Maternal immunization affects in utero programming of insulin resistance and type 2 diabetes.

Maternal immunization with oxidized lipoproteins prior to pregnancy protects against atherogenic in utero programming by gestational hypercholesterolemia and enhances beneficial lymphocyte-dependent immune responses in offspring. To determine whether in utero programming and immunomodulation also affect insulin resistance (IR) and type 2 diabetes, we investigated the effects of immunization on glucose and insulin responses in LDL receptor-deficient mice fed regular or 60% sucrose diets, as well as in offspring fed 0.5% cholesterol or 60% sucrose diets.

Human oxidation-specific antibodies reduce foam cell formation and atherosclerosis progression.

Objectives: We sought to assess the in vivo importance of scavenger receptor (SR)-mediated uptake of oxidized low-density lipoprotein (OxLDL) in atherogenesis and to test the efficacy of human antibody IK17-Fab or IK17 single-chain Fv fragment (IK17-scFv), which lacks immunologic properties of intact antibodies other than the ability to inhibit uptake of OxLDL by macrophages, to inhibit atherosclerosis.

Background: The unregulated uptake of OxLDL by macrophage SR contributes to foam cell formation, but the importance of this pathway in vivo is uncertain.

Methods: Cholesterol-fed low-density lipoprotein receptor knockout (LDLR(-/-)) mice were treated with intraperitoneal infusion of human IK17-Fab (2.

Antisense oligonucleotide lowers plasma levels of apolipoprotein (a) and lipoprotein (a) in transgenic mice.

Objectives: This study sought to assess whether an antisense oligonucleotide (ASO) directed to apolipoprotein (a) [apo(a)] reduces apo(a) and lipoprotein (a) [Lp(a)] levels in transgenic mouse models.

Background: Elevated Lp(a) is a causal, independent, genetic risk factor for cardiovascular disease and myocardial infarction. Effective therapies to specifically lower plasma Lp(a) levels are lacking.

Antisense oligonucleotide directed to human apolipoprotein B-100 reduces lipoprotein(a) levels and oxidized phospholipids on human apolipoprotein B-100 particles in lipoprotein(a) transgenic mice.

Background: Lipoprotein (a) [Lp(a)] is a genetic cardiovascular risk factor that preferentially binds oxidized phospholipids (OxPL) in plasma. There is a lack of therapeutic agents that reduce plasma Lp(a) levels.

Methods And Results: Transgenic mice overexpressing human apolipoprotein B-100 (h-apoB-100 [h-apoB mice]) or h-apoB-100 plus human apo(a) to generate genuine Lp(a) particles [Lp(a) mice] were treated with the antisense oligonucleotide mipomersen directed to h-apoB-100 mRNA or control antisense oligonucleotide for 11 weeks by intraperitoneal injection.

A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma.

Oxidized phospholipids (OxPLs) on apolipoprotein B-100 (apoB-100) particles are strongly associated with lipoprotein [a] (Lp[a]). In this study, we evaluated whether Lp[a] is preferentially the carrier of OxPL in human plasma. The content of OxPL on apoB-100 particles was measured with monoclonal antibody E06, which recognizes the phosphocholine (PC) headgroup of oxidized but not native phospholipids.

Oxidized low-density lipoprotein biomarkers in patients with end-stage renal failure: acute effects of hemodialysis.

Objective: To assess the effect of end-stage renal failure on oxidized low-density lipoprotein (OxLDL) biomarkers and the acute effects of hemodialysis. Oxidized phospholipids (OxPL) on apolipoprotein B-100 (apoB) particles (OxPL/apoB) have been associated with cardiovascular disease and new cardiovascular events. Patients with end-stage renal failure have increased oxidative stress and are at significantly increased risk of cardiovascular disease.

Emerging approaches for imaging vulnerable plaques in patients.

The diagnosis of vulnerable plaques, which have the propensity to develop atherothrombosis, remains an elusive goal in clinical medicine. The most accepted features of vulnerable plaques, such as a large lipid core, increased inflammatory milieu and thin fibrous caps, have been well characterized through pathological studies. The ability to image a vulnerable plaque in susceptible patients would theoretically result in useful prognostic information that can be used to either monitor or treat patients at risk more aggressively.

Epicardial retinoid X receptor alpha is required for myocardial growth and coronary artery formation.

Vitamin A signals play critical roles during embryonic development. In particular, heart morphogenesis depends on vitamin A signals mediated by the retinoid X receptor alpha (RXRalpha), as the systemic mutation of this receptor results in thinning of the myocardium and embryonic lethality. However, the molecular and cellular mechanisms controlled by RXRalpha signaling in this process are unclear, because a myocardium-restricted RXRalpha mutation does not perturb heart morphogenesis.

Normal fate and altered function of the cardiac neural crest cell lineage in retinoic acid receptor mutant embryos.

Mouse embryos lacking the retinoic acid (RA) receptors RARalpha1 and RARbeta suffer from a failure to properly septate (divide) the early outflow tract of the heart into distinct aortic and pulmonary channels, a phenotype termed persistent truncus arteriosus. This phenotype is associated with a failure in the development of the cardiac neural crest cell lineage, which normally forms the aorticopulmonary septum. In this study, we examined the fate of the neural crest lineage in RARalpha1/RARbeta mutant embryos by crossing with the Wnt1-cre and conditional R26R alleles, which together constitute a genetic lineage marker for the neural crest.