William J Cain

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Lipoprotein(a) (Lp[a]) is an atherogenic lipoprotein which is similar in structure to low density lipoproteins (LDL) but contains an additional protein called apolipoprotein(a) (apo[a]). Apo(a) is highly polymorphic in size, and there is a strong inverse association between the size of the apo(a) isoform and the plasma concentration of Lp(a). We directly(More)
Plasma levels of high density lipoprotein (HDL) cholesterol and its major protein component apolipoprotein (apo) A-I are significantly reduced in both acute and chronic inflammatory conditions, but the basis for this phenomenon is not well understood. We hypothesized that secretory phospholipase A(2) (sPLA(2)), an acute phase protein that has been found in(More)
The discovery of the ABCA1 lipid transporter has generated interest in modulating human plasma HDL levels and atherogenic risk by enhancing ABCA1 gene expression. To determine if increased ABCA1 expression modulates HDL metabolism in vivo, we generated transgenic mice that overexpress human ABCA1 (hABCA1-Tg). Hepatic and macrophage expression of hABCA1(More)
Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein which is similar in structure to, but metabolically distinct from, LDL. Factors regulating plasma concentrations of Lp(a) are poorly understood. Apo(a), the protein that distinguishes Lp(a) from LDL, is highly polymorphic, and apo(a) size is inversely correlated with plasma Lp(a) level. Even within the(More)
BACKGROUND Factors that regulate the metabolism of HDL and apolipoprotein A-I (apoA-I) are incompletely understood. Overexpression of endothelial lipase (EL) markedly reduces plasma levels of HDL cholesterol and apoA-I in mice, but the mechanisms of this effect remain unknown. METHODS AND RESULTS We used different doses of a recombinant adenoviral vector(More)
Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein which is similar in structure to low density lipoproteins (LDL). The role of the LDL receptor in the catabolism of Lp(a) has been controversial. We therefore investigated the in vivo catabolism of Lp(a) and LDL in five unrelated patients with homozygous familial hypercholesterolemia (FH) who have little(More)
The present study was undertaken to elucidate the metabolic basis for the increased remnants and lipoprotein(a) [Lp(a)] and decreased LDL apolipoprotein B (apoB) levels in human apoE deficiency. A primed constant infusion of (13)C(6)-phenylalanine was administered to a homozygous apoE-deficient subject. apoB-100 and apoB-48 were isolated, and tracer(More)
The cellular and molecular mechanisms responsible for lipoprotein [a] (Lp[a]) catabolism are unknown. We examined the plasma clearance of Lp[a] and LDL in mice using lipoproteins isolated from human plasma coupled to radiolabeled tyramine cellobiose. Lipoproteins were injected into wild-type, LDL receptor-deficient (Ldlr-/-), and apolipoprotein E-deficient(More)
Pancreatic islet beta-cells contain synaptic-like microvesicles (SLMVs). The origin, trafficking, and role of these SLMVs are poorly understood. In neurons, synaptic vesicle (SV) biogenesis is mediated by two different cytosolic adaptor protein complexes, a ubiquitous AP-2 complex and the neuron-specific AP-3B complex. Mice lacking AP-3B subunits exhibit(More)
Prox1 is a divergent homeodomain protein important for the development of the lens, retina, liver, pancreas, and lymphatic vasculature. Prox1 expression is highly upregulated in transformed hepatocytes and has been used as a marker to distinguish lymphatic from blood vasculature. We produced recombinant human Prox1 (amino acids 547-737) fused to glutathione(More)