Regulation of hepatic high density lipoprotein binding proteins after administration of simvastatin and cholestyramine to rats.

Mathai, David S.; Fidge, Noel; Tozuka, Minoru; Mitchell, Amy M.

doi:10.1161/01.atv.10.6.1045

Cited by 17 publications

(5 citation statements)

References 26 publications

(11 reference statements)

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“…This suggests some association, either direct or indirect, between HB 2 and cholesterol metabolism. If, as expected, sterol synthesis was decreased in the cholesterolloaded cells, it would be consistent with a finding reported by this laboratory previously (23) that the administration of simvastatin to rats down-regulated HB 2 (and HB 1 ) expression by 50%. More studies are planned to investigate these relationships between HDL binding, HB 2 levels, and cell cholesterol metabolism.…”

Section: Fig 4 Expression Of Hb 2 In Monocytes and Macrophagessupporting

confidence: 92%

Cloning and Characterization of HB2, a Candidate High Density Lipoprotein Receptor

Matsumoto

Mitchell

Kurata

et al. 1997

Journal of Biological Chemistry

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The protection against coronary artery disease attributed to high density lipoprotein (HDL) may be associated with several functions, including its central role in reverse cholesterol transport, possible antioxidant and antithrombotic properties and others not yet identified which may depend on specific interactions between HDL and cell receptors. Several HDL-binding proteins have been identified including two candidate liver HDL receptors, HB 1 and HB 2 recently purified in this laboratory. We now report the cloning, sequencing, and some properties of HB 2 , the most abundant of the pair. It shows significant homology with the adhesion molecules ALCAM and BEN of the immunoglobulin superfamily and the cDNA, when transfected into HepG2 or COS cells, caused specific HDL 3 binding to increase by 80 -100%. Further, ligand blotting of glycoproteins isolated from phorbol 12-myristate 13-acetate-treated THP-1 cells or from transfected HepG2 and Chinese hamster ovary cells also provided evidence of increased binding of HDL 3 to HB 2 . Differentiation of THP-1 cells into macrophages resulted in a striking increase in HB 2 mRNA which was attenuated if cells were cholesterolloaded by incubation with acetylated low density lipoprotein. If the interaction between HDL and HB 2 reduces the adhesion-induced inflammatory cellular events that characterize arterial wall injury, thereby achieving the protection associated with higher plasma levels of HDL, these findings may provide a clue to one mitigating effect of HDL in heart disease.

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Section: Fig 4 Expression Of Hb 2 In Monocytes and Macrophagessupporting

confidence: 92%

Cloning and Characterization of HB2, a Candidate High Density Lipoprotein Receptor

Matsumoto

Mitchell

Kurata

et al. 1997

Journal of Biological Chemistry

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“…We previously reported the presence of two HDL-binding proteins (HB 1 and HB 2 ) in rat and human liver plasma membranes (5,6) and also showed that the expression of these candidate HDL-receptors could be reduced 50% by treating rats with the hyperlipidemic drug simvastatin (23). HB 2 levels could also be influenced by uploading macrophages with cholesterol (16), suggesting that this adhesion-type of HDL-binding protein may also be involved in cell lipid metabolism.…”

Section: Discussionmentioning

confidence: 98%

The identification of specific high density lipoprotein3 binding sites on human blood monocytes using fluorescence-labeled ligand

