Modulation of vascular reactivity by visceral fat secretoma in distinct pathophysiological conditions: aging, menopause and hypercolesterolemia

• Grant number: 13/05440-9
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• Start date: June 29, 2013
• End date: September 28, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Maria Helena Catelli de Carvalho
• Grantee: Maria Helena Catelli de Carvalho
• Visiting researcher: Ana Paula Villela Dantas
• Visiting researcher institution: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Increase of abdominal fat has been appointed as an independent risk factor for cardiovascular disease. Many are the conditions in which fat mass is increased in the abdominal region, including high-fat diet, aging , menopause.In all cases, the augment of visceral fat is associated to chronic inflammation and increased cardiovascular risk. In spite of this, there is no direct evidence on how adipocyte metabolism modulates vascular inflammation and function, and even less is known on how adipocyte secretomes are regulated under the distinct pathophysiological conditionsAs part of a collaborative project with my group - with support from CAPES/DGU, Brazil and MECD, Espanha - Dra Ana Paula Dantas' group have found an aging-associated difference in the regulation of vascular function and morphology induced by high-fat diet. Moreover, preliminary results from ongoing experiments in Dr Dantas' lab reveal changes in global methylation status of visceral adipocytes in senescent and high-fat-diet fed animals that correlate with changes in inflammatory profile of fat cell secretome. In parallel, our group found that our model of menopause, i.e. ovariectomized spontaneous hypertensive rats (OVX SHR), also exhibits increase of abdominal fat in association with insulin resistance and impaired endothelial function in comparison to the their non-menopausal peer (SHR into physiological estrus). In this regard, we have hypothesized that the secretory products from abdominal fat in those three conditions (aging, high fat diet and menopause) contribute to the vascular damage observed in our animal models. To test our hypotheisis, Dr Dantas and my groups will sum-up efforts to set up a translational approach to determine vascular function in response to secretome of adipocyte cells. During her visit, Dr Dantas will kindly share her expertise in biomolecular methodologies to implement the techniques of primary adipocyte cell culture and secretome analysis. Our contribution to the project will consist in lend our expertise in vascular reactivity in the mesenteric circulation in vivo and in vitro to investigate vascular dysfunction and inflammation in response to components of secreted by visceral adipose tissue. For this, we will use an animal model of accelerated senescence (SAM mice) and one for metabolic syndrome induced by diet (SAM+ high-fat diet) and menopause (OVX SHR). These models arecurrently being used by the groups of Dr. Dantas, in Spain and my group at USP. During her stay at USP, Dr Dantas will also participate presenting a series of seminar on molecular regulation of vascular function in health, aging and disease in the PhD program of Pharmacology at our institute and in the under-graduation course in Biomedical Science at USP. Dr Dantas will also join our research team in a number of related activities including lab meetings to discuss scientific results, paper publication and the development of new research protocols. This three-month program will provide preliminary data that will lead to projects to increase our understanding of the mechanisms associated with secretory modifications by adipose tissue and their impact on cardiovascular health, which in the future will help to improve treatments and preventive measures of cardiovascular disease. (AU)