Search

Background: Abdominal aortic aneurysm (AAA) is a complex degenerative disease which leads to morbidity and mortality in a large portion of the elderly population. Current treatment options for AAA are quite limited as there is no proven indication for pharmacological therapy and surgery is recommended for AAA larger than 5·5 cm in luminal diameter. Thus there is a great need to elucidate the underlying pathophysiological cellular and molecular mechanisms to develop effective therapies. In this narrative review we will discuss recent findings concerning some potential molecular and clinical aspects of the renin angiotensin system (RAS) in AAA pathophysiology. Materials and methods: This narrative review is based on the material found on MEDLINE and PubMed up to April 2013. We looked for the terms 'angiotensin AT1 receptor ACE inhibitors' in combination with 'abdominal aortic aneurysm pathophysiology pathways'. Results: Several basic research and clinical studies have recently investigated the role of the RAS in AAA. In particular the subcutaneous infusion of Angiotensin II has been shown to induce AAA in Apo56 knockout mice. On the other hand the pharmacological treatments targeting this system have been shown as beneficial in AAA patients. Conclusions: Emerging evidence suggests that RAS may act as a molecular and therapeutic target for treating AAA. However several issues on the role of RAS and the protective activities of angiotensin converting enzyme (ACE) inhibitors and Angiotensin 1 receptors blockers against AAA require further clarifications. © 2013 Stichting European Society for Clinical Investigation Journal Foundation.

BackgroundCoronary atherothrombosis due to atherosclerotic plaque rupture or erosion is frequently associated with acute coronary syndromes (ACS). Significant efforts have been made to elucidate the pathophysiological mechanisms underlying acute coronary events. Materials and methodsThis narrative review is based on the material searched for and obtained via PubMed up to August 2014. The search terms we used were as follows: angiotensin, acute coronary syndromes, acute myocardial infarction' in combination with atherosclerosis, vulnerability, clinical trial, ACE inhibitors, inflammation'. ResultsAmong several regulatory components, the renin-angiotensin system (RAS) was shown as a key pathway modulating coronary atherosclerotic plaque vulnerability. Indeed, these molecules are involved in all stages of atherogenesis. Classically, the RAS is composed by a series of enzymatic reactions leading to the angiotensin (Ang) II generation and activity. However, the knowledge of RAS has expanded and become more complex. The discovery of novel components and their functions has revealed additional pathways that contribute to or counterbalance the actions of Ang II. In this review, we discussed on recent findings concerning the role of different angiotensin peptides in the pathophysiology of ACS and coronary atherothrombosis, exploring the link between these molecules and atherosclerotic plaque vulnerability. ConclusionsTreatments selectively targeting angiotensins (including Mas and AT2 agonists, ACE2 recombinant, or Ang-(1-7) and almandine in oral formulations) have been tested in animal studies or in small human subgroups, expanding the perspective in the ACS prevention. These novel strategies, especially in the counter-regulatory axis ACE2/Ang-(1-7)/Mas, might be promising to reduce plaque vulnerability and inflammation.

Despite many therapeutic advances leading to increasingly effective drug treatments, thrombotic events (such as ischaemic stroke, pulmonary embolism, deep venous thrombosis and acute myocardial infarction) still represent a major worldwide cause of morbidity and mortality. Remarkable effort has been made to identify new drug targets. There is growing evidence indicating that the recently described counter-regulator axis of the renin-angiotensin system (RAS), composed of Angiotensin-Converting Enzyme 2 (ACE2), Angiotensin-(1-7) and the Mas receptor, has protective effects against thrombosis. In addition, it could be considered as a promising target for treating or preventing this disease. In this narrative review, we focused on the recent findings of the role of the ACE2/Angiotensin-(1-7)/Mas axis on the haemostatic process and its therapeutic potential.

Recent data support the idea that the effects of RAS are not restricted to the cardiovascular and renal systems. Importantly, RAS modulates free radical production and the cellular synthesis of several molecules such as cytokines, chemokines and transcription factors. These functions reflect directly the RAS ability to modulate the cell growth, senescence and migration. Activation of the classic RAS, ACE/Ang II/AT(1)R, has been strictly related to down regulation of pro-survival genes (Nampt and Sirt3), increase in ROS production and pro-inflammatory cytokines and chemokines release, leading to cell senescence, inflammation and development of autoimmune dysfunctions. However, the new view of RAS, points to the ACE2/Ang-(1-7)/Mas receptor axis as a counter-regulator of the effects of the classic Ang II-mediated effects. This new pathway is not totally elucidated. However, some studies suggest an important role of this novel axis in the control of cytokines release as well as cell migration and synthesis, preventing extra-cellular matrix deposition and cell apoptosis. Classic RAS blockers have been proposed as anti-inflammatory and immunomodulatory agents and some studies suggest a new potential application of RAS blockers in autoimmune diseases. The aim of the present review is to update the novel roles of classical and new RAS components and their possible implication during the physiological aging, in the immune system and inflammation.