Differences in Tissue Angiotensin II–Forming Pathways by Species and Organs In Vitro

Akasu, Maki; Urata, Hidenori; Kinoshita, Akio; Sasaguri, Manabu; Ideishi, Munehito; Arakawa, Kikuo

doi:10.1161/01.hyp.32.3.514

Cited by 126 publications

(97 citation statements)

References 44 publications

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“…The extent of Ang II formation from Ang I was determined as described elsewhere, with some modifications. 21 The cells prepared as above were incubated with Ang I at 37 1C for 30 min. The amount of Ang II formed was analyzed by reversed-phase highperformance liquid chromatography (HPLC) using a C18 reversed-phase column (2.2Â25 cm; Vydac, Hesperia, CA, USA) with a 15-min linear acetonitrile gradient (3-13%) in 25 mmol l -1 triethylamine-phosphate buffer, pH 3, at a flow rate of 2 ml min -1 .…”

Section: Cell Culturementioning

confidence: 99%

Homocysteine-induced oxidative stress upregulates chymase in mouse mastocytoma cells

et al. 2009

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Reactive oxygen species (ROS) such as hydrogen peroxide (H 2 O 2 ), O À 2 and OH participate in the pathogenesis of ischemia/ reperfusion injury, inflammation and atherosclerosis. Our previous studies have suggested that increased angiotensin II (Ang II)-forming chymase may be involved in the development of atherosclerosis. However, the regulatory mechanism of chymase expression has not yet been clarified. In this study, we tested whether oxidative stress upregulates mouse mast cell proteinase chymase, mouse mast cell proteinase (MMCP)-5 or MMCP-4. We also examined the expression and activity of these proteins after treatment. Cultured mouse mastocytoma cells (MMC) displaying chymase-dependent Ang II-forming activity were treated with H 2 O 2 and several aminothiols with or without anti-oxidants. The levels of MMCP-5 and MMCP-4 expression were determined by quantitative RT-PCR; the level of chymase-dependent Ang II-forming activity was measured by high performance liquid chromatography using Ang I as a substrate. Treatment of MMC with homocysteine (0.1-3 mmol l -1 ) significantly increased MMCP-5 and MMCP-4 expression, as well as Ang II-forming activity. These effects were significantly inhibited by the addition of catalase and further suppressed by the combination of catalase and superoxide dismutase. Incubation with hydrogen peroxide alone caused a significant increase in Ang II-forming activity, which was completely suppressed by co-treatment with catalase. Furthermore, MMCP-5 and MMCP-4 expression levels were drastically suppressed and chymase induction by homocysteine was diminished under the GATA-inhibited condition. Homocysteine increased mast cell chymase expression and activity through the mechanism of oxidative stress. Our results suggest that there is a biochemical link between oxidative stress and the local Ang IIforming system.

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Section: Cell Culturementioning

confidence: 99%

Homocysteine-induced oxidative stress upregulates chymase in mouse mastocytoma cells

et al. 2009

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“…In vitro experiments with human 1,2 or animal heart extracts, 3,4 derived from either normal or failing hearts, have demonstrated unequivocally that the major Ang IIforming enzyme, responsible for 80% to 90% of the Ang II-forming capacity in the heart extracts, is chymase.…”

Section: See P 2555mentioning

confidence: 99%

Role For Chymase in Heart Failure

2003

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“…[17,18] Chymase-dependent angiotensin II formation has been reported to account for over 90% of total myocardial levels, although chymase levels do vary among species. [19] Chymase from human, dog, and hamster all hydrolyze the Phe 8 -His 9 bond of angiotensin I to efficiently produce angiotensin II. [20] In contrast, rodent chymase cleaves angiotensin I at the Tyr 4 -Ile 5 bond to generate inactive angiotensin fragments.…”

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ACE inhibitors to block MMP-9 activity: New functions for old inhibitors

Jin

Han

Lindsey

2007

Journal of Molecular and Cellular Cardiology

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Keywordsangiotensin converting enzyme inhibitors; matrix metalloproteinase-9; editorial Since the early 1990's, angiotensin converting enzyme (ACE) inhibitors have been used clinically to improve survival and reduce adverse left ventricular (LV) remodeling following myocardial infarction (MI). Seminal studies performed by the Pfeffer laboratory clearly demonstrated a survival benefit post-MI for both rats and humans treated with ACE inhibitors. [1,2] Several avenues of research have since sprouted to better understand the underlying mechanisms behind this benefit. Patten and colleagues demonstrated that both the ACE inhibitor enalapril and the angiotensin II type I receptor inhibitor losartan prevented LV hypertrophy and decreased collagen I gene expression compared to placebo-treated controls, suggesting that these events signaled through the angiotensin II type I receptor.[3] Yoshiyama and colleagues then showed that, in mice deficient for the angiotensin type I receptor, treatment with an ACE inhibitor prevented remodeling post-MI, indicating that ACE inhibitors also block angiotensin receptor-independent remodeling pathways. [4] In this issue, Dr. Yamamoto and colleagues examined the ability of the ACE inhibitor imidapril to directly bind to the matrix metalloproteinase MMP-9.[5] The importance of these findings is that ACE inhibition may also inhibit MMP-9, which provides a common link between strategies to prevent adverse remodeling post-MI (Figure 1). Adverse remodeling post-MI leading to congestive heart failure remains a leading cause of long-term morbidity and mortality. [6] ACE and MMP-9 are both zinc-dependent endopeptidases, both stimulate remodeling post-MI, and both process angiotensin I to form angiotensin II. [7] Matrix metalloproteinases are a family of 25 proteolytic enzymes defined by their ability to cleave individual extracellular matrix (ECM) components. MMP-9, also known as gelatinase B, processes multiple extracellular substrates, including denatured collagen I, fibronectin, and laminin.[8] Adding another layer of complexity, MMP-9 also cleaves non-ECM components, including cytokines and growth factors, to regulate multiple cell functions. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. to date, TIMP-1 binds MMP-9 with greatest affinity. NIH Public Access[10] MMPs have assigned roles in many cardiovascular diseases, including atherosclerosis, myocardial infarction, and heart failure [11]. Ample evidence has demonstrated a direct cause and effect relationship between MMP-9 and LV remodeling: 1) MMP-9 levels increase early post-MI [12], 2) MMP inhib...

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Differences in Tissue Angiotensin II–Forming Pathways by Species and Organs In Vitro

Cited by 126 publications

References 44 publications

Homocysteine-induced oxidative stress upregulates chymase in mouse mastocytoma cells

Homocysteine-induced oxidative stress upregulates chymase in mouse mastocytoma cells

Role For Chymase in Heart Failure

ACE inhibitors to block MMP-9 activity: New functions for old inhibitors

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