Recent advances have improved our understanding of the renin‐angiotensin system (RAS). These have included the recognition that angiotensin (Ang)‐(1‐7) is a biologically active product of the RAS cascade. The identification of the ACE homologue ACE2, which forms Ang‐(1‐7) from Ang II, and the GPCR Mas as an Ang‐(1‐7) receptor have provided the necessary biochemical and molecular background and tools to study the biological significance of Ang‐(1‐7). Most available evidence supports a counter‐regulatory role for Ang‐(1‐7) by opposing many actions of Ang II on AT1 receptors, especially vasoconstriction and proliferation. Many studies have now shown that Ang‐(1‐7) by acting via Mas receptor exerts inhibitory effects on inflammation and on vascular and cellular growth mechanisms. Ang‐(1‐7) has also been shown to reduce key signalling pathways and molecules thought to be relevant for fibrogenesis. Here, we review recent findings related to the function of the ACE2/Ang‐(1‐7)/Mas axis and focus on the role of this axis in modifying processes associated with acute and chronic inflammation, including leukocyte influx, fibrogenesis and proliferation of certain cell types. More attention will be given to the involvement of the ACE2/Ang‐(1‐7)/Mas axis in the context of renal disease because of the known relevance of the RAS for the function of this organ and for the regulation of kidney inflammation and fibrosis. Taken together, this knowledge may help in paving the way for the development of novel treatments for chronic inflammatory and renal diseases.
In the past few years, there has been a growing interest in the heptapeptide Angiotensin(Ang)-(1-7), mainly because of its ability to counter regulate many of Ang II actions. Furthermore, heart and blood vessels are important target tissues for Ang-(1-7) formation and actions. The introduction of novel tools, such as the Ang-(1-7) antagonists, A-779 and D-pro7-Ang-(1-7), the Ang-(1-7) agonist AVE 0991, transgenic rats TGR(A-1-7)3292, and use of liposome-encapsulated Ang-(1-7) for evaluating the biochemical and functional role of Ang-(1-7), have produced a great impact in this field of research. Moreover, the recent identification of the Ang-(1-7)-forming enzyme ACE2 and of the Ang-(1-7) receptor Mas will allow important advances in our understanding of the physiological and pathological role of this peptide. In this review, we will discuss the current knowledge concerning the biological effects of Ang-(1-7) in the blood, heart, and blood vessels. In addition, we will highlight the possible applications of agonists of its receptor as therapeutic agents in cardiovascular and related diseases.
The blockade of AT1 receptor exerts anti-inflammatory and anti-osteoclastic effects, thus protecting periodontal tissues in distinct pathophysiological conditions of alveolar bone loss.
The aim of this study was to evaluate the effects of sodium hyaluronate (HY),
single-walled carbon nanotubes (SWCNTs) and HY-functionalized SWCNTs (HY-SWCNTs) on
the behavior of primary osteoblasts, as well as to investigate the deposition of
inorganic crystals on titanium surfaces coated with these biocomposites. Primary
osteoblasts were obtained from the calvarial bones of male newborn Wistar rats (5
rats for each cell extraction). We assessed cell viability using the
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay and by
double-staining with propidium iodide and Hoechst. We also assessed the formation of
mineralized bone nodules by von Kossa staining, the mRNA expression of bone repair
proteins, and the deposition of inorganic crystals on titanium surfaces coated with
HY, SWCNTs, or HY-SWCNTs. The results showed that treatment with these biocomposites
did not alter the viability of primary osteoblasts. Furthermore, deposition of
mineralized bone nodules was significantly increased by cells treated with HY and
HY-SWCNTs. This can be partly explained by an increase in the mRNA expression of type
I and III collagen, osteocalcin, and bone morphogenetic proteins 2 and 4.
Additionally, the titanium surface treated with HY-SWCNTs showed a significant
increase in the deposition of inorganic crystals. Thus, our data indicate that HY,
SWCNTs, and HY-SWCNTs are potentially useful for the development of new strategies
for bone tissue engineering.
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