Increased LDL cholesterol and CRP in infants of mothers with type 1 diabetes.

Background: Proatherogenic stimuli during foetal life may predispose to development of atherosclerosis in adulthood. Elevated plasma low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP) expression is associated with increased risk of atherosclerosis.

Methods And Results: In this study, we examined how maternal type 1 diabetes affects foetal plasma LDL cholesterol and CRP.

Maternal diabetes causes coordinated down-regulation of genes involved with lipid metabolism in the murine fetal heart.

Maternal diabetes is associated with increased transport of lipids to the fetus and increased risk of hypertrophic cardiomyopathy in the fetus. During fetal life, the heart normally has limited capacity to use lipids as fuel; and, at least in adults, cardiac lipid accumulation may lead to cardiomyopathy. Postnatally, lipid supply is increased when the offspring begins to suckle.

Endothelial lipase is highly expressed in macrophages in advanced human atherosclerotic lesions.

Endothelial lipase (EL) is expressed in endothelial cells, and affects plasma lipoprotein metabolism by hydrolyzing phospholipids in HDL. To determine the cellular expression of EL mRNA and protein in human atherosclerotic lesions, we performed in situ hybridization and immunohistochemical studies on sections of carotid endarterectomy specimens from patients with symptomatic cerebrovascular disease. In each of eight patients, EL mRNA and/or protein were seen in areas between the necrotic core and the fibrotic cap where they colocalized with LPL and macrophage-specific CD68.

Placental triglyceride accumulation in maternal type 1 diabetes is associated with increased lipase gene expression.

Maternal diabetes can cause fetal macrosomia and increased risk of obesity, diabetes, and cardiovascular disease in adulthood of the offspring. Although increased transplacental lipid transport could be involved, the impact of maternal type 1 diabetes on molecular mechanisms for lipid transport in placenta is largely unknown. To examine whether maternal type 1 diabetes affects placental lipid metabolism, we measured lipids and mRNA expression of lipase-encoding genes in placentas from women with type 1 diabetes (n = 27) and a control group (n = 21).

Increased plasma pro-B-type natriuretic peptide in infants of women with type 1 diabetes.

Background: Up to 40% of newborn infants of women with type 1 diabetes have echocardiographic signs of cardiomyopathy. Increased plasma concentrations of B-type natriuretic peptide (BNP) and its precursor (proBNP) are markers of cardiac failure and hypoxia in adults. In this study, we investigated whether plasma concentrations of proBNP and/or BNP are increased in infants of women with type 1 diabetes.

Endothelial and lipoprotein lipases in human and mouse placenta.

Placenta expresses various lipase activities. However, a detailed characterization of the involved genes and proteins is lacking. In this study, we compared the expression of endothelial lipase (EL) and LPL in human term placenta.

Expression of the endothelial lipase gene in murine embryos and reproductive organs.

Endothelial lipase (EL) is a recently discovered member of the triglyceride-lipase family that is involved in plasma HDL metabolism. In this study, we investigated the putative role of EL in mouse reproduction by studying EL gene expression in mouse embryos and adult reproductive organs. PCR analysis revealed that EL mRNA is expressed in mouse embryos on embryonic day 8.

Human placenta secretes apolipoprotein B-100-containing lipoproteins.

Supply of lipids from the mother is essential for fetal growth and development. In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B-containing lipoproteins results in embryonic lethality. In humans, the yolk sac is vestigial.

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.