Establishment of a novel murine model of ischemic cardiomyopathy with multiple diffuse coronary lesions.

Objectives: Atherosclerotic lesions of the coronary arteries are the pathological basis for myocardial infarction and ischemic cardiomyopathy. Progression of heart failure after myocardial infarction is associated with cardiac remodeling, which has been studied by means of coronary ligation in mice. However, this ligation model requires excellent techniques.

Deletion of progranulin exacerbates atherosclerosis in ApoE knockout mice.

Aims: Progranulin (PGRN) is a multifunctional protein known to be involved in inflammation. However, the relation between PGRN and atherosclerosis remains elusive. The aim of this study was to define the role of PGRN in the development of atherosclerosis.

Apolipoprotein B-48 to triglyceride ratio is a novel and useful marker for detection of type III hyperlipidemia after antihyperlipidemic intervention.

Aim: Remnant lipoproteins are atherogenic and are accumulated in patients with type III hyperlipidemia (HL). Although type III HL is diagnosed by phenotyping apolipoprotein (apo) E, this procedure is time-consuming and inconvenient for routine clinical use. Clinical indices for screening type III HL in untreated HL patients have been proposed; however, in clinical settings, HL patients are promptly treated with lipid-lowering agents without diagnosing the underlying cause.

Serum adiponectin level is correlated with the size of HDL and LDL particles determined by high performance liquid chromatography.

Objective: Adiponectin (APN) improves insulin resistance and prevents atherosclerosis, and HDL removes cholesterol from atherosclerotic lesions. We have demonstrated that serum HDL-cholesterol (HDL-C) and APN concentrations are positively correlated and that APN accelerates reverse cholesterol transport (RCT) by increasing HDL synthesis in the liver and cholesterol efflux from macrophages. We previously reported that APN reduced apolipoprotein (apo) B secretion from the liver.

Patients with CD36 deficiency are associated with enhanced atherosclerotic cardiovascular diseases.

Aim: The clustering of dyslipidemia, impaired glucose tolerance and hypertension increases the morbidity and mortality from cardiovascular events. A class B scavenger receptor, CD36, is a receptor for oxidized LDL and a transporter of long-chain fatty acids. Because of the impaired uptake of oxidized LDL in CD36-deficient macrophages and from the results of CD36 knockout mice, CD36 deficiency (CD36-D) was supposed to be associated with reduced risks for coronary artery disease (CAD); however, CD36-D patients are often accompanied by a clustering of coronary risk factors.

Establishment of chemiluminescence enzyme immunoassay for apolipoprotein B-48 and its clinical applications for evaluation of impaired chylomicron remnant metabolism.

Background: Apolipoprotein B-48 (apoB-48) is a constituent of chylomicron remnants synthesized in the small intestines. The serum concentration of apoB-48 at fasting has been reported to be a marker of postprandial hyperlipidemia, a presumed risk factor for atherosclerosis.

Methods: We evaluated the basal performance of a recently developed chemiluminescent enzyme immunoassay (CLEIA).

Serum apolipoprotein B-48 levels are correlated with carotid intima-media thickness in subjects with normal serum triglyceride levels.

Background: Postprandial hyperlipidemia (PPHL) is an independent risk factor for coronary heart disease (CHD) which is based on the accumulation of chylomicrons (CM) and CM remnants containing apolipoprotein B-48 (apoB-48). Since atherosclerotic cardiovascular diseases are frequently observed even in subjects with normal serum triglyceride (TG) level, the correlation between fasting apoB-48 containing lipoproteins and carotid intima-media thickness (IMT) was analyzed in subjects with normal TG levels.

Methods: From subjects who took their annual health check at the Osaka Police Hospital (n=245, male), one-hundred and sixty-four male subjects were selected to take part in this study; the excluding factors were: systolic blood pressure ≥ 140 mmHg, intake of antihypertensive or antihyperlipidemic drugs, or age >65 years.

Molecular mechanisms of ezetimibe-induced attenuation of postprandial hypertriglyceridemia.

Aim: Postprandial hypertriglyceridemia (PHTG) has been shown repeatedly to be associated with metabolic syndrome and atherosclerotic cardiovascular diseases. We have recently reported that ezetimibe inhibits PHTG in patients with type IIb hyperlipidemia. Ezetimibe was also reported to atten-uate PHTG in combination with low-dose statins in patients with obesity or metabolic syndrome.

