Mast cell chymase in pulmonary hypertension

Mitani, Yoshihide; Ueda, Makiko; Maruyama, Kazuo; Shimpo, Hideto; Kojima, Akiko; Matsumura, Masahiko; Aoki, Kazuaki; Sakurai, Minoru

doi:10.1136/thx.54.1.88

Cited by 51 publications

(44 citation statements)

References 9 publications

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“…These result in the secretion and participation of mast cell mediators in I. Kasacka et al inflammatory reac-tions, bronchial spasm and increased mucus secretion, edema and damage to the endothelium. The enlargement of mast cells around the vessels may be consistent with the results of studies on their role in angiogenesis, fibrousness and the reconstruction of pulmonary vessel structure in lung hypertension (Mitani et al, 1999). Biologically active substances released from mast cells have the ability of degrading numerous structural and enzymatic proteins, and glycosaminoglycans.…”

Section: Discussionsupporting

confidence: 84%

Morphometric evaluation of murine pulmonary mast cells in experimental hemorrhagic shock

Kasacka

Humenczyk-Zybala²,

Niczyporuk³

et al. 2009

Eur J Histochem

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Respiratory failure resulting frequently in death is one of the complications in the course of post-hemorrhagic changes. A systemic inflammatory reaction plays a significant role in the pathogenesis of this syndrome. Mast cells also contribute to this effect. To broaden our knowledge of the pathogenesis of respiratory insufficiency, we evaluated morphometrically lung mast cells in hemorrhagically shocked rats. Lung sections were stained with alcian blue and safranin, and four separate locations were distinguished: under the lung pleura, around the bronchi and the large vessels, and in the interalveolar septa. A decrease in the area and volume of mast cells and an increase in their circularity index in interalveolar septa and around the bronchi was observed. An enlargement of mast cells around lung vessels was also found. There were no changes in the morphometric parameters of mast cells under pleura. The results suggest an activation and degranulation of mast cells and a role in the inflammatory process causing acute lung injury in hemorrhagic shock.

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Section: Discussionsupporting

confidence: 84%

Morphometric evaluation of murine pulmonary mast cells in experimental hemorrhagic shock

Kasacka

Humenczyk-Zybala²,

Niczyporuk³

et al. 2009

Eur J Histochem

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“…Mast cell accumulation has been described in several types of PAH and an animal model. 68,69 Our group has recently identified an increase in c-kit-positive cells (including mast cells) in remodeled vessels and mobilization of bone marrow-derived circulating progenitor cells. 70 How mast cells may contribute to PAH pathophysiology is by guest on May 12, 2018 http://circ.ahajournals.org/ Downloaded from not clear, but proposed mechanisms include direct vasoactive effects and stimulation of remodeling by increased production of matrix metalloproteinases.…”

Section: Endothelial Dysfunction Perpetuates Altered Immune Responsesmentioning

confidence: 99%

Immune Dysregulation and Endothelial Dysfunction in Pulmonary Arterial Hypertension

et al. 2014

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“…Mitani et al (20) reported that the number of chymase-containing mast cells in lung vasculature was clearly increased in PH patients compared with non-PH patients. This finding suggests that chymase is involved in the pulmonary vascular remodeling of PH.…”

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confidence: 99%

Role of Chymase-Dependent Angiotensin II Formation in Monocrotaline-Induced Pulmonary Hypertensive Rats

et al. 2006

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Angiotensin II-forming chymase is expressed in the pulmonary arteries of the monocrotaline-induced pulmonary hypertensive rats, but its actual role is unclear. We studied chymasedependent angiotensin II formation in the pulmonary arteries of the monocrotaline-induced pulmonary hypertensive rats and observed the effects of an angiotensin II receptor blocker on vascular remodeling. Four weeks after the administration of monocrotaline (60 mg/kg, s.q.), echocardiographic, hemodynamic, morphometric and biochemical analyses were performed. Age-matched rats were used as controls. To evaluate the effects of an angiotensin II receptor blocker, 2 wk after beginning of monocrotaline treatment, the rats were given candesartan (10 mg/kg per day) or placebo for 2 wk. In the monocrotaline-induced pulmonary hypertensive rats, the elevated systolic pulmonary arterial pressure and right ventricular hypertrophy were observed. Medial hypertrophy of lung arterioles was also observed. Chymase activity and angiotensin II concentration, but not angiotensin-converting enzyme activity, were significantly increased in the lung. In the angiotensin II receptor blocker-treated group, both systolic pulmonary arterial pressure and right ventricular hypertrophy were significantly reduced, and arteriolar hypertrophy was also prevented. Thus, angiotensin II-forming chymase may play a role in the proliferation of the medial layer in the lung arterioles of monocrotaline-induced pulmonary hypertensive rats. C hymase is a chymotrypsin-like serine protease that is thought to be present in the secretory granules of mast cells. Chymase is able to cleave the bonds of angiotensin I between phenylalanine and histidine (1,2). Chymase purified from human cardiovascular tissues easily converts angiotensin I to angiotensin II (1,2), and chymase-dependent angiotensin II may have a role in human cardiovascular tissue function. For example, in human heart extracts, over 75% of total angiotensin II-forming activity depended on chymase, and the remaining depended on angiotensin-converting enzyme (ACE) (1). In human vascular tissue extracts, about 90% of total angiotensin II-forming activity was inhibited by a chymase inhibitor, and the remaining activity was inhibited by an ACE inhibitor (3). These findings suggest that chymase primarily produces angiotensin II compared with ACE in human cardiovascular tissues. However, both ACE inhibitor and angiotensin II receptor blocker (ARB) lower systemic blood pressure, suggesting that ACE plays a dominant role in regulating angiotensin II formation. Although chymase converts angiotensin I to angiotensin II in the extracts of hearts and arteries, chymase-dependent angiotensin II formation may be irrelevant for the regulation of blood pressure in vivo (4). Chymase is synthesized as an inactive prochymase, and dipeptidylpeptidase I (DPPI) is necessary for chymase activation in the secretory granules (5). DPPI is a thiol proteinase with a pH optimum of 6.0 and the pH optimum of DPPI is consistent with its proposed fun...

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Mast cell chymase in pulmonary hypertension

Cited by 51 publications

References 9 publications

Morphometric evaluation of murine pulmonary mast cells in experimental hemorrhagic shock

Morphometric evaluation of murine pulmonary mast cells in experimental hemorrhagic shock

Immune Dysregulation and Endothelial Dysfunction in Pulmonary Arterial Hypertension

Role of Chymase-Dependent Angiotensin II Formation in Monocrotaline-Induced Pulmonary Hypertensive Rats

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