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  2. Research Institute
  3. Departments
  4. Department of Pathophysiology of Heart Failure and Therapeutics
  5. Molecular analysis of genes related to pathogenesis and pathophysiology of cardiovascular disease

Research Institute

Molecular analysis of genes related to pathogenesis and pathophysiology of cardiovascular disease

The first case of ARH (Autosomal recessive hypercholesterolemia) was analyzed and reported as having huge xanthomas and premature atherosclerosis like homozygous FH without any mutation in LDLR gene. Mutation in LDLRAP1, the adaptor protein of LDLR, was reported to show the symptom of FH. We have made a mouse that lacks LDLRAP1 and analyzed the phenotype. Mice that lack LDLRAP1 showed retardation of LDL metabolism in vivo, however their primary cultured hepatocytes showed normal function of LDL receptor. The functional analysis of LDLRAP1 is going on in our laboratory.

We also reported that a novel peptide, Neuromedin U (NMU), is involved in lipid metabolism and atherogenesis.

References

  1. Yuasa Y, Osaki T, Makino H, Iwamoto N, Kishimoto I, Usami M, Harada-Shiba M: Proeomic analysis of proteins eliminated by LDL-apheresis, Ther Apher Dial, in press
  2. Terasaki F, Morita H, Harada-Shiba M, Ohta N, Otsuka K, Nogi S, Miyamura M, Suzuki S, Ito T, Shimomura H, Katsumata T, Miyamoto Y, Ishizaka N: Familial Hypercholesterolemia with Multiple Large Tendinous Xanthomas and Advanced coronary Artery Atherosclerosis: Intern Med, 2013; 52: 577-581.
  3. Harada K, Miyamoto Y, Morisaki H, Ohta N, Yamanaka I, Kokubo Y, Makino H, Harada-Shiba M, Okayama A, Tomoike H, Okamura T, Saito Y, Yoshimasa Y, Morisaki T: A novel Thr56Met mutation of the autosomal recessive hypercholesterolemia gene associated with hypercholesterolemia. J Atheroscler Thromb, 2010; 17(2): 131-140.
  4. Harada-Shiba M, Takagi A, Marutsuka K, Moriguchi S, Yagyu H, Ishibashi S, Asada Y and Yokoyama S: Disruption of autosomal recessive hypercholesterolemia gene shows different phenotype in vitro and in vivo. Circ Res, 2004; 95:945-952.
  5. Harada-Shiba M, Takagi A, Miyamoto Y, Tsushima M, Ikeda Y, Yokoyama S and Yamamoto A: Clinical features and genetic analysis of autosomal recessive hypercholesterolemia. J Clin Endocrinol Metab, 2003; 88:2541-2547.
  6. Harada-Shiba M, Kinoshita M, Kamido H and Shimokado K: Oxidized low density lipoprotein induces apoptosis in cultured human umbilical vein endothelial cells by common and unique mechanisms. J Biol Chem, 1998; 273:9681-9687.
  7. Nishimura N, Harada-Shiba M, Tajima S, Sugano R, Yamamura T, Qiang QZ and Yamamoto A: Acquisition of secretion of transforming growth factor-beta 1 leads to autonomous suppression of scavenger receptor activity in a monocyte-macrophage cell line, THP-1. J Biol Chem, 1998; 273:1562-1567.

last updated：2022/06/27

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