OBJECTIVE To determine effects of single ascending doses of MDCO-216 on high-density lipoprotein (HDL) subfractions in relation to changes in cholesterol efflux capacity in healthy volunteers and in patients with stable angina pectoris. APPROACH AND RESULTS Doses of 5- (in volunteers only), 10-, 20-, 30-, and 40-mg/kg MDCO-216 were infused during 2 hours, and plasma and serum were collected d...

To study the mechanisms of hepatic HDL formation, we investigated the roles of ABCA1, ABCG1, and SR-BI in nascent HDL formation in primary hepatocytes isolated from mice deficient in ABCA1, ABCG1, or SR-BI and from wild-type (WT) mice. Under basal conditions, in WT hepatocytes, cholesterol efflux to exogenous apoA-I was accompanied by conversion of apoA-I to HDL-sized particles. LXR activation ...

Low levels of high-density lipoprotein cholesterol (HDL-C) represent a major cardiovascular risk factor that is only modestly influenced by currently available drugs. Consequently, there has been interest in developing new therapeutic agents specifically targeting HDL-C to reduce risk in patients with coronary artery disease. One strategy involves the administration of therapies that mimic HDL-...

Receptors that endocytose high-density lipoproteins (HDL) have been elusive. Here yolk-sac endoderm-like cells were used to identify an endocytic receptor for HDL. The receptor was isolated by HDL affinity chromatography and identified as cubilin, the recently described endocytic receptor for intrinsic factor-vitamin B(12). Cubilin antibodies inhibit HDL endocytosis by the endoderm-like cells a...

Wolman disease is a very rare autosomal recessive genetic disorder. The patients have the typical clinical finding of hepatosplenomegaly but with an abnormal lipid profile high levels total cholesterol (TC), triglycerides, and low-density lipoprotein (LDL-C), low level high-density (HDL-C). We report 1-month-old boy who had atypical TC level, both LDL-C HDL-C. study revealed compound heterozygo...

The knowledge of an inverse relationship between plasma high-density lipoprotein cholesterol (HDL-C) concentrations and rates of cardiovascular disease has led to the concept that increasing plasma HDL-C levels would be protective against cardiovascular events. Therapeutic interventions presently available to correct the plasma lipid profile have not been designed to specifically act on HDL, bu...

BACKGROUND The inverse relationship between high-density lipoprotein (HDL) cholesterol and coronary heart disease (CHD) is well established. Questions remain about the association between HDL cholesterol and stroke, particularly for stroke subtypes. METHODS AND RESULTS Cox survival models were applied to individual participant data from 25 cohort studies (about 80 000 subjects), with a median...

Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels are associated, respectively, with either increased risk or apparent protective effects for atherothrombosis. The ability of purified LDL and HDL to downregulate thrombin formation, a contributor to atherothrombotic processes, was assessed. Purified HDL, but not LDL, significantly enhanced inactivation of coagul...

HDL-cholesterol (HDL-C) values measured by precipitation (sodium phosphotungstate-MgCl2) and direct methods were compared with those obtained by HPLC with a new column (TSKgel Lipopropak) and an eluent (TSKeluent LP-1). The HDL-C values determined by the precipitation method were significantly (P <0.001) lower than those by the HPLC method, whereas the HDL-C values by the direct method were sli...