Oxidative Modification of Lipoproteins: A Potential Role of Oxidized Small dense LDL in Enhanced Atherogenicity

Atherosclerosis (AS) is a multifaceted inflammatory syndrome of the arterial wall to which number of mediators have been implicated in lesion progression. Triglyceride (TG)-rich lipoproteins consist of the large diversity of lipoprotein particles that fluctuate in density, size, and apolipoprotein composition. Two foremost phenotypes, on basis of size, chemical configuration, and density, of low-density-lipoprotein (LDL) have been recognized i.e., pattern A, having LDL diameter greater than 25.5nm (large buoyant LDL or lb-LDL) and pattern B, having LDL diameter less than or equal to 25.5nm (small-dense LDL or sd-LDL). Small-dense low-density-lipoprotein (sd-LDL) particles are produced by potential intravascular hydrolysis of TG-rich VLDL particles via lipoprotein lipases (LPLs), hepatic lipases (HLs) and cholesterol ester transfer protein (CETP). sd-LDL is more atherogenic due to its smaller size, increased penetration into the arterial wall, extended plasma half-life, lesser binding affinity for LDL receptors (LDL-R) as well as lower resistance to oxidative stress when equated with lb-LDL. The higher atherogenic potential of sd-LDL is due to its enhanced susceptibility to oxidation, owing to high polyunsaturated fatty acids (PUFA), low cholesterol and Apoprotein B (ApoB) content. An enhanced understanding of sd-LDL metabolism at the molecular level, transport and clearance may result in the development of sd-LDL as an independent predictive marker for AS events and may be used to maintain cholesterol homeostasis and prevent the succession of AS.

Kadar Apoprotein A dan Apoprotein B Serum Darah Tikus Putih (Rattus norvegicus L.) yang diinduksi Pakan Tinggi Lemak Setelah diberi Ekstrak Etanol Daun Mimba (Azadirachta indica)

Penelitian ini bertujuan untuk menguji pengaruh ekstrak etanol daun mimba (Azadirachta indica) terhadap kadar apoprotein A dan apoprotein B tikus putih (Rattus norvegicus L.) yang diberi pakan tinggi lemak. Penelitian menggunakan Rancangan Acak Lengkap, sebanyak 24 ekor tikus putih jantan dewasa digunakan sebagai hewan uji, dibagi 6 perlakuan dan 4 kali ulangan. Perlakuan meliputi P0 (control), P1 (pakan tinggi lemak), P2 (simvastatin 8 mg), P3; P4; dan P5 (uji dosis ekstrak etanol daun mimba 75; 100; dan 125 mg). Hari terakir perlakuan, hewan dikorbankan dan diambil darahnya untuk analisis kadar apoprotein A dan apoprotein B. Kadar apoprotein A dan apoprotein B serum darah ditentukan dengan metode colorimetric enzymatic menggunakan cobas c reagents kits. Kadar apoprotein A dan apoprotein B serum darah diukur dengan menggunakan Roche/Hitachi cobas c systems automatically calculate. Hasil penelitian menunjukkan bahwa pakan tinggi lemak berpengaruh meningkatkan kadar apoprotein B, ekstrak etanol daun mimba berpengaruh meningkatkan kadar apoprotein A dan menurunkan kadar apoprotein B.

Apo A1 / Apo B Ratio and Acute Coronary Syndrome Among Peritoneal Dialysis Patients

Background: Acute coronary syndrome (ACS) is prevalent in continuous ambulatory peritoneal dialysis (CAPD) patients. But the association between apoprotein profile and ACS is not well known. Therefore, we aimed to investigate the relationship between apoproteins and ACS in CAPD patients.Methods: Eighty-one CAPD patients were included in this retrospective study. The primary endpoint was ACS. Predictors were baseline apoprotein levels, particularly the ratio of apoprotein A1 (Apo A1) / apoprotein B (Apo B). Binary logistics regression was used to determine the relationship between Apo A1 / Apo B and ACS. Results: During follow-up, 34 (41.98%) CAPD patients experienced an ACS. ACS patients had higher levels of total cholesterol (p = 0.03), LDL-C (p = 0.04), CRP (p = 0.01), and Apo B (p < 0.01). However, hemoglobin (p = 0.01) and the Apo A1 / Apo B (p < 0.01) were lower in the ACS group than the non-ACS group. Patients with Apo A1 / Apo B ≥ 1.105 experienced fewer ACS compared with those with Apo A1 / Apo B < 1.105 (33.33% vs. 75.56%, p = 0.03). In binary logistics regression, Apo A1 / Apo B (OR, 0.01; 95% CI, 0.00-0.77; p = 0.04) was independently associated with ACS. Conclusions: Apo A1 / Apo B were strongly associated with ACS, and may be considered as a predictor of future ACS in CAPD patients.

