Cytogenetic and molecular diagnostic testing associated with prenatal and postnatal birth defects.

Genetic testing is beneficial for patients and providers when in search of answers to medical problems related to the prenatal or early postnatal period. It can help to identify the cause or confirm a diagnosis associated with developmental delay, intellectual disability, dysmorphic features, heart defects, multiple malformations, short stature, stillbirth, neonatal death, or fertility problems. Genetic testing can be used to rule out single-gene or chromosome abnormalities.

HDL from apoA1 transgenic mice expressing the 4WF isoform is resistant to oxidative loss of function.

HDL functions are impaired by myeloperoxidase (MPO), which selectively targets and oxidizes human apoA1. We previously found that the 4WF isoform of human apoA1, in which the four tryptophan residues are substituted with phenylalanine, is resistant to MPO-mediated loss of function. The purpose of this study was to generate 4WF apoA1 transgenic mice and compare functional properties of the 4WF and wild-type human apoA1 isoforms in vivo.

An abundant dysfunctional apolipoprotein A1 in human atheroma.

Recent studies have indicated that high-density lipoproteins (HDLs) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma are dysfunctional and are extensively oxidized by myeloperoxidase (MPO). In vitro oxidation of either apoA1 or HDL particles by MPO impairs their cholesterol acceptor function. Here, using phage display affinity maturation, we developed a high-affinity monoclonal antibody that specifically recognizes both apoA1 and HDL that have been modified by the MPO-H2O2-Cl(-) system.

Effects of native and myeloperoxidase-modified apolipoprotein a-I on reverse cholesterol transport and atherosclerosis in mice.

Objective: Preclinical and clinical studies have shown beneficial effects of infusions of apolipoprotein A-I (ApoA-I) on atherosclerosis. ApoA-I is also a target for myeloperoxidase-mediated oxidation, leading in vitro to a loss of its ability to promote ATP-binding cassette transporter A1-dependent macrophage cholesterol efflux. Therefore, we hypothesized that myeloperoxidase-mediated ApoA-I oxidation would impair its promotion of reverse cholesterol transport in vivo and the beneficial effects on atherosclerotic plaques.

Transcriptome analysis of genes regulated by cholesterol loading in two strains of mouse macrophages associates lysosome pathway and ER stress response with atherosclerosis susceptibility.

Cholesterol loaded macrophages in the arterial intima are the earliest histological evidence of atherosclerosis. Studies of mouse models of atherosclerosis have shown that the strain background can have a significant effect on lesion development. We have previously shown that DBA/2 ApoE(-/-) mice have aortic root lesions 10-fold larger than AKR ApoE(-/-) mice.

Red blood cells play a role in reverse cholesterol transport.

Objective: Reverse cholesterol transport (RCT) involves the removal of cholesterol from peripheral tissue for excretion in the feces. Here, we determined whether red blood cells (RBCs) can contribute to RCT.

Methods And Results: We performed a series of studies in apolipoprotein AI-deficient mice where the high-density lipoprotein-mediated pathway of RCT is greatly diminished.

Changes in whole blood gene expression in obese subjects with type 2 diabetes following bariatric surgery: a pilot study.

Background: A pilot study was performed in order to investigate the effects of bariatric surgery on whole blood gene expression profiles in obese subjects with type 2 diabetes.

Methodology/principal Findings: Whole blood from eleven obese subjects with type 2 diabetes was collected in PAXgene tubes prior to and 6-12 months after bariatric surgery. Total RNA was isolated, amplified, labeled and hybridized to Illumina gene expression microarrays.

Zymosan-mediated inflammation impairs in vivo reverse cholesterol transport.

Inflammation has been proposed to impair HDL function and reverse cholesterol transport (RCT). We investigated the effects of inflammation mediated by zymosan, a yeast glucan, on multiple steps along the RCT pathway in vivo and ex vivo. Acute inflammation with 70 mg/kg zymosan impaired RCT to plasma, liver, and feces similarly by 17-22% (P < 0.

Combining genome-wide data from humans and animal models of dyslipidemia and atherosclerosis.

Purpose Of Review: Comparative genomics allows researchers to combine genome-wide association data from humans with studies in animal models in order to assist in the identification of the genes and the genetic variants that modify susceptibility to dyslipidemia and atherosclerosis.

Recent Findings: Association and linkage studies in human and rodent species have been successful in identifying genetic loci associated with complex traits, but have been less robust in identifying and validating the responsible gene and/or genetic variants. Recent technological advancements have assisted in the development of comparative genomic approaches, which rely on the combination of human and rodent datasets and bioinformatics tools, followed by the narrowing of concordant loci and improved identification of candidate genes and genetic variants.