The Experts below are selected from a list of 8322 Experts worldwide ranked by ideXlab platform

Devanand B Shinde - One of the best experts on this subject based on the ideXlab platform.

Santosh N Mokale - One of the best experts on this subject based on the ideXlab platform.

Priyanka T Sanap - One of the best experts on this subject based on the ideXlab platform.

Ramesh Chandra - One of the best experts on this subject based on the ideXlab platform.

Robert W Mahley - One of the best experts on this subject based on the ideXlab platform.

  • pathogenesis of type iii hyperlipoproteinemia dysbetalipoproteinemia questions quandaries and paradoxes
    Journal of Lipid Research, 1999
    Co-Authors: Robert W Mahley, Yadong Huang, S C Rall
    Abstract:

    Type III hyperlipoproteinemia (HLP) is a genetic disorder characterized by accumulation of remnant lipoproteins in the plasma and development of premature atherosclerosis. Although receptor binding-defective forms of apolipoprotein (apo) E are the common denominator in this disorder, a number of apparent paradoxes concerning its pathogenesis still exist. However, studies in transgenic animals are resolving the mechanisms underlying this disorder. Paradox I: Defective apoE (commonly apoE2) is essential but not sufficient to cause overt type III HLP. In fact, most apoE2 homozygotes are Hypolipidemic. Studies in apoE2 transgenic models have demonstrated the impact of other genes or hormones in converting the hypolipidemia to hyperlipidemia. Paradox II: Among apoE2 homozygotes, men are more susceptible than women to type III HLP. Transgenic studies have shown that estrogen affects both LDL receptor expression and lipolytic processing, explaining the resistance of women to this disorder until after menopause. Paradox III: ApoE deficiency is associated with hypercholesterolemia, whereas the type III HLP phenotype is characterized by both hypercholesterolemia and hypertriglyceridemia. The hypercholesterolemia is caused by impaired receptor-mediated clearance, whereas the hypertriglyceridemia is caused primarily by impaired lipolytic processing of remnants and increased VLDL production associated with increased levels of apoE. Paradox IV: ApoE2 is associated with recessive inheritance of this disorder, whereas other defective apoE variants are associated with dominant inheritance. Determinants of the mode of inheritance are the differential binding of apoE variants to the LDL receptor versus the HSPG/LRP complex and the preference of certain apoE variants for specific lipoproteins. Thus, the pathogenesis of this sometimes mysterious disorder has been clarified.—Mahley, R. W., Y. Huang, and S. C. Rall, Jr. Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia): questions, quandaries, and paradoxes. J. Lipid Res. 1999. 40: 1933–1949.

  • genetic factors precipitating type iii hyperlipoproteinemia in Hypolipidemic transgenic mice expressing human apolipoprotein e2
    Arteriosclerosis Thrombosis and Vascular Biology, 1997
    Co-Authors: Yadong Huang, S C Rall, Robert W Mahley
    Abstract:

    Several factors are hypothesized to precipitate or exacerbate type III hyperlipoproteinemia (HLP) in humans. Among such factors are those that directly overload remnant lipoprotein production or disrupt removal pathways, including an increased ratio of apolipoprotein (apo) E2 to normal apoE, overproduction of apoB-containing lipoproteins, and decreased LDL receptor activity. Hypolipidemic apoE2-transgenic mice bred onto an apoE-null background had dramatically higher plasma total cholesterol (192 +/- 26 mg/dL for males, 203 +/- 40 mg/dL for females) and triglyceride (295 +/- 51 mg/dL for males, 277 +/- 58 mg/dL for females) levels than apoE2 mice with endogenous mouse apoE. Thus, eliminating normal apoE in the presence of apoE2 (thereby increasing the relative abundance of the defective ligand) can convert a Hypolipidemic to a hyperlipidemic phenotype. Hypolipidemic apoE2 transgenic mice overexpressing human apoB had moderate remnant accumulation compared with apoE2-only or apoB-only transgenic mice, indicating that overproduction of apoB-containing lipoproteins in the presence of apoE2 can augment remnant production. Hypolipidemic apoE2 transgenic mice bred-onto an LDL receptor-null background had markedly higher plasma total cholesterol (288 +/- 51 mg/dL for males, 298 +/- 73 mg/dL for females) and triglyceride (356 +/- 72 mg/dL for males, 317 +/- 88 mg/dL for females) levels than apoE2-only mice, and remnant accumulation increased even in apoE2 mice with a heterozygous LDL receptor-knockout background (compared with apoE2-only mice), suggesting that reducing or eliminating a major receptor-mediated remnant-removal pathway in the presence of apoE2 can also precipitate a hyperlipidemic phenotype. In all cases where either lipoprotein remnant production or removal pathways were severely stressed, increased remnant accumulation was apparent. As judged by the chemical characteristics of the remnant lipoproteins, the lipoprotein phenotype was quite similar to that of human type III HLP, especially in the apoE2-expressing mice with no endogenous apoE or LDL receptors, and thus these mice represent improved models of the disorder.