Hyperlipidemias: Zhao HL

Critchley JA, Zhao HL, Tomlinson B, Leung W, Thomas GN, Chan JC, Cockram CS. · Divisions of Clinical Pharmacology and Endocrinology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong, China. · Chin Med J (Engl). · Pubmed #11930647 links to  free full text

Abstract: PURPOSE: To review evidence-based management of nephropathy in patients with type 2 diabetes. DATA SOURCES: A literature search (MEDLINE 1966 to 2000) was performed using the key word "diabetic nephropathy". Relevant book chapters were also reviewed. STUDY SELECTION: Well-controlled, prospective landmark studies and expert review articles on diabetic nephropathy were selected. DATA EXTRACTION: Data and conclusions from the selected articles that provide solid evidence to the optimal management of diabetic nephropathy were extracted and interpreted in light of our clinical research experience with many thousands of Hong Kong Chinese patients. RESULTS: Hypertension, long diabetes duration, poor glycaemic control and central obesity are the most important risk factors. Microalbuminuria is a practical marker to predict overt nephropathy in type 2 diabetic patients. Risk factor modification, renal function monitoring and combined therapies are the current integrated approaches to manage patients with diabetic kidney disease. Optimal glycaemic control is the mainstay of treatment but effective antihypertensive therapy is also key to delaying the progression of diabetic nephropathy. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists have important renoprotective actions independent of their blood pressure lowering actions. CONCLUSIONS: Diabetic nephropathy is the leading cause of end-stage renal disease worldwide. Monitoring renal function and screening for microalbuminuria will allow the identification of patients with nephropathy at a very early stage for intervention. Tight glycaemic control and aggressive antihypertensive treatment as well as the use of renin-angiotensin system inhibitors should substantially delay the progression of nephropathy.

Zhao HL, Houweling AH, Vanstone CA, Jew S, Trautwein EA, Duchateau GS, Jones PJ. · Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, 196 Innovation Drive, Winnipeg, MB, R3T 6C5, Canada. · Lipids. · Pubmed #18850127 No free full text.

Abstract: ATP-binding cassette hetero-dimeric transporters G5 and G8 (ABCG5/G8) have been postulated to mediate intestinal cholesterol efflux, whereas Niemann-Pick C1 Like 1 (NPC1L1) protein is believed to be essential for intestinal cholesterol influx. The individual or combined genetic markers, such as single nuclear polymorphisms (SNPs), of these two transporter genes may explain inter-individual variations in plasma cholesterol response following plant sterol (PS) intervention. The present study was aimed at investigating the association between ABCG5/G8 and NPC1L1 genotype SNPs with sterol absorption and corresponding plasma concentrations. The study used a 4-week crossover design with 82 hypercholesterolemic men characterized by high vs. low basal plasma PS concentrations consuming spreads with or without 2 g/day of PS. For the ABCG8 1289 C > A (T400 K) polymorphism, the A allele carriers with high basal plasma PS concentrations demonstrated a 3.9-fold greater reduction (p < 0.05) in serum low density lipoprotein cholesterol (LDL-C) than their low basal plasma PS counterparts. For the NPC1L1 haplotype of 872 C > G (L272L) and 3929 G > A (Y1291Y), individuals carrying mutant alleles showed a 2.4-fold greater (p < 0.05) reduction in LDL-C levels, compared to wild type counterparts. Results suggest that genetic and metabolic biomarkers together may predict inter-individual lipid level responsiveness to PS-intervention, and thus could be useful in devising individualized cholesterol lowering strategies.

Zhao HL, Sui Y, Guan J, He L, Zhu X, Fan RR, Xu G, Kong AP, Ho CS, Lai FM, Rowlands DK, Chan JC, Tong PC. · Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. · Kidney Int. · Pubmed #18496513 No free full text.

Abstract: Dyslipidemia complicates renal function leading to disturbances of major homeostatic organs in the body. Here we examined the effect of chronic renal dysfunction induced by uninephrectomy on fat redistribution and lipid peroxidation in rats treated with an angiotensin-converting enzyme (ACE) inhibitor (lisinopril) for up to 10 months. Uninephrectomized rats developed fat redistribution and hypercholesterolemia typical of chronic renal failure when compared with sham-operated rats or lisinopril-treated uninephrectomized rats. The weight of the peri-renal fat was significantly less in the untreated compared to the lisinopril-treated uninephrectomized rats or those rats with a sham operation. We also found that there was a shift of heat-protecting unilocular adipocytes to heat-producing multilocular fat cells in the untreated uninephrectomized rats. Similarly in these rats we found a shift of subcutaneous and visceral fat to ectopic fat with excessive lipid accumulation and lipofuscin pigmentation. Lisinopril treatment prevented fat redistribution or transformation and lipid peroxidation. This study shows that ACE inhibition may prevent the fat anomalies associated with chronic renal dysfunction.

Zhao HL, Cho KH, Ha YW, Jeong TS, Lee WS, Kim YS. · Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 110-460, Republic of Korea. · Eur J Pharmacol. · Pubmed #16626693 No free full text.

Abstract: This study investigates the in vivo hypocholesterolemic action of platycodin D and its in vitro evidence for the cholesterol-lowering properties. In order to examine the effects of platycodin D on hypercholesterolemia in male ICR mice, platycodin D with doses of 15, 30 or 50 mg/kg was orally administered for 8 weeks. Changes in body weight and daily food intake were measured regularly during the experimental period. Final contents of triglyceride and different types of cholesterol in the serum, livers and feces were determined. The effects of platycodin D on cholesterol metabolism were further investigated with several in vitro assays, including antioxidant effect on low density lipoprotein oxidation, inhibition of human acyl-coenzyme A:cholesterol acyltransferase (hACAT) and serum lipoprotein associated-phospholipase A(2) (Lp-PLA(2)), as well as the regulation of farnesoid X receptor. The formation of insoluble complex between platycodin D and cholesterol was also investigated. Following an eight week experimental period, the body weights of platycodin D-fed mice were less than those of control mice on a high cholesterol diet by 11.2+/-5% (P<0.01) with 15 mg/kg platycodin D, 11.7+/-5% (P<0.01) with 30 mg/kg platycodin D, and 23.4+/-7.9% (P<0.0001) with 50 mg/kg platycodin D, respectively. A decrease in daily food consumption was also noted in most of the treated animals. Triglyceride and cholesterol concentrations were decreased in serums and livers, but increased in feces. Some of the in vitro observations revealed that the hypocholesterolemic effect of platycodin D is partly associated with inhibition to hACAT activity and antagonism to the farnesoid X receptor as well as the formation of insoluble complex with between platycodin D and cholesterol. Both in vivo and in vitro results demonstrate a potential value of platycodin D as a novel cholesterol-lowering and anti-atherogenic candidate.