Diversity of pathways for intracellular angiotensin II synthesis

Kumar, Rajesh; Boim, Mirian Aparecida

doi:10.1097/mnh.0b013e32831a9e20

Cited by 50 publications

(38 citation statements)

References 77 publications

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“…An enzyme inhibition study showed an involvement of renin and chymase, but not ACE, in intracellular angiotensin II synthesis, following exposure to high glucose (49). Some studies also demonstrated a significant contribution of chymase in cardiac angiotensin II generation (47,50,51).…”

Section: Local Rassmentioning

confidence: 99%

“…The site of the tissue angiotensin II generation, whether extracellular or intracellular, further determines angiotensin II-forming pathways. On the basis of the site of angiotensin II synthesis, the tissue RAS has been further categorized into the extracellular (autocrine/paracrine) and intracellular (intracrine) (47,48). An enzyme inhibition study showed an involvement of renin and chymase, but not ACE, in intracellular angiotensin II synthesis, following exposure to high glucose (49).…”

Section: Local Rassmentioning

confidence: 99%

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Renin^|^ndash;Angiotensin System, Hypertension, and Chronic Kidney Disease: Pharmacogenetic Implications

2012

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Abstract. About 80% of CKD (chronic kidney disease) patients are hypertensive, and kidney function and blood pressure are clearly related to both physiologic and pathologic conditions in a "vicious cycle". In this pathologic scenario, there is a renin-angiotensin system (RAS) hyperactivity associated to progression of renal damage. Current guidelines indicate as the first choice of antihypertensive intervention, the pharmacologic blockade of the RAS. Nonetheless, both response to treatment and renal protection have considerable inter-individual variability. The main aims of this review are to describe the genetic characteristics of RAS components and to identify the possible pharmacogenetic implications for RAS-blocker drugs in the hypertension-CKD scenario. To date, RAS polymorphisms have not been consistently associated to antihypertensive response and studies focusing on CKD are scarce. Nonetheless, pharmacogenetic studies for the RAS-blocker drugs could still be further explored, especially with new generation tools and focusing not only on the antihypertensive response, but also on renal protection as well.

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Section: Local Rassmentioning

confidence: 99%

Section: Local Rassmentioning

confidence: 99%

Renin^|^ndash;Angiotensin System, Hypertension, and Chronic Kidney Disease: Pharmacogenetic Implications

2012

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“…Interestingly, an alternative pathway was found for the synthesis of intracellular Ang Ⅱ in the presence of high glucose in vascular smooth muscle cells. Under normal glucose levels, Ang Ⅱ is generated by cathepsin D and ACE; however, Ang Ⅱ is obtained by cathepsin D and chymase action in the presence of high glucose [120,121] .…”

Section: Breaking Paradigmsmentioning

confidence: 99%

Renin-angiotensin system in the kidney: What is new?

Ferrão

Lara

Lowe

2014

WJN

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The renin-angiotensin system (RAS) has been known for more than a century as a cascade that regulates body fluid balance and blood pressure. Angiotensin Ⅱ (Ang Ⅱ) has many functions in different tissues; however it is on the kidney that this peptide exerts its main functions. New enzymes, alternative routes for Ang Ⅱ formation or even active Ang Ⅱ-derived peptides have now been described acting on Ang Ⅱ AT1 or AT2 receptors, or in receptors which have recently been cloned, such as Mas and AT4. Another interesting observation was that old members of the RAS, such as angiotensin converting enzyme (ACE), renin and prorenin, well known by its enzymatic activity, can also activate intracellular signaling pathways, acting as an outside-in signal transduction molecule or on the renin/(Pro)renin receptor. Moreover, the endocrine RAS, now is also known to have paracrine, autocrine and intracrine action on different tissues, expressing necessary components for local Ang Ⅱ formation. This in situ formation, especially in the kidney, increases Ang Ⅱ levels to regulate blood pressure and renal functions. These discoveries, such as the ACE2/Ang-(1-7)/Mas axis and its antangonistic effect rather than classical deleterious Ang Ⅱ effects, improves the development of new drugs for treating hypertension and cardiovascular diseases. Key words: Renin-angiotensin system; Angiotensin Ⅱ; Kidney; Hypertension treatment; Receptor Core tip: Activation of the angiotensin converting enzyme (ACE)/ Angiotensin Ⅱ (Ang Ⅱ)/AT1 axis leads to vasoconstriction, anti-diuresis, anti-natriuresis, release of aldosterone and anti-diuretic hormone, which can result in hypertension, renal and cardiovascular diseases. Inhibition of renin and ACE or blocking AT1 receptor is the most used therapies for heart failure and hypertension. Nevertheless, the discovery of local Ang Ⅱ synthesis, new Ang Ⅱ metabolites, receptors and axis of this system, makes possible the development of new drugs and strategies for renal and cardiovascular diseases treatment, such as activation of ACE2/Ang-(1-7)/ Mas axis, which presents opposite effects of AT1 activation by Ang Ⅱ.

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“…This system is characterized by the presence of a functionally active RAS within the cells that can intracellularly synthesize Ang II [19,25]. This means that Ang II is involved not only in an endocrine but also is a paracrine and an intracrine signaling system within tissues [26].…”

Section: Tissue and Intracellular Rasmentioning

confidence: 99%

Involvement of the Renin‐Angiotensin System in Atherosclerosis

Kolaković¹,

Živković²,

Stanković³

2017

Renin-Angiotensin System - Past, Present and Future

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The renin-angiotensin system (RAS) is a well known for its role in the regulation of the blood pressure (BP). Angiotensin II (Ang II), the main mediator of the RAS, may act either, as a systemic molecule or a locally produced factor. Within the vessel wall it has significant proinflammatory role by inducing the oxidative stress, secretion of inflammatory cytokines and adhesion molecules. Ang II could trigger proliferation of vascular smooth muscle cells (VSMC) and its migration to the outer layer of the vessel wall. It could induce the release of matrix metalloproteinase (MMPs), from human VSMC and thus increase susceptibility to rupture of atherosclerotic lesions. Binding of Ang II to AT1R/AT2R could have opposing actions in vascular injury. The ACE2/Ang (1-7)/Mas axis of the RAS also opposes the unfavourable actions of ACE/Ang II/ATR1 axis. Inhibition of RAS could reduce inflammation-associated processes in vasculature, independently of lowering BP. RAS is significantly modulated by the genes coding for this system. Certain genetic variants (SNPs) in the RAS genes have been denoted as the functional ones and have been associated with hypertension, cardiovascular phenotypes and atherosclerosis. Also, the genetic components of the RAS interfere with the regulators of gene expression by microRNAs (miRs).

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Diversity of pathways for intracellular angiotensin II synthesis

Cited by 50 publications

References 77 publications

Renin^|^ndash;Angiotensin System, Hypertension, and Chronic Kidney Disease: Pharmacogenetic Implications

Renin^|^ndash;Angiotensin System, Hypertension, and Chronic Kidney Disease: Pharmacogenetic Implications

Renin-angiotensin system in the kidney: What is new?

Involvement of the Renin‐Angiotensin System in Atherosclerosis

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