CORRELATION BETWEEN APOPROTEIN B/APOPROTEIN A-I RATIO WITH HOMA IR VALUE (HOMEOSTATIC MODEL ASSESMENT INSULIN RESISTANCE) IN TYPE 2 DIABETES MELLITUS

Background: Diabetes mellitus (DM) is the seventh leading cause of death in the world (the occuring rate has reached 400 million people). Type2 DM is caused by the body cells’ inability to respond normally to insulin (insulin resistance). Homeostatic Model Assessment-Insuline Resistance (HOMA-IR) is a calculation method which function is to measure the body insulin resistance. Diabetes mellitus can cause lipid metabolism disorders (dyslipidemia) resulting in an increased level of LDL cholesterol and decreased HDL cholesterol. The apoprotein B/apoprotein A-I ratio is the result of comparisons of apoprotein B (LDL protein constituent) and apoprotein A-I (HDL protein constituent). The apo B/apo A-I ratio represents a balance between LDL cholesterol (atherogenic) and HDL (anti-atherogenic). It is astrong signifier in predicting heart disease. Purpose: This study aim to determine the correlation between the apoprotein B/apoprotein A-I ratio with HOMA-IR in patients with type 2 diabetes mellitus. Methods: Observasional, consecutive, 100 people with type 2 diabetes mellitus who is examined in apoprotein B, apoprotein A-I test that calculating the ratio in which ratio are calculated, as well as HOMA-IR in Parahita Clinical Laboratory Surabaya. This study uses Pearson correlation test method with SPSS 22.0 for Windows program. Results: The result of Pearson correlation test between apoprotein B/apoprotein A-I ratio with HOMA-IR in 100 samples is a strong and significant correlation value (r=0,610, p<0,05).Conclusion: There is a strong correlation between the apoprotein B/apoprotein A-I ratio with HOMA-IR in patients with type 2 diabetes mellitus.

FAMILIAL HETEROZYGOUS HYPERCHOLESTEROLEMIA: A CASE REPORT

Іntroduction: Familial hypercholesterolemia (FH) is an autosomal dominant disorder, caused by the defect of the gene, encoding the structure and function of the receptor for the apoprotein B/E. Patients with FH are predisposed to premature development of atherosclerosis and clinically manifested forms of cardiovascular diseases, in particular coronary heart disease (CHD). The aim of our article is informing the general practitioners about the diagnosis and management of patients with familial heterozygous hypercholesterolemia. Materials and methods: The data of domestic and foreign literature were analyzed. The case report of familial heterozygous hypercholesterolemia (FHH) was present in this article. Diagnostic criteria, current approaches to the management of patients with hereditary disorders of lipid metabolism are considered. Conclusions: Familial heterozygous hypercholesterolemia is one of the most common genetic disorders, but this pathology is not well-known to practitioners and is often underdiagnosed. Early diagnosis and aggressive contemporary hypolipidemic therapy is crucial for patients with signs of hereditary lipid disorders.

Lipoprotein(a) and LDL-Cholesterol Status in type 2 Diabetes Mellitus with Microvascular Complications

The present study was conducted to investigate lipid profile in T2DM patients with microvascular complications such as nephropathy, retinopathy and neuropathy. Case-control observational study in Medical Research Unit (MRU), of Medical and Health Wealfare Trust (MHWT), Uttara, Dhaka, Bangladesh from October 2013 to December 2014; A total of 150 T2DM (Group-B) patients (male: 90, female: 60, age range: 25-65 years) with 30 patients in each sub-group, i.e. without complications (B1), with nephropathy (B2), with retinopathy (B3), with neuropathy (B4) and with multiple complications (B5) and 30 normal controls (male: 18, female: 12, age range: 28-60 years)(Group-A) were included in the study. The lipid profile i.e. triglyceride (TG,) total cholesterol (TC), LDL-C, HDL-C and Lp(a) were quantitatively measured by standard clinical laboratory methods. The findings were compared statistically among patients and controls. Serum lipids i.e. TG, TC, LDL-C and Lp(a) were elevated and HDL-C was decreased in patients (Group -B) compared to controls (Group-A) significantly [Group-A vs Group-B: TG (mg/dl) - 93.7±18.9, 184.4±36.5; TC (mg/dl) - 141.9±25.5, 237.7±69.5; LDL-C (mg/dl) - 85.8±22.1, 165.1±26.3; HDL-C (mg/dl) -47.4±17.4, 35.5±6.6; Lp(a) (mg/l) - 29.1±14.2, 73.5±23.4] (P< 0.001). Among microvascular complications, T2DM-patients with nephropathy (Group-B2) had the highest elevated levels of TG, TC, LDL-C and Lp(a) and maximally decreased level of HDL-C (P< 0.001); Our findings suggest that reduction of all cholesterol-bearing lipoproteins that contain apoprotein B would be important in T2DM with microvascular complications. Possibly Lp(a) reduction and induction of HDL-C are most relevant in this regard.Bangladesh J Med Biochem 2015; 8(2): 66-73