**Signaling Pathways of Cardiac Remodeling Related to Angiotensin II Signaling Pathways of Cardiac Remodeling Related to Angiotensin II**

Carolina Baraldi Araujo Restini, Arthur F. Engracia Garcia, Henrique Melo Natalin, Guilherme Melo Natalin and Elen Rizzi Arthur F. Engracia Garcia, Henrique Melo Natalin, Guilherme Melo Natalin and Elen Rizzi Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/66076

Carolina Baraldi Araujo Restini,

### **Abstract**

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50 Renin-Angiotensin System - Past, Present and Future

NEJMoa1208799

10.1056/NEJM200109203451215

Heart failure affects more than 23 million people worldwide, and its prognosis remains poor. Hypertension is one of the most prominent human health problem and places individuals at a higher risk for heart failure. Several factors interplay the development of hypertension contributing for decompensated heart hypertrophy. The reninangiotensin system (RAS) has been shown to be the foremost regulator of blood pressure. Many evidences have pointed out the importance of RAS and its key mediator, angiotensin II (Ang II), on signaling pathways involved in cardiac remodeling. The Ang II-induced hypertrophic effects seem to be related to increased reactive oxygen species (ROS). Under oxidative stress conditions, as those observed in hypertension and heart failure, the matrix metalloproteinases (MMP) is activated. Ang II is connected with TNFα and TGF-β by ROS-NF-κB-MMP mechanisms, which are involved in heart failure. The rationale of the present chapter is structured on the progression of heart failure related to Ang II, TNF-α and TGF-β by common signaling pathways. Pharmacotherapeutics approaches to the heart failure abound, but the mortality rates remain high. This chapter will also describe molecular mechanisms involved in heart failure highlighting that TGF-β and/or TNF-α inhibitors could contribute to treatment to this serious clinical condition.

**Keywords:** heart failure, renin-angiotensin system (RAS), hypertension, transforming growth factor-beta (TGF-β), tumor necrosis factor (TNF)-α, metalloproteinases (MMP)

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons
