Alternative pathways for angiotensin II generation in the cardiovascular system

Becari, Christiane; Oliveira, Eduardo B.; Salgado, Maria Cristina de Oliveira

doi:10.1590/s0100-879x2011007500093

Cited by 42 publications

(31 citation statements)

References 49 publications

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“…Different enzymes can form Ang II from Ang I: e.g. ACE1, tonin [49], trypsin [50], kallikrein [51], cathepsin G [52] and chymase [53-55]. ACE1 is present in many tissues as well as in biological fluids e.g.…”

Section: Renin-angiotensin Systemmentioning

confidence: 99%

“…Furthermore, Ang II can also activate angiotensin II type 2 receptors (AT2R) whose activities are thought to oppose those of AT1R [31, 42, 43]. AT2Rs are regarded as protective receptors as they may elicit vasodilatory, antihypertensive, proapoptotic as well as antiproliferative effects [53, 69] and as they can bind directly to AT1R thus inhibiting signaling through it [31]. ACE inhibitors are used as antihypertensive medications as they oppose the harmful effects of Ang II via AT1R by blocking the conversation of Ang I to Ang II by ACE1 thus elevating the levels of Ang(1-7) [42, 43].…”

Section: Renin-angiotensin Systemmentioning

confidence: 99%

“…This receptor has been found e.g. in eye, central nervous system, kidney, heart and brain [88, 90-93] and is known to act antagonistically to AT1R [53]. Due to its antiarrhythmogenic, antithrombogenic, growth-inhibitory and vasoconstrictive inhibitory properties, Ang(1-7) is seen as a protective peptide that acts as a counterregulator within RAS [38-40].…”

Section: Renin-angiotensin Systemmentioning

confidence: 99%

See 2 more Smart Citations

Many Faces of Renin-angiotensin System - Focus on Eye

Holappa¹,

Vapaatalo²,

Vaajanen³

2017

TOOPHTJ

126

110

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The renin-angiotensin system (RAS), that is known for its role in the regulation of blood pressure as well as in fluid and electrolyte homeostasis, comprises dozens of angiotensin peptides and peptidases and at least six receptors. Six central components constitute the two main axes of the RAS cascade. Angiotensin (1-7), an angiotensin converting enzyme 2 and Mas receptor axis (ACE2-Ang(1-7)-MasR) counterbalances the harmful effects of the angiotensin II, angiotensin converting enzyme 1 and angiotensin II type 1 receptor axis (ACE1-AngII-AT1R) Whereas systemic RAS is an important factor in blood pressure regulation, tissue-specific regulatory system, responsible for long term regional changes, that has been found in various organs. In other words, RAS is not only endocrine but also complicated autocrine system. The human eye has its own intraocular RAS that is present e.g. in the structures involved in aqueous humor dynamics. Local RAS may thus be a target in the development of new anti-glaucomatous drugs. In this review, we first describe the systemic RAS cascade and then the local ocular RAS especially in the anterior part of the eye.

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Section: Renin-angiotensin Systemmentioning

confidence: 99%

Section: Renin-angiotensin Systemmentioning

confidence: 99%

Section: Renin-angiotensin Systemmentioning

confidence: 99%

See 1 more Smart Citation

Many Faces of Renin-angiotensin System - Focus on Eye

Holappa¹,

Vapaatalo²,

Vaajanen³

2017

TOOPHTJ

126

110

View full text Add to dashboard Cite

show abstract

“…It has been known for some time that there are alternative pathways for converting Ang I to Ang II that do not require angiotensin converting enzyme (ACE). The accumulating evidence demonstrated the alternative Ang II-generating pathway through the enzyme mast cell chymase [29]. Mast cells synthesize renin and release during degranulation that can generate Ang II from Ang I [21, 30].…”

