Hyperlipidemia in the Nephrotic Syndrome

Acyl-Coenzyme A:Cholesterol Acyltransferase Inhibition Ameliorates Proteinuria, Hyperlipidemia, Lecithin-Cholesterol Acyltransferase, SRB-1, and Low-Denisty Lipoprotein Receptor Deficiencies in Nephrotic Syndrome

“…47 Maturation of HDL-3 to HDL-2 is impaired in NS. [1][2][3][4]14 This is because of acquired LCAT deficiency, which was nearly corrected by ACAT inhibitor.…”

“…H eavy glomerular proteinuria, known as nephrotic syndrome (NS), is associated with hyperlipidemia, [1][2][3][4] increased risk of cardiovascular disease, and deterioration of renal function. 5,6 Nephrotic dyslipidemia is marked by hypercholesterolemia; hypertriglyceridemia; elevated plasma concentration and impaired clearance of LDL, VLDL, and IDL; impaired maturation and diminished clearance of HDL; and increased plasma lipoprotein (a).…”

“…5,6 Nephrotic dyslipidemia is marked by hypercholesterolemia; hypertriglyceridemia; elevated plasma concentration and impaired clearance of LDL, VLDL, and IDL; impaired maturation and diminished clearance of HDL; and increased plasma lipoprotein (a). [1][2][3][4] These abnormalities are largely a result of dysregulation of the key enzymes and receptors involved in lipid metabolism: (1) LDL receptor deficiency, 7,8 which, in part, accounts for elevated plasma level and impaired clearance of LDL 3,9,10 ; (2) lecithin-cholesterol acyltransferase (LCAT) deficiency, 11 elevated plasma cholesterol ester transfer protein (CETP), 12 and diminished hepatic SRB-1 (HDL receptor), 13 which collectively accounts for abnormal composition, impaired maturation, and defective clearance of HDL 3,14 -16 ; (3) dysregulation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol 7␣-hydroxylase (rate-limiting enzyme in cholesterol conversion to bile acid), leading to development and maintenance of hypercholesterolemia 8,17,18 ; (4) upregulations of hepatic biosynthesis and diminished catabolism of apolipoprotein (apo) B-100 and increased production of lipoprotein (a), which contribute to their elevated plasma levels in NS 19,20 ; and (5) downregulations of lipoprotein lipase (LPL) VLDL receptor [21][22][23] and hepatic lipase 24,25 coupled with upregulations of hepatic acylcoenzyme A:diacylglycerol acyltransferase (DGAT, the final step in triglyceride biosynthesis), 26 acetyl-coenzyme A carboxylase, and fatty acid synthase (key enzymes in fatty acid production). 27 These abnormalities account for increased hepatic synthesis, 28 -30 impaired clearance, and elevated plasma triglycerides, VLDL, and IDL in NS (reviewed in Reference 1).…”

A Case of Marked Hyperlipoprotein(a)emia Associated with Nephrotic Syndrome and Advanced Atherosclerosis

“…In the present study, we found that Lp(a) levels were relatively closely correlated with the levels of plasma TC and albumin. It has been proposed that hypoalbuminemia and reduced oncotic pressure stimulate hepatic synthesis of albumin and other liver-derived proteins, such as apoproteins (14). However, the precise mechanism driving the increased synthesis of Lp(a) has not yet been clarified.…”

Effects of lovastatin on hepatic expression of the low-density lipoprotein receptor in nephrotic rats

“…Previous studies suggest that hypercholesterolemia in nephrotic syndrome is the result of the following events and mechanisms: 1) Activity of hepatic HMG-CoA, the rate-limiting enzyme in cholesterol biosynthesis, is increased (Vaziri and Liang, 1995;Vaziri et al, 2003); 2) levels of the LDL receptor, the main route of eliminating cholesterol-rich LDL particles, are decreased ; 3) expression of acyl-CoA cholesteryl ester acyl transferase (ACAT), an enzyme of the endoplasmic reticulum that transfers the acyl-CoA acyl to 3 locations of free cholesterol and leads to cholesterol esterification and cholesterol storage in the cytosol, is upregulated (Vaziri and Liang, 2002); 4) expression of lecithin cholesterol acyl transferase (LCAT), which transfers fatty acids from lecithin on HDL to free cholesterol and contributes to the transfer of esterified cholesterol from the HDL core to the HDL surface during HDL maturation and reverse cholesterol transport (Vaziri et al, 2001), is decreased; 5) a compensatory increase in the activity of hepatic cholesterol 7а-hydroxylase, the rate-limiting enzyme for the conversion of cholesterol to bile acids, is only limited ; and 6) liver apolipoprotein B100 (Apo-B100), which is the major apolipoprotein of LDL and a very LDL (VLDL), is upregulated (Kaysen, 1991). Therefore, as mentioned above, the LDL receptor plays an important role in the formation of hypercholesterolemia in nephrotic syndrome.…”