XCR1 conventional dendritic cell-induced CD4 T helper 1 cell activation exacerbates cardiac remodeling after ischemic myocardial injury.

Cardiac remodeling has no established therapies targeting inflammation. CD4 T-cell subsets have been reported to play significant roles in healing process after ischemic myocardial injury, but their detailed mechanisms of activation remain unknown. To explore immune reactions during cardiac remodeling, we applied a non-surgical model of coronary heart disease (CHD) induced by a high-fat diet (HFD-CHD) in SR-BI/ApoeR61 mice.

Rivaroxaban Suppresses the Progression of Ischemic Cardiomyopathy in a Murine Model of Diet-Induced Myocardial Infarction.

Aim: A direct oral anti-coagulant, FXa inhibitor, has been applied to the clinical treatment of myocardial infarction (MI). Experimental studies in mice indicated that FXa inhibitors reduced atherosclerosis and prevented cardiac dysfunction after coronary ligation. These studies suggested that protease-activated receptor (PAR) 2, a major receptor of activated FX, may play an important role in atherosclerosis and cardiac remodeling.

Widespread Coronary Dysfunction in the Absence of HDL Receptor SR-B1 in an Ischemic Cardiomyopathy Mouse Model.

Reduced clearance of lipoproteins by HDL scavenger receptor class B1 (SR-B1) plays an important role in occlusive coronary artery disease. However, it is not clear how much microvascular dysfunction contributes to ischemic cardiomyopathy. Our aim was to determine the distribution of vascular dysfunction in vivo in the coronary circulation of male mice after brief exposure to Paigen high fat diet, and whether this vasomotor dysfunction involved nitric oxide (NO) and or endothelium derived hyperpolarization factors (EDHF).

Myocardial energy provision is preserved by increased utilization of glucose and ketone bodies in CD36 knockout mice.

Aims: CD36 is an important transporter of long-chain fatty acids (LCFAs) in the myocardium. As we have reported previously, CD36-deficient patients demonstrate a marked reduction in myocardial uptake of (123)I-15-(p-iodophenyl)-(R, S)-methyl pentadecanoic acid (BMIPP), which is an analog of LCFAs, while myocardial (18)F-fluorodeoxy-glucose (FDG) uptake is increased. However, it has not been clarified whether energy provision is preserved in patients with CD36 deficiency.

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.

Effect of probucol on antioxidant properties of HDL in patients with heterozygous familial hypercholesterolemia.

Aim: High density lipoprotein (HDL) has multi-antiatherogenic effects such as antioxidation and anti-inflammation, in addition to being a key mediator of reverse cholesterol transport. Probucol, known as a lipid lowering drug, is also a potent antioxidant, but it decreases serum HDL cholesterol (HDL-C) levels. To elucidate the effect of probucol on antioxidant properties of HDL, we investigated the function of HDL derived from patients with heterozygous familial hypercholesterolemia (FH) who have been treated with probucol.

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.

Comprehensive expressional analyses of antisense transcripts in colon cancer tissues using artificial antisense probes.

Background: Recent studies have identified thousands of sense-antisense gene pairs across different genomes by computational mapping of cDNA sequences. These studies have shown that approximately 25% of all transcriptional units in the human and mouse genomes are involved in cis-sense-antisense pairs. However, the number of known sense-antisense pairs remains limited because currently available cDNA sequences represent only a fraction of the total number of transcripts comprising the transcriptome of each cell type.

Genome-wide analysis of expression modes and DNA methylation status at sense-antisense transcript loci in mouse.

The functionality of sense-antisense transcripts (SATs), although widespread throughout the mammalian genome, is largely unknown. Here, we analyzed the SATs expression and its associated promoter DNA methylation status by surveying 12 tissues of mice to gain insights into the relationship between expression and DNA methylation of SATs. We have found that sense and antisense expression positively correlate in most tissues.

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.

Pulmonary hypertension associated with bone marrow transplantation.

Bone marrow transplantation (BMT) is one of the promising methods of treatment of hematologic malignancy. However, it has a variety of complications since it involves fatal doses of anti-cancer drugs and radiation during the conditioning period. Among the various complications of BMT, pulmonary hypertension is rare and its pathogenesis is poorly understood.

H-InvDB in 2009: extended database and data mining resources for human genes and transcripts.

We report the extended database and data mining resources newly released in the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/).

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)].

Identification of novel endogenous antisense transcripts by DNA microarray analysis targeting complementary strand of annotated genes.

Background: Recent transcriptomic analyses in mammals have uncovered the widespread occurrence of endogenous antisense transcripts, termed natural antisense transcripts (NATs). NATs are transcribed from the opposite strand of the gene locus and are thought to control sense gene expression, but the mechanism of such regulation is as yet unknown. Although several thousand potential sense-antisense pairs have been identified in mammals, examples of functionally characterized NATs remain limited.

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.

Hyperlink Management System and ID Converter System: enabling maintenance-free hyperlinks among major biological databases.

Hyperlink Management System (HMS) is a system for automatically updating and maintaining hyperlinks among major public databases in the field of life science. We daily create corresponding tables of data IDs of major databases for human genes and proteins, and provide a CGI-program that returns correct and up-to-date URLs for showing data of various databases that correspond to user-specified IDs. The HMS can deal with various IDs: accession numbers of International Nucleotide Sequence Databases, HUGO Gene Symbols and IDs of UniProt, PDB, H-InvDB and others, and it can return URLs of various databases: H-InvDB, HUGO Gene Nomenclature Committee Database, NCBI Entrez Gene, UniProt, PDB and others.

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.

Comparative expression analysis uncovers novel features of endogenous antisense transcription.

Increasing numbers of sense-antisense transcripts (SATs), which are transcribed from the same chromosomal location but in opposite directions, have been identified in various eukaryotic species, but the biological meanings of most SATs remain unclear. To improve understanding of natural sense-antisense transcription, we performed comparative expression profiling of SATs conserved among humans and mice. Using custom oligo-arrays loaded with probes that represented SATs with both protein-coding and non-protein-coding transcripts, we showed that 33% of the 291 conserved SATs displayed identical expression patterns in the two species.