Hidaka

Tozuka

et al. 1999

Journal of Lipid Research

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We previously reported the identity and purification of two HDL 3 -binding proteins in rat liver plasma membranes. As these proteins are candidate high density lipoprotein (HDL) receptors and probably multifunctional, including a role in HDL metabolism, we have considerable interest in identifying corresponding proteins that are present in human tissue. This report describes the identification of HDL 3 -binding sites on human monocytes with the use of fluorescence microscopy and flow cytometry assay. After the incubation of mononuclear cells from human blood with fluorescein isothiocyanate (FITC)-labeled human HDL 3 , fluorescence micrographs showed dense signals of fluorescent grains on monocytes, but not lymphocytes. A significant increase in FITC intensity on monocytes, but not lymphocytes, was observed by flow cytometry analysis, and the interaction between FITC-HDL 3 and human monocytes was concentration-dependent. Although very low density (VLDL) and low density lipoprotein (LDL) were ineffective competitors and HDL 2 only partially competed for binding, a 50-fold concentration of HDL 3 did compete effectively for binding of FITC-HDL 3 to human monocytes. Trypsin treatment reduced the FITC intensity of monocytes, showing that a portion of cell-associated FITC-HDL 3 remained bound to the cell surface. Two major HDL-binding proteins were identified in CHAPS-solubilized human mononuclear cells by ligand blotting, using HDL 3 as the ligand. Both showed similar binding parameters, specificity, and molecular weight identical to HB 1 and HB 2 from rat liver plasma membrane. We conclude that corresponding candidate HDL receptors or a similar receptor complex also exist on human blood monocytes. -Hidaka, H., E. Hidaka, M. Tozuka, J. Nakayama, T. Katsuyama, and N. Fidge. Identification of specific high density lipoprotein 3 binding sites on human blood monocytes using fluorescence-labeled ligand.

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“…Oral bioavailability of simvastatin in rats was well established in previous studies. [38][39][40] Multiple subcutaneous injections of simvastatin administered in the week after fracture result in increased serum levels, cholesterol-lowering effects, and bone formation, but systemic levels and lipid-lowering effects decrease by 4 weeks. 41 The authors know of no study examining local simvastatin administration during tendon repair in rats, and systemic simvastatin levels are likely to be minimal at 4 and 8 weeks after repair.…”

Section: Limitationsmentioning

confidence: 99%

Simvastatin Exposure and Rotator Cuff Repair in a Rat Model

Deren¹,

Ehteshami²,

Dines³

et al. 2017

Orthopedics

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Simvastatin is a common medication prescribed for hypercholesterolemia that accelerates local bone formation. It is unclear whether simvastatin can accelerate healing at the tendon-bone interface after rotator cuff repair. This study was conducted to investigate whether local and systemic administration of simvastatin increased tendon-bone healing of the rotator cuff as detected by maximum load to failure in a controlled animal-based model. Supraspinatus tendon repair was performed on 120 Sprague-Dawley rats. Sixty rats had a polylactic acid membrane overlying the repair site. Of these, 30 contained simvastatin and 30 did not contain medication. Sixty rats underwent repair without a polylactic acid membrane. Of these, 30 received oral simvastatin (25 mg/kg/d) and 30 received a regular diet. At 4 weeks, 5 rats from each group were killed for histologic analysis. At 8 weeks, 5 rats from each group were killed for histologic analysis and the remaining 20 rats were killed for biomechanical analysis. One rat that received oral simvastatin died of muscle necrosis. Average maximum load to failure was 35.2±6.2 N for those receiving oral simvastatin, 36.8±9.0 N for oral control subjects, 39.5±12.8 N for those receiving local simvastatin, and 39.1±9.3 N for control subjects with a polylactic acid membrane. No statistically significant differences were found between any of the 4 groups (P>.05). Qualitative histologic findings showed that all groups showed increased collagen formation and organization at 8 weeks compared with 4 weeks, with no differences between the 4 groups at each time point. The use of systemic and local simvastatin offered no benefit over control groups. [Orthopedics. 2017; 40(2):e288-e292.].

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Regulation of hepatic high density lipoprotein binding proteins after administration of simvastatin and cholestyramine to rats.

Cited by 17 publications

References 26 publications

Cloning and Characterization of HB2, a Candidate High Density Lipoprotein Receptor

Cloning and Characterization of HB2, a Candidate High Density Lipoprotein Receptor

The identification of specific high density lipoprotein3 binding sites on human blood monocytes using fluorescence-labeled ligand

Simvastatin Exposure and Rotator Cuff Repair in a Rat Model

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