Disease relevance of Vldlr

• These results demonstrate that there is downregulation of VLDL receptor gene expression in cardiac hypertrophy both in vivo and in vitro and suggest that the regulation of the VLDL receptor is possibly linked with the switch in energy substrate from lipid to glucose known to occur in cardiac hypertrophy [1].
• RNase protection assay showed that ventricular VLDL receptor mRNA falls to 41% of normal levels at 4 weeks when hypertension is not yet fully developed, and drops further to 14% at 13 weeks, when cardiac hypertrophy is established [1].
• In cultured neonatal rat ventricular cardiomyocytes, VLDL receptor mRNA decreases in parallel with the process of cardiocyte hypertrophy during the 24 hours after treatment with 10-8 mol/L endothelin-1, falling to 40% of the initial value [1].
• The CRF animals exhibited marked hypertriglyceridemia coupled with significant reductions in skeletal muscle and adipose tissue VLDL-R mRNA abundance and protein mass [2].
• VLDL-R protein was directly related to proteinuria and inversely related to plasma VLDL and triglyceride concentrations [3].

High impact information on Vldlr

• Reelin binding to apolipoprotein E receptor 2 (ApoER2) and very-low-density-lipoprotein receptor (VLDLR) leads to phosphorylation of disabled 1 (Dab1), an adaptor protein which associates with the intracellular domains of both receptors [4].
• Lipoprotein lipase mRNA decreases in parallel with VLDL receptor mRNA [1].
• These maneuvers did not affect VLDL receptor mRNA or protein levels in adipose tissue or heart [5].
• The physiological role of this putative VLDL receptor is not known, but its tissue distribution and ligand specificity suggest a possible role in the delivery of triglycerides to peripheral tissue [5].
• These studies suggest that the VLDL receptor plays a role in a metabolic process in muscle that is regulated by thyroid hormone [5].

Biological context of Vldlr

• In human and rat VLDLR, a variant form lacking 84 base pairs (bp) in O-linked sugar domain was noted but its significance was not initially understood [6].
• Down-regulation of VLDL-R expression, shown here for the first time, reveals another facet of disturbed lipid metabolism in CRF [7].
• 1. To elucidate the functional implication of very low density lipoprotein (VLDL) receptor, we studied the gene expression of VLDL receptor in rats [8].
• Proteins associated with cytoplasmic membrane functions (ACTN4, hyaluronan mediated motility receptor (RHAMM), VLDLR, GRK3) and/or endocytosis (DNM2) were also seen [9].

Anatomical context of Vldlr

• The tissue distribution of a variant VLDLR was detected in myelin as well as in other tissues except for the liver with immunohistochemistry using a monoclonal antibody [6].
• This was associated with an impressive fourfold reduction in heart and skeletal muscle VLDL-R mRNA and protein mass [7].
• The NS group showed a significant decline in VLDL-R protein (relative to total plasma membrane protein mass) in the heart and skeletal muscle paralleling the rise in plasma VLDL and triglyceride concentrations [3].
• In rat myoblast cells, serum deprivation for 24 h induced a reduction in VLDL-R proteins [10].
• Accordingly, cardiac tissue LPL activity, LPL and VLDL receptor proteins and mRNA abundance were studied in Sprague-Dawley rats 4 weeks after induction of severe thoracic aorta constriction or sham operation [11].

Associations of Vldlr with chemical compounds

• Based on these properties, VLDL-R is thought to play a role in VLDL and triglyceride metabolism [3].
• VLDL-R expression in heart and skeletal muscle were measured in rats with streptozotocin (STZ)-induced diabetes [10].
• In conclusion, puromycin-induced NS in rats is associated with profound reduction in heart and skeletal muscle VLDL receptor protein [3].
• VLDL-R mRNA levels in the heart and skeletal muscle were directly related to creatinine clearance and inversely related to serum triglyceride and VLDL concentrations [7].
• Use of specific pharmacologic inhibitors indicated that the tyrosine kinase inhibitors, herbimycin A and geldanamycin, completely reversed IL-1beta-induced downregulation of the VLDL receptor expression [12].

Other interactions of Vldlr

• Effect of diet on adipose tissue and skeletal muscle VLDL receptor and LPL: implications for obesity and hyperlipidemia [13].
• These cells express LDL receptor-related protein and the VLDL receptor, but not the LDL receptor [14].
• Insulin (10(-6) m), but not IGF-I (10 ng/ml), restored the decreased VLDL-R proteins by serum deprivation [10].
• In addition, the c-Src specific inhibitor PP2 or adenoviral-mediated gene transfer of kinase inactive (KI)-c-Src failed to reverse IL-1beta-induced downregulation of VLDL receptor expression [12].

Analytical, diagnostic and therapeutic context of Vldlr

• To this end, heart and skeletal muscle VLDL-R protein (Western blot) and mRNA (Northern blot) were measured at various points in the course of puromycin-induced NS in rats [3].
• To this end, VLDL-R mRNA (Northern blot) and protein mass (Western blot) of skeletal muscle (soleus) and heart were measured in male Sprague-Dawley rats six weeks after 5/6 nephrectomy (CRF group) or sham operation (NL group) [7].
• IL-1beta downregulated expression of the VLDL receptor in a time and dose-dependent manner as shown by Western blotting, Northern blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis [12].
• 2. We studied the gene expression of the VLDL receptor in the heart of stroke-prone spontaneously hypertensive rats (SHRSP), an animal model for hypertension-induced cardiac hypertrophy [8].

References