Hormonal systems in renal and cardiovascular diseases: from cell biology to new physiological paradigms with advances for therapeutics

Abstract

Cardiovascular and renal diseases are among the main "non-contagious pandemics" because they are responsible for exponential increase in morbidity and early mortality around the world. Common risk factors for cardiovascular and kidney diseases include: hypertension, diabetes, obesity and stress. Interestingly the participation of the renin angiotensin aldosterone system (RAS) has been evidenced in the pathophysiology of these various diseases, being a common point of modulation and/ or deregulation. RAS has extensive complexity, since it comprises several interconnecting and counterbalancing axes, its signaling profile permeates from autocrine and paracrine communication to endocrine and RAS interacts with several other hormonal systems essential to homeostasis, such as the kallikrein kinins system (KKS), prostaglandins and corticosteroids. Due to its wide complexity and importance in the pathophysiology of several diseases that converge on the main global causes of death from non-contagious diseases, RAS is a fertile field for research, especially in translating the results into clinical practice and public health policies. Based on the above, this thematic project aims to: evaluate the molecular mechanisms of cellular communication and the interactions of RAS components within and between systems against various treatments with RAS inhibitors and hormones; describe the modulation of RAS in response to potential new drugs, contemplating to elucidate the possible modulated mechanisms of action that may result in the desired pharmacological effect; to verify the role of the interaction of RAS with the KKS and with pro-renin and purinergic P2X7 receptors in the pathophysiology of cardiovascular, renal and obesity diseases; to evaluate how the RAS components are modulated in different pathophysiological states in order to identify prognostic and diagnostic biomarkers; and to investigate the response of RAS and its physiological effects in face of stressors and physical exercise. To this end, this thematic project will involve 19 challenges that are divided into three different research axes, the first axis corresponds to the study of the molecular mechanisms and interaction of RAS, the second axis is focused on the investigation of new drugs and biomarkers and the third has based on the investigation of RAS response to stress and exercise. The proposed challenges include basic and applied research, experimental models in cells and animals, and also population studies. Thus, the implementation of this thematic project will contribute to fill gaps in knowledge about the molecular and physiological mechanisms involving RAS and that are related to the development and progression of cardiovascular and renal diseases. Among the gains arising from the implementation of this project we can list: the identification of new therapeutic targets, the discovery of potential new drugs and biomarkers for diagnosis and prognosis, as well as a better understanding of the benefits of protective and prophylactic methods. Thus, consolidating knowledge for the development of new therapeutic approaches and public health policies, which benefit society as a whole. In addition to the contribution in the scientific and social sphere, it is important to highlight the contribution of this project in the formation of new researchers and scientific technical personnel, who will perpetuate the development and progress of national science. (AU)