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Biomedical subjects

Lars B Nielsen

Publications and source records attributed to Lars B Nielsen.

24 records · Page 2Linked to original sources
PubMed2003

Cardiac lipid accumulation associated with diastolic dysfunction in obese mice.

Obesity may confer cardiac dysfunction due to lipid accumulation in cardiomyocytes. To test this idea, we examined whether obese ob/ob mice display heart lipid accumulation and cardiac dysfunction. Ob/ob mouse hearts had increased expression of genes mediating extracellular generation, transport across the myocyte cell membrane, intracellular transport, mitochondrial uptake, and beta-oxidation of fatty acids compared with ob/+ mice. Accordingly, ob/ob mouse hearts contained more triglyceride (6.8 +/- 0.4 vs. 2.3 +/- 0.4 microg/mg; P < 0.0005) than ob/+ mouse hearts. Histological examinations showed marked accumulation of neutral lipid droplets within cardiac myocytes but not increased deposition of collagen between myocytes in ob/ob compared with ob/+ mouse hearts. On echocardiography, the ratio of E to A transmitral flow velocities (an indicator of diastolic function) was 1.8 +/- 0.1 in ob/ob mice and 2.5 +/- 0.1 in ob/+ mice (P = 0.0001). In contrast, the indexes of systolic function and heart brain natriuretic peptide mRNA expression were only marginally affected and unaffected, respectively, in ob/ob compared with ob/+ mice. The results suggest that ob/ob mouse hearts have increased expression of cardiac gene products that stimulate myocyte fatty acid uptake and triglyceride storage and accumulate neutral lipids within the cardiac myocytes. The results also suggest that the cardiac lipid accumulation is paralleled by cardiac diastolic dysfunction in ob/ob mice.

Animals↗
PubMed2002

Microsomal triglyceride transfer protein gene expression and triglyceride accumulation in hypoxic human hearts.

OBJECTIVES: Cardiac myocytes secrete apolipoprotein (apo)B-containing lipoproteins. Their function may be the removal of triglycerides when beta-oxidation of fatty acids is decreased, eg, during hypoxia. To test this hypothesis, we examined heart biopsies from patients undergoing coronary artery bypass graft (CABG, n=13) or valve replacement (n=6) surgery. METHODS AND RESULTS: Ventricular microsomal triglyceride transfer protein (P=0.02) and apoB (P=0.04) mRNA levels were both approximately 2-fold higher in CABG compared with valve replacement patients. In CABG patients, ventricular microsomal triglyceride transfer protein mRNA levels were negatively associated with the triglyceride content in ventricular myocytes (r=-0.70; P=0.02) and with mRNA levels of sterol regulatory element binding protein-1 (r=-0.74; P=0.004). CONCLUSIONS: The results are compatible with the notion that cardiac lipoprotein production is increased in hypoxic human ventricle, possibly as a result of decreased sterol regulatory element binding protein-1 expression. This might attenuate accumulation of triglycerides in cardiac myocytes.

Aged↗
PubMed2002

Chamber-dependent expression of brain natriuretic peptide and its mRNA in normal and diabetic pig heart.

Brain natriuretic peptide (BNP) is produced in cardiac myocytes, and increased secretion is closely associated with cardiac dysfunction. However, several fundamental aspects of BNP expression in the myocardium have not yet been resolved. In the present study, we report the presence of a precursor BNP mRNA transcript and a mature BNP mRNA transcript in normal porcine hearts. In normal pigs, the amount of precursor BNP mRNA was similar in atrial and ventricular myocardium, whereas the mature BNP transcript was 10- to 50-fold more abundant in atrial than in ventricular myocardium. Quantitation of proBNP in normal porcine hearts by radioimmunoassay disclosed abundant proBNP in the atria, whereas proBNP was undetectable in the ventricles. Laser confocal microscopy revealed proBNP in secretory granules of atrial but not in the ventricular myocardium of normal pigs. Mild streptozotocin-induced diabetes doubled the expression of BNP mRNA in porcine atrial myocardium (P=0.03), but was without effect on BNP mRNA in the ventricular myocardium. The data suggest that BNP mRNA processing and proBNP storage differ between the atrial and ventricular myocardium. The results also imply that diabetes increases cardiac BNP expression in a chamber-dependent manner.

Animals↗
PubMed2002

Hepatic expression of microsomal triglyceride transfer protein and in vivo secretion of triglyceride-rich lipoproteins are increased in obese diabetic mice.

Secondary hyperlipidemia is a major cardiovascular risk factor in individuals with type 2 diabetes. Increased hepatic production of apolipoprotein B (apoB)-containing lipoproteins contributes to the elevated plasma levels, but the mechanism is poorly understood. Recent results have established that microsomal triglyceride transfer protein (MTP) is rate limiting for the assembly and secretion of apoB-containing lipoproteins. To better understand the mechanism of type 2 diabetes-associated hyperlipidemia, we quantified hepatic MTP mRNA levels, hepatic microsomal triglyceride transfer activity, and in vivo triglyceride secretion from the liver in two diabetic mouse models. Obese diabetic (ob/ob) mice had 45% higher (P = 0.006) hepatic MTP mRNA levels, 54% higher (P < 0.0001) microsomal triglyceride transfer activity, and 70% higher (P < 0.0001) in vivo triglyceride secretion rates compared with ob/+ control mice. In contrast, in lean streptozotocin-treated diabetic mice, hepatic MTP mRNA levels were unchanged, whereas microsomal triglyceride transfer activity and in vivo triglyceride secretion rates were marginally decreased. These studies suggest that obesity-induced type 2 diabetes in mice confers increases in hepatic MTP expression and secretion of triglyceride-rich lipoproteins. High blood glucose and altered hepatic expression of sterol regulatory element binding protein genes play a minor role in this diabetic response.

Animals↗
PubMed2002

Simple method for quantification of Bence Jones proteins.

BACKGROUND: Quantification of free monoclonal light chains in urine [Bence Jones proteins (BJPs)] is used to diagnose multiple myeloma and to evaluate response to treatment. We have developed and evaluated an optimized approach for quantification of BJPs. METHODS: High-resolution gel electrophoresis of unconcentrated urine and albumin calibrators was carried out on Sebia's Hydrasys instrument with Hydragel HR agarose gels. After staining with acid violet, the gels were scanned densitometrically. The staining intensities of BJP bands relative to the staining intensities of albumin solutions were used to determine the BJP concentrations. Results for patient samples were compared with conventional agarose gel electrophoresis on concentrated samples. RESULTS: The relationships between staining intensity and the protein concentrations of albumin and BJPs were linear up to protein concentrations of approximately 2000 mg/L. The detection limit was approximately 20 mg/L. The interassay imprecision (CV) was approximately 8% (n = 23, duplicate analysis), and the results (y) showed a close positive relationship to the comparison method: slope = 0.82 (confidence interval, 0.75-0.88); y-intercept = 34 (-14 to 81) mg/L; n = 29; r(2) = 0.96. CONCLUSIONS: Agarose gel electrophoresis of unconcentrated urine samples together with a series of albumin calibrators followed by acid violet staining and densitometric scanning is sufficiently reproducible and sensitive to quantify clinically relevant BJPs.

Bence Jones Protein↗