The study of genetic and molecular profile of kallikrein-kinin system in familial hypercholesterolemia patients

• Grant number: 17/00719-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2017
• End date: January 31, 2019
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: João Bosco Pesquero
• Grantee: Clarissa Azevedo Bittencourt
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 14/27198-8 - Establishment of a center of genetic and molecular research for clinical challenges, AP.TEM

Abstract

Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by increased plasma levels of total cholesterol and low density lipoprotein cholesterol. FH is directly related with the development of cardiovascular diseases, such as hypertension, atherosclerosis, myocardial infarction and coronary disease. In this context, the kallikrein-kinin system (KKS) participates actively in the regulation of cardiovascular system functions, mainly through the action of bradykinin on directly release of nitric oxide (NO) in endothelium, as demonstrated by studies with angiotensin converting enzyme inhibitors. Genetic studies indicates that bradykinin B2 receptor gene polymorphisms affects the cardiac function by inducing ventricular hypertrophy, altering the efficiency of muscle contraction and increasing blood pressure. Others studies indicate that tecidual kallikrein polymorphisms are associated with the development of arterial dysfunction and hypertension. However, there are no studies that associate the participation of the KKS in patients with FH and its relation with cardiovascular events. Therefore, in this study we intend to investigate genetic alterations in majors KKS components, such as its enzymes and receptors, in patients with HF and its relation to development of cardiovascular diseases. Thereby, we intend to increase the knowledge of KKS's importance in these diseases and develop therapeutic strategies for patients with these genetic variations. (AU)