Effect of aerobic exercise training in plasma and arterial distribution and concentration of oxysterols in dyslipidemic mice

• Grant number: 14/07617-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2014
• End date: August 31, 2016
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Marisa Passarelli
• Grantee: Guilherme da Silva Ferreira
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Oxysterols are cholesterol oxidation derivatives that regulate the development of atherosclerosis by the selective modulation of oxidative stress and inflammation and by mediating arterial wall macrophage lipid exportation. Besides, oxysterols are bile acid precursors in the final step of cholesterol excretion into bile. 27 hydroxycholesterol is the most abundant oxysterol in circulation being transported by HDL mainly. Regular physical exercise improves reverse cholesterol transport promotting cholesterol removal from macrophages and its traffic to the liver that contributes to the reduction of atherosclerosis. Our hypothesis is that exercise training alters the concentration and distribution of oxysterol subespecies in plasma and arterial wall compartments in dyslipidemic mice leading to a better mobilization of arterial lipids by the reverse cholesterol transport. The objective of this study is to evaluate the concentration and distribution of oxysterols in plasma and aorta of apo E knockout mice submitted to aerobic exercise program. Animals will be randomly divided into sedentary and trained groups (treadmill; 15m/min, 30 min/day, 5 days/week, during 6 weeks). The concentration of total cholesterol, HDLcholesterol, tryglycerides and glucose will be determined by enzymatic methods and oxysterols (24S-hydroxycholesterol, 25-hydroxycholesterol, 27- hydroxycholesterol, 7-ketocholesterol, 7 beta-hydroxycholesterol) by gas chromatography coupled to mass spectrometry (GC-MS) after aorta and plasma lipid extraction. Total mRNA will be extracted from aorta for the mearument of Cyp27a and Cyp7b expressions by RT-PCR (that respectively generate and metabolize 27-hydroxycholesterol). Findings will be important for the comprehension of the mechanism by which physical exercise prevent and regress atherosclerosis and will indicate if the concentration of oxysterols can be a marker of these effects. (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)

FERREIRA, GUILHERME SILVA; PINTO, PAULA R.; IBORRA, RODRIGO T.; DEL BIANCO, VANESSA; MELLO SANTANA, MONIQUE FATIMA; NAKANDAKARE, EDNA REGINA; NUNES, VALERIA S.; NEGRAO, CARLOS E.; CATANOZI, SERGIO; PASSARELLI, MARISA. Aerobic Exercise Training Selectively Changes Oxysterol Levels and Metabolism Reducing Cholesterol Accumulation in the Aorta of Dyslipidemic Mice. FRONTIERS IN PHYSIOLOGY, v. 8, SEP 5 2017. (14/07617-6)

PINTO, PAULA R.; DA SILVA, KAROLLINE S.; IBORRA, RODRIGO T.; OKUDA, LIGIA S.; GOMES-KJERULF, DIEGO; FERREIRA, GUILHERME S.; MACHADO-LIMA, ADRIANA; ROCCO, DEBORA D. F. M.; NAKANDAKARE, EDNA R.; MACHADO, UBIRATAN F.; et al. Exercise Training Favorably Modulates Gene and Protein Expression That Regulate Arterial Cholesterol Content in CETP Transgenic Mice. FRONTIERS IN PHYSIOLOGY, v. 9, MAY 8 2018. (12/19112-0, 16/15603-0, 13/11084-0, 12/12088-7, 11/15153-1, 12/18724-2, 13/02854-7, 14/07617-6, 15/21072-5)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FERREIRA, Guilherme da Silva. Aerobic exercise training selectively changes oxysterol levels and metabolism reducing cholesterol accumulation in the aorta of dyslipidemic mice. 2017. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.