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Study of the biomechanical and histological properties of the abdominal aorta of diabetic rats and exposed to cigarette smoke

Grant number: 14/16725-7
Support type:Regular Research Grants
Duration: March 01, 2015 - February 28, 2017
Field of knowledge:Health Sciences - Medicine - Surgery
Principal researcher:Erasmo Simão da Silva
Grantee:Erasmo Simão da Silva
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Adriano Mesquita Alencar ; Ayumi Aurea Miyakawa Yamaguchi ; Felipe Trajano de Freitas Barão ; Hermes Vieira Barbeiro ; Silvia Lacchini

Abstract

Diseases affecting the segment of the abdominal aorta have high incidence and are associated with environmental and genetic risk factors. Among these conditions the infrarenal abdominal aortic aneurysm has important prevalence and is responsible for considerable mortality. Despite this, its pathogenesis is not completely defined. Positive association between smoking and aneurysm has been repeatedly confirmed, however, its association with diabetes is negative. This relationship considered unexpected since the aneurysm was traditionally attributed to atherosclerosis. Smokers have high proteolytic activity in the wall of the aorta, the result of an increase in local production of matrix metalloproteinases (MMP). This may be the cause of severe degradation of elastic fibers and consequent weakening of the arterial wall. In contrast, the diabetes is characterized by an increase in volume of the matrix that ultimately can reduce the risk of developing AAA. As aneurysms are an advanced morphological expression of the disease, the aim of this study is to determine in normal aortas, biomechanical and histological effects after exposure to cigarette smoke and development of diabetes mellitus in the rat aorta. For that will be studied 40 male Wistar rats weighing 300 to 350 g, 3 months old. These will be divided into four groups (10 animals per group): control, smoker, diabetic, smoker and diabetic. Smokers will be exposed to cigarette smoke for 16 weeks, 10 minutes a day the first week and 30 minutes in the remaining weeks, as passive smoking, according to Venturi system (300-400ppm), with cigarette containing 8% nicotine (Derby red-Souza Cruz). The diabetic animals will be produced by intravascular injection of streptozotocin (55mg/Kg). After sixteen weeks of the establishment of diabetes and early exposure to cigarette smoke, the animals will be sacrificed and samples of abdominal aorta will be carefully removed for destructive uniaxial biomechanical testing, histologic analysis, isolation and cultivation of vascular smooth muscle cells and zymography. This study aims to demonstrate that exposure to cigarette smoke and the diabetic state may affect the mechanical properties of the aorta and may also cause substantial structural changes in the arterial wall, especially in the middle layer. Indirectly, these findings may help to understand the role of these risk factors in AAA. (AU)

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