Sex Dimorphism in Serum Lecithin: Cholesterol Acyltransferase and Lipoprotein Lipase Activities in Adult Sickle Cell Anaemia Patients with Proteinuria

Abstract

Proteinuria in subjects with sickle cell anaemia (SCA) is an indication of an ongoing renal insufficiency and it's prevalence varies between sexes. We evaluated sex differences in the activities of Lecithin: cholesterol acyltransferase (LCAT), Lipoprotein lipase (LPL) and the levels of lipoproteins in SCA patients with proteinuria. Fifty SCA patients (30 males aged: 26.4 ± 7.3 years and 20 females, aged 25.4 ± 2.6 years) and 50 age and sex matched control SCA patients were recruited for the study. Random urine specimens were collected and tested for the presence of albumin by urine dipstick technique. A 24 h urinary protein was quantitated using sulphosalicylic acid technique. Fasting serum total cholesterol, triglyceride, urea and creatinine were determined using enzymes catalyzed colorimetric methods. HDL cholesterol was determined in the supernatant after precipitation with manganese chloride-phosphotungstic acid solution. LCAT was measured using the Anasolv LCAT assay with proteoliposome as substrate. LPL was determined by incubating the serum in glyceryl trioleate substrate, the glycerol liberated was measured in an aliquot of the incubating mixture. In male SCA controls there was 18.2 and 6.9% increase in the activities of LPL and LCAT respectively when compared with females but in SCA patients with proteinuria there was 8.4 and 5.2% decreases in the male SCA patients compared with females. The concentration of 24 h urine protein in the SCA male subjects with proteinuria was significantly higher (0.25 g/day; P < 0.001) compared with the SCA female patients with proteinuria (0.09 g/day). There are sex differences in the activities of LCAT and LPL in SCA patients with proteinuria. Metabolism of these lipolytic enzymes may be modulated differently in SCA patients with proteinuria.

High-coverage plasma lipidomics reveals novel sex-specific lipidomic fingerprints of age and BMI: Evidence from two large population cohort studies

“…Lysophosphatidylcholine and ether-linked phospholipids were significantly elevated in the plasma of men compared with women, suggesting there is a sexual dimorphism in phospholipid metabolism, which could be partly due to differences in the activity of phospholipases and/or complex hormonal, dietary, and lifestyle factors. Two phospholipid-metabolising enzymes, lecithin cholesterol acyltransferase (LCAT) [ 35 ] and lipoprotein-associated phospholipase A2 (PLA2) [ 36 ], have been reported to differ between men and women and likely contribute to these lipidomic associations. Indeed, increased activity and/or mass of lipoprotein-associated PLA2 is an independent risk factor for stroke and cardiovascular disease [ 37 , 38 ].…”

The influence of decreased levels of high density lipoprotein cholesterol on hematological indices in sickle cell disease patients

“…In healthy individuals, in the absence of systemic oxidative stress and inflammation, HDL is anti-inflammatory. [ 12 13 14 ] HDL-c is capable of preventing LDL-c oxidation and inflammatory response induced by LDL-c deposition in the endothelial space where the oxidized LDL-c caused the cells to synthesize and secrete monocyte chemoattractant protein-1; which is a potent inflammatory agent as seen in atherosclerosis. [ 15 ] The HDL consists of several particles of different compositions and functions.…”

“…[ 12 13 ] One of such components of HDL is the Lecithin: Cholesterol Acyltransferase; an important enzyme involved in the esterification of cholesterol which had earlier been reported to be low in SCD patients. [ 14 ]…”

Association of Oxidative Stress Markers with Atherogenic Index of Plasma in Adult Sickle Cell Nephropathy

“…Oxidative damage may alter both structure and function of the glomerulus due to its effects on mesangial and endothelial cells. Overexpression of ROS by both enzymatic and nonenzymatic pathways (Fenton chemistry) promotes intravascular oxidant stress that can disrupt nitric oxide homeostasis and produce the highly oxidative peroxynitrite [ 22 ]. Previous reports have showed that renal disease in SCD has the capacity to diminish arginine bioavailability through the loss of de novo arginine synthesis from citrulline which occurs primarily in the kidneys.…”