Structure versus activity studies deepening the identification of protein domains and the construction of biologically active recombinant peptides containing GSK2118436 purchase these domains are some of steps toward unraveling the real fungicidal/fungistatic potential of ureases and derived peptides. This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenadoria de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES), Fundação de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and Financiadora de Estudos e Projetos–FINEP. “
“Cardiac hypertrophy is characterized by myocardic tissue growth as
a consequence of an increase in cardiomyocyte protein synthesis and extracellular matrix deposition [2] and [12]. Cardiac see more remodeling follows several diseases including arterial hypertension and valve stenosis (pathological hypertrophy) or as the result of chronic exercise or pregnancy (physiological hypertrophy) [12]. Pathological cardiac hypertrophy is characterized by a thickening of the heart muscle which results in a decrease in the size of the heart chambers, including the left and right ventricles leading to diastolic dysfunction
and later to systolic dysfunction [2] and [12]. It is well established that the renin–angiotensin system (RAS) plays an important role in the progression of cardiac remodeling. The decrease in the overactivity of the angiotensin converting enzyme (ACE)/angiotensin (Ang) II/Ang II type 1 receptor (AT1) classical arm of RAS provides protection from pathological cardiac hypertrophy and subsequent heart failure [12] and [38]. Ang II, through its interactions with the AT1 receptor, has been demonstrated to increase fibroblast gene expression (including collagen), fibroblast density and proliferation, and myocyte hypertrophy, all of them
are hallmarks of myocardial fibrosis and remodeling [12] and [14]. On the other hand, ACE2 has been shown to have a high affinity to hydrolyse Ang II [16], the pressor, hypertrophic/profibrotic next hormone of the RAS, leading to the formation of Ang-(1–7), which presents vasodilator, anti-trophic and antifibrotic effects [6], [9], [13], [23] and [25]. Thus, a balance between the activities of these two arms of the RAS is important to keep cardiovascular homeostasis. It has been well documented in the heart that Ang-(1–7) presents several actions that oppose those of Ang II [36], [38], [39] and [40]. Most of the Ang-(1–7) actions are mediated by the Mas receptor [41], which is present in the heart and have an important role improving heart function in isolated-heart reperfusion technique [19], [37] and [39]. It was demonstrated that expression of an Ang-(1–7)-producing fusion protein produces cardioprotective effects in rats [39] and that chronic Mas-deficiency leads to impaired calcium handling in cardiomyocytes revealing a key role for the Ang-(1–7)/Mas axis as a modulator of cardiomyocyte function [13] and [23].