Fenofibrate reduces postprandial hypertriglyceridemia in CD36 knockout mice.

Aim: Metabolic syndrome (MetS) and postprandial hypertriglyceridemia (PHTG) are closely related and both are associated with coronary heart disease. We have demonstrated that CD36 deficiency is prevalent in the genetic background of MetS and is accompanied by PHTG concomitantly with an increase in remnants and a decrease in high density lipoprotein cholesterol. These findings make CD36 knockout mice (CD36KO) an interesting model for evaluating PHTG in MetS.

Differential reactivities of four homogeneous assays for LDL-cholesterol in serum to intermediate-density lipoproteins and small dense LDL: comparisons with the Friedewald equation.

Background: In routine clinical laboratory testing and numerous epidemiological studies, LDL-cholesterol (LDL-C) has been estimated commonly using the Friedewald equation. We investigated the relationship between the Friedewald equation and 4 homogeneous assays for LDL-C.

Methods: LDL-C was determined by 4 homogeneous assays [liquid selective detergent method: LDL-C (L), selective solubilization method: LDL-C (S), elimination method: LDL-C (E), and enzyme selective protecting method: LDL-C (P)].

Impaired insulin secretion in four Tangier disease patients with ABCA1 mutations.

Aim: Tangier disease (TD), caused by deficiency of ATP-binding cassette transporter A1, is characterized by the absence of high density lipoprotein and the accumulation of cholesteryl esters in many tissues. Recently, it has been reported that ABCA1 is expressed in pancreatic beta cells and mice with specific inactivation of ABCA1 in beta cells showed markedly impaired insulin secretion, suggesting that ABCA1 deficiency may be involved in diabetes. The aim of the current study was to confirm these findings by the oral glucose tolerance test (OGTT) in human subjects with ABCA1 deficiency.

Chylomicron remnants are increased in the postprandial state in CD36 deficiency.

The clustering of risk factors including dyslipidemia, hyperglycemia, and hypertension is highly atherogenic along with the excess of remnants from triglyceride (TG)-rich lipoproteins. CD36 is involved in the uptake of long-chain fatty acids (LCFAs) in muscles and small intestines. Patients with CD36 deficiency (CD36-D) have postprandial hypertriglyceridemia, insulin resistance, and hypertension.

Adiponectin prevents atherosclerosis by increasing cholesterol efflux from macrophages.

Plasma high density lipoprotein (HDL)-cholesterol levels are inversely correlated to the risk of atherosclerotic cardiovascular diseases. Reverse cholesterol transport (RCT) is one of the major protective systems against atherosclerosis, in which HDL particles play a crucial role to carry cholesterol derived from peripheral tissues to the liver. Recently, ATP-binding cassette transporters (ABCA1, ABCG1) and scavenger receptor (SR-BI) have been identified as important membrane receptors to generate HDL by removing cholesterol from foam cells.

Adiponectin deficiency suppresses ABCA1 expression and ApoA-I synthesis in the liver.

Plasma high density lipoprotein (HDL)-cholesterol levels are inversely correlated with the incidence of cardiovascular diseases. HDL is mainly assembled in the liver through the ATP-binding cassette transporter (ABCA1) pathway. In humans, plasma HDL-cholesterol levels are positively correlated with plasma adiponectin (APN) concentrations.

Adiponectin accelerates reverse cholesterol transport by increasing high density lipoprotein assembly in the liver.

Plasma high density lipoprotein (HDL)-cholesterol levels are negatively correlated with the incidence of coronary artery disease. HDL plays an important role in protecting against atherosclerosis by removing cholesterol from atheroma and transporting it back to the liver. The ATP-binding cassette transporters (ABCA1 and ABCG1) and scavenger receptor BI (SR-BI) are thought to be one of the rate-limiting factors to generate HDL in the liver.

Senescent phenotypes of skin fibroblasts from patients with Tangier disease.

Tangier disease (TD) is characterized by a deficiency of high density lipoprotein (HDL) in plasma and patients with TD have an increased risk for coronary artery disease (CAD). Recently, we reported that fibroblasts from TD exhibited large and flattened morphology, which is often observed in senescent cells. On the other hand, data have accumulated to show the relationship between cellular senescence and development of atherosclerotic CAD.