Increased local angiotensin II formation in aneurysmal aorta

Nishimoto, Masashi; Takai, Shinji; Fukumoto, Hitoshi; Tsunemi, Koutaro; Yuda, Atsushi; Sawada, Yoshihide; Yamada, Mayumi; Jin, Denan; Sakaguchi, Masato; Nishimoto, Yasuhisa; Sasaki, Satoshi; Miyazaki, Mizuo

doi:10.1016/s0024-3205(02)01998-7

Cited by 78 publications

(77 citation statements)

References 45 publications

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“…Ang induces promatrix metalloproteinase (proMMP)-9 expression 10) . Previous reports demonstrated that both chymase and total Ang -forming activities are significantly higher in aneurysmal aortae obtained from AAA patients than in normal aorta [11][12][13] . A study dealing with patients has shown that MMP-9 expression is associated with AAA progression through elastic fiber disruption 14) .…”

Section: Introductionmentioning

confidence: 89%

Involvement of Vascular Angiotensin II-Forming Enzymes in the Progression of Aortic Abdominal Aneurysms in Angiotensin II- Infused ApoE-Deficient Mice

Inoue

Muramatsu

Jin

et al. 2009

JAT

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Section: Introductionmentioning

confidence: 89%

Involvement of Vascular Angiotensin II-Forming Enzymes in the Progression of Aortic Abdominal Aneurysms in Angiotensin II- Infused ApoE-Deficient Mice

Inoue

Muramatsu

Jin

et al. 2009

JAT

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“…In angiotensin II-infused apoE-deficient mice, a significant expansion of aortic diameter was observed, along with significant augmentation of ACE, chymase, and MMP-9 activities in the aorta (20). With chymase inhibitor treatment, not only chymase activity but also MMP-9 activity was significantly attenuated, along with attenuation of AAA development (20).…”

Section: Effects Of Chymase Inhibitors In Abdominal Aortic Aneurysmmentioning

confidence: 97%

Multiple Mechanisms for the Action of Chymase Inhibitors

Jin

Miyazaki

2012

J Pharmacol Sci

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Abstract. Angiotensin II plays an important role in regulating blood pressure. Moreover, angiotensin II directly promotes organ damage by inducing expression of various genes, such as transforming growth factor (TGF)-β and matrix metalloproteinase (MMP)-9 precursors. Blockade of angiotensin II has been shown to not only lower blood pressure, but also to prevent cardiovascular and renal dysfunction and fibrosis. Inhibition of TGF-β and MMP-9 has also been shown to prevent cardiovascular and renal damage. A mast cell-produced enzyme, chymase, generates angiotensin II and also converts precursors of TGF-β and MMP-9 to their active forms. Chymase also strongly promotes accumulation of inflammatory cells. These multiple functions of chymase may play an important role in the development and promotion of various diseases. In fact, chymase inhibitors have been shown to prevent nonalcoholic steatohepatitis, intestinal inflammation, and adhesion formation after surgery and cardiovascular and renal damage. On the other hand, chymase inhibitors, unlike angiotensin-converting enzyme inhibitors and angiotensin II blockers, have no blood pressure-lowering effect despite blocking angiotensin II formation. Thus, chymase inhibitors may be useful for preventing damage to various organs via multiple mechanisms without lowering blood pressure.

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“…It has been reported that the ratio of chymase-dependent angiotensin II-forming activity to total angiotensin II-forming activity is significantly higher in aneurysmal aortas than in normal aortas (Ihara et al, 1999) [16,18]. It has also been reported that chymase activity was significantly increased in human AAA, and that accumulated chymase-positive mast cells were observed in the media and adventitia [19]. A specific chymase inhibitor, 2-(5-formyamino-6-oxo-2 phenyl-1, 6-dihydropyrmidine-1-yl) N-[{3, 4-dioxo-1-phenyl-7-} 2-pyridyloxy]}-2heptyl] acetamide (NK3201), has been shown to suppress the development of AAA in hamsters (Tsunemi et al, 2004) [16].…”

Section: Introductionmentioning

confidence: 98%

Effects of Angiotensin Receptor Blocker and Calcium Channel Blocker on Experimental Abdominal Aortic Aneurysms in a Hamster Model

Hosokawa

2010

Kurume Med. J.

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Summary:Remodeling in the abdominal aortic wall results in abdominal aortic aneurysm (AAA) formation. Many patients with AAA are prescribed antihypertensive drugs. However, the effects of antihypertensive drugs other than their effects on blood pressure control are rarely reported. In this study, we investigated the effects of these drugs on changes in the levels of matrix metalloproteinases (MMPs) and on AAA formation. Experimental AAAs were created in a hamster model by wrapping the abdominal aorta with elastase gauze. Olmesartan medoxomil (angiotensin II receptor antagonist) or azelnidipine (calcium channel antagonist) was administered to the hamsters and then we evaluated the aortic diameter, performed histological analysis, and analyzed the production of MMP-2 and MMP-9 by gelatin zymography. The expansion rate of the aortic diameter was smaller in both treatment groups than in the control group. Elastica van Gieson (EVG) staining showed structural preservation of elastin lamellae in both treatment groups. The active MMP-9 level decreased in both the olmesartan group and the azelnidipine group. Reducing MMP-9 production is important for suppression of AAA formation. Both olmesartan medoxomil and azelnidipine decreased MMP-9 activity, which suppressed degradation of the MMPs and inhibited AAA formation. There are different cascades that determine the production of MMP-9.Key words abdominal aortic aneurysm, matrix metalloproteinase-9, matrix metalloproteinase-2, angiotensin II receptor antagonist, olmesartan medoxomil

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Increased local angiotensin II formation in aneurysmal aorta

Cited by 78 publications

References 45 publications

Involvement of Vascular Angiotensin II-Forming Enzymes in the Progression of Aortic Abdominal Aneurysms in Angiotensin II- Infused ApoE-Deficient Mice

Involvement of Vascular Angiotensin II-Forming Enzymes in the Progression of Aortic Abdominal Aneurysms in Angiotensin II- Infused ApoE-Deficient Mice

Multiple Mechanisms for the Action of Chymase Inhibitors

Effects of Angiotensin Receptor Blocker and Calcium Channel Blocker on Experimental Abdominal Aortic Aneurysms in a Hamster Model

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