The Angiotensin-(1–12)/Chymase axis as an alternate component of the tissue renin angiotensin system

Ferrario, Carlos M.; Groban, Leanne; Wang, Hao; Cheng, Che Ping; VonCannon, Jessica L; Wright, Kendra N.; Sun, Xuming; Ahmad, Sarfaraz

doi:10.1016/j.mce.2020.111119

Cited by 18 publications

(32 citation statements)

References 111 publications

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“…Transferring proteins and lipids locally and systemically to other organs is a fundamental function of EVs 35 . Our earlier demonstration of human EV chymase incorporation into rat’s cardiomyocytes evidence that circulating exosomes may constitute a vehicle for the transport of chymase into organs that express angiotensinogen and Ang-(1‒12) such as the heart, the kidneys, and even the thymus 13,18,52-54 .…”

Section: Discussionmentioning

confidence: 97%

Chymase in Plasma and Urine Extracellular Vesicles: Novel Biomarkers for Primary Hypertension

Ahmad,

Deep,

Punzi

et al. 2023

Preprint

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BACKGROUNDExtracellular vesicles (EVs) have emerged as a promising liquid biopsy for various diseases. For the first time, using plasma and urinary EVs, we assessed the activity of renin-angiotensin system (RAS), a central regulator of renal, cardiac, and vascular physiology, in patients with control (Group I) or uncontrolled (Group II) primary hypertension.METHODSEVs were isolated from 34 patients with history of hypertension, and characterized for size and concentration by nanoparticle tracking analyses, exosomal biomarkers by immunogold labeling coupled with transmission electron microscopy, flow cytometry and immunoblotting. EVs were analyzed for the hydrolytic activity of chymase, angiotensin converting enzyme (ACE), ACE2, and neprilysin (NEP) by HPLC.RESULTSPlasma and urinary EVs were enriched for small EVs and expressed exosomal markers (CD63, CD9, and CD81). The size of urinary EVs (but not plasma EVs) was significantly larger in Group II compared to Group I. Differential activity of RAS enzymes was observed, with significantly higher chymase activity compared to ACE, ACE2, and NEP in plasma EVs. Similarly, urinary EVs exhibited higher chymase and NEP activity compared to ACE and ACE2 activity. Importantly, compared to Group I, significantly higher chymase activity was observed in urinary EVs (p = 0.03) from Group II, while no significant difference in activity was observed for other RAS enzymes.CONCLUSIONSBioactive RAS enzymes are present in plasma and urinary EVs. Detecting chymase in plasma and urinary EVs uncovers a novel mechanism of angiotensin II-forming enzyme and could also mediate cell-cell communication and modulate signaling pathways in recipient cells.GRAPHICAL ABSTRACT

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Section: Discussionmentioning

confidence: 97%

Chymase in Plasma and Urine Extracellular Vesicles: Novel Biomarkers for Primary Hypertension

Ahmad,

Deep,

Punzi

et al. 2023

Preprint

Self Cite

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“…The central role of RAS is to maintain blood pressure and body fluid homeostasis [1]. The kidney is the main source of prorenin, the precursor of renin.…”

Section: The Renin-angiotensin-aldosterone Systemmentioning

confidence: 99%

“…Chronic inflammation is a hallmark of many AI diseases, and Ang II's pro-inflammatory effects may contribute to the development or progression of these conditions. Moreover, Ang II can stimulate the activation of immune cells, which are crucial in the immune responses [1]. This activation can induce the generation of pro-inflammatory molecules that contribute to the AI process.…”

Section: Introductionmentioning

confidence: 99%

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The Renin-Angiotensin System: The Challenge behind Autoimmune Dermatological Diseases

Maranduca,

Cosovanu,

Clim

et al. 2023

Diagnostics

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Autoimmune dermatological diseases (AIDD) encompass a diverse group of disorders characterized by aberrant immune responses targeting the skin and its associated structures. In recent years, emerging evidence suggests a potential involvement of the renin–angiotensin system (RAS) in the pathogenesis and progression of these conditions. RAS is a multicomponent cascade, primarily known for its role in regulating blood pressure and fluid balance. All of the RAS components play an important role in controlling inflammation and other immune responses. Angiotensin II, the main effector, acts on two essential receptors: Angiotensin Receptor 1 and 2 (AT1R and AT2R). A disturbance in the axis can lead to many pathological processes, including autoimmune (AI) diseases. AT1R activation triggers diverse signaling cascades involved in inflammation, fibrosis and tissue remodeling. Experimental studies have demonstrated the presence of AT1R in various cutaneous cells and immune cells, further emphasizing its potential contribution to the AI processes in the skin. Furthermore, recent investigations have highlighted the role of other RAS components, beyond angiotensin-converting enzyme (ACE) and Ang II, that may contribute to the pathophysiology of AIDD. Alternative pathways involving ACE2, Ang receptors and Ang-(1-7) have been implicated in regulating immune responses and tissue homeostasis within the skin microenvironment. Understanding the intricate involvement of the RAS in AIDD may provide novel therapeutic opportunities. Targeting specific components of the RAS, such as angiotensin receptor blockers (ARBs), ACE inhibitors (ACEIs) or alternative RAS pathway modulators, could potentially ameliorate inflammatory responses, reduce tissue damage and lessen disease manifestations. Further research is warranted to outline the exact mechanisms underlying RAS-mediated immune dysregulation in AIDD. This abstract aims to provide a concise overview of the intricate interplay between the RAS and AIDD. Therefore, we elaborate a systematic review of the potential challenge of RAS in the AIDD, including psoriasis, systemic sclerosis, vitiligo, lupus erythematosus and many more.

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“…The Mas receptor is reported to be present in the sarcolemma of cardiomyocytes (Bader et al, 2018 ). Chymase in mast cells localized to the heart represents renin and ACE independent pathway to AngII production (Ferrario et al, 2020 ; Froogh et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Heart Angiotensin-Converting Enzyme and Angiotensin-Converting Enzyme 2 Gene Expression Associated With Male Sex and Salt-Sensitive Hypertension in the Dahl Rat

et al. 2021

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Angiotensin-converting enzyme 2 (ACE 2) in the heart including its sex dependency in the hypertensive heart, has not been much studied compared to ACE. In the present study, we used the Dahl salt-sensitive rat exposed to fructose and salt to model a hypertensive phenotype in males, females, and ovariectomized females. Blood pressure was measured by the tale-cuff technique in the conscious state. Expression of RAS-related genes ACE, ACE2, angiotensin II receptor type 1, Mas1, and CMA1 in the heart were quantified. The results revealed small but significant differences between male and female groups. The main results indicate the presence of a male preponderance for an increase in ACE and ACE2 gene expression. The results are in accordance with the role of androgens or male chromosomal complement in controlling the expression of the two ACE genes.

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The Angiotensin-(1–12)/Chymase axis as an alternate component of the tissue renin angiotensin system

Cited by 18 publications

References 111 publications

Chymase in Plasma and Urine Extracellular Vesicles: Novel Biomarkers for Primary Hypertension

Chymase in Plasma and Urine Extracellular Vesicles: Novel Biomarkers for Primary Hypertension

The Renin-Angiotensin System: The Challenge behind Autoimmune Dermatological Diseases

Heart Angiotensin-Converting Enzyme and Angiotensin-Converting Enzyme 2 Gene Expression Associated With Male Sex and Salt-Sensitive Hypertension in the Dahl Rat

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