Effect of antioxidants on modulation of lipoprotein lipase by alteration of heparan sulfate proteoglycans in endothelial cells

• Grant number: 19/03024-4
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2019
• End date: August 31, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Carina Mucciolo Melo
• Grantee: Carina Mucciolo Melo
• Host Institution: Centro Universitário FMABC (FMABC). Santo André , SP, Brazil
• Associated researchers: Maria Aparecida da Silva Pinhal

Abstract

Unbalance of serum lipid levels is a risk factor for cardiovascular and cerebrovascular diseases. Studies have shown that supplementation with 500mg / day vitamin C may improve dyslipidemia in adults and children, but the data are still controversial. The improvement of dyslipidemia may be related to the increase of syndecan-1 on the surface of the endothelium, since the treatment with this antioxidant can alter the degradation of this heparan sulfate proteoglycan. In mammals, four members have been described in the syndecan family; syndecan-1 appears to be related to the interaction of lipoproteins with lipoprotein lipase (LPL) and endothelium. LPL is a multifunctional enzyme that participates in the transport of lipids, whose function is the hydrolysis of triacylglycerol contained in chylomicron and very low-density lipoprotein (VLDL) lipoproteins. For the reasons presented, we are interested in analyzing whether the use of antioxidants decreases shedding of syndecan-1 endothelial cells and consequently alters the interaction of LPL with blood vessels. The assays will be performed using endothelial cell lineage as well as in vivo model using zebrafish. The lipid metabolism and transport of zebrafish are similar to that seen in humans, and the enzymes and apoproteins involved are conserved. The advantage of this animal model is that mating generates hundreds of embryos, which allows the use of a larger number of samples, substances can be administered in the swimming water and tests with confocal microscopy can be performed on intact and living embryos, which allows obtaining images of lipid transport in real time. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MELO, CARINA MUCCIOLO; WANG, HUAWEI; FUJIMURA, KEN; STRNADEL, JAN; MENEGHETTI, MARIA CECILIA ZOREL; NADER, HELENA BONCIANI; KLEMKE, RICHARD L.; PINHAL, MARIA APARECIDA SILVA. The Heparan Sulfate Binding Peptide in Tumor Progression of Triple-Negative Breast Cancer. FRONTIERS IN ONCOLOGY, v. 11, AUG 4 2021. (19/03024-4, 16/01357-8)