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MicroRNAs are endogenous regulators of gene expression either by inhibiting translation or protein degradation. Recent studies indicate that microRNAs play a role in cardiovascular disease and renin-angiotensin-aldosterone system- (RAAS-) mediated cardiovascular inflammation, either as mediators or being targeted by RAAS pharmacological inhibitors. The exact role(s) of microRNAs in RAAS-mediated cardiovascular inflammation and remodeling is/are still in early stage of investigation. However, few microRNAs have been shown to play a role in RAAS signaling, particularly miR-155, miR-146a/b, miR-132/122, and miR-483-3p. Identification of specific microRNAs and their targets and elucidating microRNA-regulated mechanisms associated RAS-mediated cardiovascular inflammation and remodeling might lead to the development of novel pharmacological strategies to target RAAS-mediated vascular pathologies. This paper reviews microRNAs role in inflammatory factors mediating cardiovascular inflammation and RAAS genes and the effect of RAAS pharmacological inhibition on microRNAs and the resolution of RAAS-mediated cardiovascular inflammation and remodeling. Also, this paper discusses the advances on microRNAs-based therapeutic approaches that may be important in targeting RAAS signaling. [ABSTRACT FROM AUTHOR]

Many Studies suggest that changes in sympathetic nerve activity in the central nervous system might have a crucial role in blood pressure control. The present paper discusses evidence in support of the concept that the brain renin-angiotensin system (RAS) might be linked to sympathetic nerve activity in hypertension. The amount of neurotransmitter release from sympathetic nerve endings can be regulated by presynaptic receptors located on nerve terminals. It has been proposed that alterations in sympathetic nervous activity in the central nervous system of hypertension might be partially due to abnormalities in presynaptic modulation of neurotransmitter release. Recent evidence indicates that all components of the RAS have been identified in the brain. It has been proposed that the brain RAS may actively participate in the modulation of neurotransmitter release and influence the central sympathetic outflow to the periphery. This paper summarizes the results of studies to evaluate the possible relationship between the brain RAS and sympathetic neurotransmitter release in the central nervous system of hypertension. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction is found in hypertensive patients and may serve as a prognostic marker of future cardiovascular events. Endothelial function can be assessed noninvasively by flow-mediated vasodilation (FMD). The goal of this paper is to summarize comprehensively the clinical trials that investigated the effects of antihypertensive drugs on endothelial function assessed by FMD in hypertensive patients. A PubMed-based search found 38 clinical trial papers published from January 1999 to June 2011. Significant improvement of FMD after antihypertensive treatment was shown in 43 of 71 interventions (among 38 clinical trial papers). Angiotensin II receptor blockers and angiotensin converting enzyme inhibitors appeared to improve FMD more than other drug types. Antihypertensive treatment can improve endothelial dysfunction when assessed by FMD, although there are conflicting data that require further research. [ABSTRACT FROM AUTHOR]

In kidney transplantation, antibody-mediated allograft injury caused by donor HLA-specific antibodies (DSA) has recently been identified as one of the major causes of late graft loss. This paper gives a brief overview on the impact of DSA development on graft outcome in organ transplantation with a focus on risk factors for de novo alloantibody induction and recently published guidelines for monitoring of DSA during the posttransplant phase. [ABSTRACT FROM AUTHOR]

A complete renin-angiotensin system (RAS) is locally expressed in the brain and fulfills important functions. Angiotensin II, the major biologically active peptide of the RAS, acts via binding to two main receptor subtypes designated AT1 and AT2. The present paper focuses on AT2 receptors, which have been reported to have neuroprotective effects on stroke, degenerative diseases, and cognitive functions. Our group has identified a family of AT2 receptor interacting proteins (ATIPs) comprising three major members (ATIP1, ATIP3, and ATIP4) with different intracellular localization. Of interest, all ATIP members are expressed in brain tissues and carry a conserved domain able to interact with the AT2 receptor intracellular tail, suggesting a role in AT2-mediated brain functions. We summarize here current knowledge on the ATIP family of proteins, and we present new experimental evidence showing interaction defects between ATIP1 and two mutant forms of the AT2 receptor identified in cases of mental retardation. These studies point to a functional role of the AT2/ATIP1 axis in cognition. [ABSTRACT FROM AUTHOR]

