Preface

**Section 4 Miscellaneous Issues 107**

**VI** Contents

**and Uveitis 109**

Ozlem Sahin and Alireza Ziaei

**Reactive Oxygen Species 119**

Teixeira and Teresa Sousa

**Stem Cell Therapy 159**

**Outcome: A Review 201**

**Hepatic Diseases 215** Eylem Taskin and Celal Guven

**as Direct Renin Inhibitors 241** Anne Pihlanto and Sari Mäkinen

**the Brain 173**

Chapter 7 **The Role of Renin-Angiotensin System in Ocular Inflammation**

Chapter 8 **Regulation of the Renin-Angiotensin-Aldosterone System by**

Chapter 9 **Current Research of the Renin-Angiotensin System Effect on**

Chapter 10 **Renin-Angiotensin System MicroRNAs, Special Focus on**

Chapter 11 **Renin-Angiotensin System and Renal Allograft Long-Term**

Rosa M. Viero and Luis Gustavo Modelli de Andrade

Chapter 12 **Local Renin-Angiotensin System at Liver and Crosstalk with**

Chapter 13 **The Function of Renin and the Role of Food-Derived Peptides**

Manuela Morato, Marta Reina-Couto, Dora Pinho, António Albino-

Elham Ahmadian, Aziz Eftekhari and Ahmad Yari Khosroushahi

Jose Gerardo-Aviles, Shelley Allen and Patrick Gavin Kehoe

The renin-angiotensin system is a unique regulatory system by its nature and characteristic. Its main components have been discovered for the first time, in connection with blood pres‐ sure regulation. The historic pathway from Robert Tigerstedt and Gunnar Bergman to the discovery of the characteristics of individual elements and the study of their significance, including the first synthesis of the converting enzyme inhibitor, captopril, is described in the first chapter of the book by Otero-Losada et al. and José Milei. The accumulated data lead to qualitatively new knowledge of the whole system: local PAS (paracrine, autocrine, and inta‐ crine system), new metabolites (angiotensin III and angiotensin IV, angiotensin 1–7 and an‐ giotensin 1–9), new enzymes, and new receptors. In the second part of the book, the authors discuss the significance of the PAC for the functioning of the cardiovascular system. Restini et al. describe in detail the role of RAS main effector angiotensin II for the remodeling of the heart. A number of new studies, systematized by Kolakovic and Stankovic, clarify the im‐ portance of the two main types of angiotensin receptors in the pathophysiological mecha‐ nisms of atherosclerosis and interplay with other regulatory mechanisms. The importance of the first choice of antihypertensive therapy in the treatment of patients with chronic kidney disease is the focus of Georgianos et al. In the third part, the importance of PAC for the func‐ tioning of the reproductive system is described in the two separate chapters: the importance of classical and local PAS with the main effector angiotensin (1–7) for the development of pathological abnormalities in the progression of pregnancy (Pepin et al.) as well as the known facts about PAS and reproductive biology (by Castilho and colleagues). The fourth part contains chapters of varied content that systematize the latest facts in the respective topics. Morato et al. look at the new knowledge about the relationships between RAS and reactive oxygen species that are of great importance for a large number of disturbances. Newly discovered signal transduction pathways and their elements are also produced in the retina and are of great importance for the maintenance of the local homeostasis of the visual sensory system and for the control of the local inflammatory response (Ozlem). Ahmadian et al. systematize the interaction of stem cells and RAS as well as the importance of modula‐ tion of cellular interactions, including local RAS at different levels, which provides new per‐ spectives for stem cell therapy. MicroRNAs (miRNAs) are posttranscriptional gene expression regulators, which can remodel brain RAS and act as mediators between local and systemic RAS. Gerardo-Aviles et al., systematizing all of these facts, address the challenges of using miRNAs for diagnosis and therapeutic interventions in the future. Viero and de Andrade analyzed the effects of RAS blockade on the development of renal fibrosis and re‐ jection of allograft.

A new concept for a complete picture of the system is being created. From a system of blood pressure regulation, it becomes a complex system, extremely rich in feedback and regulating

both brain functions and functions of all internal organs. It could be called "äutonomic" en‐ docrine system. The central units of both autonomic systems converge on the level of the hypothalamus but interact not only on the central but also at the peripheral levels, making extremely precise regulation of body homeostasis.

**Anna Naidenova Tolekova**

Trakia University, Medical Faculty, Stara Zagora, Bulgaria

**Section 1**