Section: Renin Angiotensin System and Mast Cellmentioning

confidence: 99%

Influence of Mast Cells in Drug-Induced Gingival Overgrowth

Subramani

Rathnavelu

Yeap

et al. 2013

Mediators of Inflammation

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Mast cells (MCs) are multifunctional effector cells that were originally thought to be involved in allergic disorders. Now it is known that they contain an array of mediators with a multitude of effects on many other cells. MCs have become a recent concern in drug-induced gingival overgrowth (DIGO), an unwanted outcome of systemic medication. Most of the studies have confirmed the significant presence of inflammation as a prerequisite for the overgrowth to occur. The inflammatory changes within the gingival tissue appear to influence the interaction between the inducing drug and the fibroblast activity. The development of antibodies to MC-specific enzymes, tryptase and chymase, has facilitated the study of mast cells in DIGO. Many immunohistochemical studies involving MCs have been conducted; as a result, DIGO tissues are found to have increased the number of MCs in the gingiva, especially in the area of fibrosis. At the cellular level, gingival fibrogenesis is initiated by several mediators which induce the recruitment of a large number of inflammatory cells, including MCs. The purpose of this paper is to access the roles played by MCs in gingival overgrowth to hypothesize a relationship between these highly specialized cells in the pathogenesis of DIGO.

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“…This enzyme is widely found in several organs such as lung, pancreas, liver, blood vessels (mesenteric and carotid arteries), heart and kidney of rodents 1,4,5 an d, at lower levels, in the rat prefrontal cortex 6 ) . The importance of this functional alternative pathway for Ang II generation was demonstrated in heart, carotid and mesenteric arteries from normotensive and spontaneously hypertensive (SHR) rats 7 . Also, ELA2 is a key player in ACE-independent dysregulation of the renin-angiotensin system in myocardial infarction and, possibly, other cardiovascular diseases 8 .…”

Section: Introductionmentioning

confidence: 99%

Elastase-2 knockout mice display anxiogenic‐ and antidepressant-like phenotype: putative role for BDNF metabolism in prefrontal cortex

Diniz

Ribeiro

Lesnikova

et al. 2017

Preprint

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Several pieces of evidence indicate that elastase-2 (ELA2; chymotrypsin-like ELA2) is an alternative pathway to the generation of angiotensin II (ANG II). Elastase-2 knockout mice (ELA2KO) exhibit alterations in the arterial blood pressure and heart rate. However, there is no data on the behavioral consequences of ELA2 deletion. In this study we addressed this question, submitting ELA2KO and wild-type (WT) mice to several models sensitive to anxiety-and depression-like, memory, and repetitive behaviors. Our data indicates a higher incidence of barbering behavior in ELA2KO compared to WT, as well as an anxiogenic phenotype, evaluated in the elevated plus maze (EPM). While a decrease in locomotor activity was observed in ELA2KO in EPM, this feature was not the main source of variation in the other parameters analyzed. The marble burying test (MBT) indicated increase in repetitive behavior, observed by a higher number of buried marbles. The actimeter test indicated a decrease in total activity and confirmed the increase in repetitive behavior. The spatial memory was tested by repeated exposure to the actimeter in a 24h interval. Both ELA2KO and WT exhibited decreased activity compared to the first exposure, without any distinction between the genotypes.However, when submitted to the cued fear conditioning, ELA2KO displayed lower levels of freezing behavior in the extinction session when compared to WT, but no difference was observed during the conditioning phase. Increased levels of BDNF were found in the prefrontal cortex but not in the hippocampus of ELA2KO mice compared to WT. Finally, in silico analysis indicates that ELA2 is putatively able to cleave BDNF, and incubation of the purified enzyme with BDNF led to the degradation of the later. Our data suggested an anxiogenic-and antidepressant-like phenotype of ELA2KO, possibly associated with increased levels of BDNF in the prefrontal cortex.

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Alternative pathways for angiotensin II generation in the cardiovascular system

Cited by 42 publications

References 49 publications

Many Faces of Renin-angiotensin System - Focus on Eye

Many Faces of Renin-angiotensin System - Focus on Eye

Influence of Mast Cells in Drug-Induced Gingival Overgrowth

Elastase-2 knockout mice display anxiogenic‐ and antidepressant-like phenotype: putative role for BDNF metabolism in prefrontal cortex

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