Inflammation is recognized as an important factor in the pathophysiology of hypertension, with the renin-angiotensin-aldosterone system (RAAS) playing a key role in the disease. Initially described because of its contribution to extracellular fluid and electrolyte homeostasis, the RAAS has been implicated in endothelial dysfunction, vascular remodeling, oxidative stress, proinflammatory cytokine production, and adhesion molecule synthesis by the vascular wall. Both angiotensin II and aldosterone are involved in these systemic effects, activating innate and adaptive immune responses. This paper highlights some aspects connecting RAAS to the hypertensive phenotype, based on experimental and clinical studies, with emphasis on new findings regarding the contribution of an increasingly studied population of T lymphocytes: the T-regulatory lymphocytes. These cells can suppress inflammation and may exert beneficial vascular effects in animal models of hypertension. [ABSTRACT FROM AUTHOR]

The Renin-Angiotensin System(RAS) acts at multiple targets and has its synthesis machinery present in different tissues, including the heart. Actually, it is well known that besides Ang II, the RAS has other active peptides. Of particular interest is the heptapeptide Ang-(1-7) that has been shown to exert cardioprotective effects. In this way, great compilations about Ang-(1-7) actions in the heart have been presented in the literature. However, much less information is available concerning the Ang-(1-7) actions directly in cardiomyocytes. In this paper, we show the actual knowledge about Ang-(1-7)-mediated signaling in cardiac cells more specifically we provide a brief overview of ACE2/Ang-(1-7)/Mas axis; and highlight the discoveries made in cardiomyocyte physiology through the use of genetic approaches. Finally, we discuss the protective signaling induced by Ang-(1-7) in cardiomyocytes and point molecular determinants of these effects. [ABSTRACT FROM AUTHOR]

Angiotensin II (Ang II) is the main active product of the renin-angiotensin system (RAS), mediating its action via two major receptors, namely, the Ang II type 1 (AT1) receptor and the type 2 (AT2) receptor. Recent results also implicate several other members of the renin-angiotensin system in various aspects of brain functions. The first aim of this paper is to summarize the current state of knowledge regarding the properties and signaling of the AT2 receptor, its expression in the brain, and its wellestablished effects. Secondly, we will highlight the potential role of the AT2 receptor in cognitive function, neurological disorders and in the regulation of appetite and the possible link with development of metabolic disorders. The potential utility of novel nonpeptide selective AT2 receptor ligands in clarifying potential roles of this receptor in physiology will also be discussed. If confirmed, these new pharmacological tools should help to improve impaired cognitive performance, not only through its action on brainmicrocirculation and inflammation, but also through more specific effects on neurons. However, the overall physiological relevance of the AT2 receptor in the brain must also consider the Ang IV/AT4 receptor. [ABSTRACT FROM AUTHOR]

It is well known that the brain renin-angiotensin (RAS) system plays an essential role in the development of hypertension, mainly through the modulation of autonomic activities and vasopressin release. However, how the brain synthesizes angiotensin (Ang) II has been a debate for decades, largely due to the low renin activity. This paper first describes the expression of the vasoconstrictive arm of RAS components in the brain as well as their physiological and pathophysiological significance. It then focus on the (pro)renin receptor (PRR), a newly discovered component of the RAS which has a high level in the brain. We review the role of prorenin and PRR in peripheral organs and emphasize the involvement of brain PRR in the pathogenesis of hypertension. Some future perspectives in PRR research are heighted with respect to novel therapeutic target for the treatment of hypertension and other cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The intrarenal renin-angiotensin system (RAS) has several pathophysiologic functions not only in blood pressure regulation but also in the development of glomerulonephritis (GN). Angiotensin II (Ang II) is the biologically active product of the RAS. Locally produced Ang II induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation, regulates the gene expression of bioactive substances, and activates multiple intracellular signaling pathways, leading to tissue damage. Activation of the Ang II type 1 (AT1) receptor pathway results in the production of proinflammatory mediators, cell proliferation, and extracellular matrix synthesis, which facilitates glomerular injury. Previous studies have shown that angiotensin-converting enzyme inhibitors and/or AT1 receptor blockers have beneficial effects in experimental GN models and humans with various types of GN, and that these effects are more significant than their suppressive effects on blood pressure. In this paper, we focus on intrarenal RAS activation in the pathophysiology of experimental models of GN. [ABSTRACT FROM AUTHOR]