates receptor-mediated clearance.


METHODS
To ascertain whether impaired VLDL1 clearance was related to a deficiency in apolipoproteins on VLDL1, we measured VLDL subfraction concentrations and VLDL1 apolipoprotein and lipid compositions in 27 patients with glomerular disease and urinary albumin> 2 g/24 h along with 27 age- and sex-matched controls.


RESULTS
Proteinuric patients had increased plasma VLDL1, VLDL2, apoCII, apoCIII (all P < 0.001), and apoE concentration (P < 0.002). Patients appeared to have smaller VLDL1 particles, as assessed by triglyceride per particle (median + interquartile range, moles per VLDL1 particle): patients, 4.9 (3.0 to 7.9) x103; controls, 7.0 (4.6 to 15.7) x103, P < 0.05, with reduced apoCII, 4.2 (3.1 to 8.2) versus 9.9 (7.4 to 23.2), P < 0.0004; apoCIII, 16.6 (9.1 to 27.2) versus 29.3 (18.5 to 69.4), P < 0.02; and apoE content, 0.17 (0.08 to 0.44) versus 0.48 (0.31 to 1. 31), P < 0.006. The VLDL1 surface free cholesterol to phospholipid results were increased in proteinuric patients (0.55 +/- 0.17 vs. 0. 40 +/- 0.18, P < 0.002, all mean +/- SD). For all patients, VLDL1 apoCII, apoCIII, and apoE contents per particle were related to particle size (apoCII, r2 = 61.5%, P < 0.001; apoCIII, r2 = 75.8%, P < 0.001; apoE, r2 = 58.2%, P < 0.001) and inversely to the free cholesterol to phospholipid ratio (apoCII, r2 = 41.6%, P < 0.001; apoCIII, r2 = 38.8%, P < 0.001; apoE, r2 = 11.7%, P < 0.05). Multivariate analysis suggested that the relative lack of apoCII and apoCIII on patients VLDL1 was related to smaller particle size and increased free cholesterol:phospholipid (FC:PL) ratio. Particle size but not free cholesterol determined the apoE content of VLDL1.


CONCLUSIONS
We postulate that impaired VLDL1 clearance in nephrotic-range proteinuria results from the appearance of particles deficient in apoCII, apoCIII, and apoE. VLDL1 apoC deficiency is associated with the formation of smaller particles with a high FC:PL ratio, and is likely to cause inefficient lipolysis. VLDL1 apoE deficiency is associated with smaller VLDL1 particles but not altered VLDL1 surface lipid content, and may reduce receptor-mediated clearance of this lipoprotein.
Deighan
C J
CJ
Renal Unit, Glasgow Royal Infirmary and Department of Pathological Biochemistry, University of Glasgow, Glasgow Royal Infirmary, Scotland, United Kingdom. cdeighan@compuserve.com
Caslake
M J
MJ
McConnell
M
M
Boulton-Jones
J M
JM
Packard
C J
CJ
D000328:Adult; D000419:Albuminuria / Q000097:blood; D001056:Apolipoproteins C / Q000097:blood*; D001057:Apolipoproteins E / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood; D008066:Lipolysis / Q000502:physiology; D008079:Lipoproteins, VLDL / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009404:Nephrotic Syndrome / Q000097:blood*; D011507:Proteinuria / Q000097:blood*; D014280:Triglycerides / Q000097:blood
D001056:Apolipoproteins C; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides