Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart.

Urata, Hidenori; Kinoshita, Akio; Misono, Kunio S.; Bumpus, F. M.; Husain, Ahsan

doi:10.1016/s0021-9258(18)45712-2

Cited by 787 publications

(81 citation statements)

References 42 publications

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“…Chymase, a chymotrypsin-like serine protease (CLP), was originally found in mast cells 6 and later found in the human heart and in the vascular tissue. 7,8 By study of the Ang II generation in human heart tissue, Urata et al noticed that chymase is responsible for more than 80% of Ang II produced in the human heart, whereas only 10% to 20% of Ang II is generated through angiotensin-converting enzyme (ACE). 7 Therefore, it has been considered that chymase is a potent non-ACE angiotensin-generating enzyme to convert Ang I to Ang II.…”

Section: Introductionmentioning

confidence: 99%

“…7,8 By study of the Ang II generation in human heart tissue, Urata et al noticed that chymase is responsible for more than 80% of Ang II produced in the human heart, whereas only 10% to 20% of Ang II is generated through angiotensin-converting enzyme (ACE). 7 Therefore, it has been considered that chymase is a potent non-ACE angiotensin-generating enzyme to convert Ang I to Ang II. 7 Chymase also has an ability to convert big endothelin to endothelin-1, another strong vasoconstrictor in the vascular tissue and tracheal smooth muscle cells.…”

Section: Introductionmentioning

confidence: 99%

“…7 Therefore, it has been considered that chymase is a potent non-ACE angiotensin-generating enzyme to convert Ang I to Ang II. 7 Chymase also has an ability to convert big endothelin to endothelin-1, another strong vasoconstrictor in the vascular tissue and tracheal smooth muscle cells. 9 These observations suggest that CLP/chymase may exert a great influence in regulating contractile activity in various tissues and in different cell types, including cardiac and bronchial airway tissues, as well as vascular and nonvascular smooth muscle cells.…”

Section: Introductionmentioning

confidence: 99%

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Endothelial Angiotensin II Generation Induced by Placenta-derived Factors From Preeclampsia

Wang

Lewis

2008

Reprod. Sci.

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Hypersensitivity to angiotensin II contributes to the increased vasoconstriction in preeclampsia. In this study, we determined whether placenta-derived factors could affect endothelial cell angiotensin II generation. Our results showed that more angiotensin II was produced by endothelial cells treated with preeclampsia placental conditioned medium than the cells treated with normal conditioned medium or untreated controls. To determine which pathway, angiotensin-converting enzyme or nonangiotensin-converting enzyme angiotensin-generating enzyme/chymase, might be involved in preeclampsia conditioned medium induced angiotensin II generation, angiotensin-converting enzyme inhibitor captopril and chymotrypsin inhibitors were applied to the cell culture either separately or in combination. We found that chymotrypsin inhibitor, but not captopril, could attenuate the increased angiotensin II generation. To further test specific effects of the protease on endothelial cell angiotensin II generation, endothelial cells were grown in cell culture inserts and chymotrypsin was added to the upper chamber of the cell culture (apical exposure). The medium in the lower chamber (basal direction) was collected and measured for angiotensin II. Our results showed that apical exposure of endothelial cells to the protease resulted in a concentration-dependent increase in basal release of angiotensin II. Angiotensin II receptor-1 expression was also upregulated in cells treated with preeclampsia conditioned medium or chymotrypsin. This data suggest that placenta-derived factors may activate chymase-angiotensin pathway in endothelial cells. Moreover, increased endothelial cell basal release of angiotensin II in response to the protease stimulation further suggests that angiotensin II levels in the circulation may not necessarily reflect angiotensin II generation within the vascular wall.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Endothelial Angiotensin II Generation Induced by Placenta-derived Factors From Preeclampsia

Wang

Lewis

2008

Reprod. Sci.

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“…The significance of placenta-derived CLP-induced endothelial dysfunction has several implications for studies on the pathophysiology of PE. First, placenta-derived CLP induces endothelial inflammatory responses (demonstrated by upregulation of endothelial selectins), 16 supporting the idea that CLP/chymase is an inflammatory protease; Second, placenta-derived CLP was able to mobilize angiotensin II, a powerful systemic vasoconstrictor, generation by endothelial cells, because CLP/ chymase is a potent non-ACE angiotensin II generating enzyme 23,24 ; lastly, our present study shows that CLPderived from preeclamptic placenta disrupts endothelial junction protein integrity leading to increased endothelial permeability. All of these findings show that in PE, ECs are an important target for CLP, and increased CLP activity leads to the pathophysiology of preeclampsia, that is, exaggerated inflammatory response, augmented vasoconstriction, and increased vascular permeability.…”

Section: Discussionmentioning

confidence: 86%

Placenta-derived Chymotrypsin-like Protease (CLP) Disturbs Endothelial Junctional Structure in Preeclampsia

Lewis

Alexander

et al. 2009

Reprod. Sci.

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Placenta-derived chymotrypsin-like protease may contribute to endothelial activation in preeclampsia. In this study, we determined if placenta-derived chymotrypsin-like protease could disturb endothelial junctional integrity to promote endothelial permeability in preeclampsia. Confluent endothelial cells were cocultured with placental trophoblasts or treated with preeclampsia placenta-conditioned medium. Endothelial junction protein vascular endothelial cadherin expression and distribution were examined by fluorescent staining of endothelial cells with or without depletion of chymotrypsin. The association of endothelial cell junction protein complex VE-cadherin/β-catenin/p120 was examined by a combined immuno-precipitation and immuno-blotting assay. Our results showed that endothelial cells cocultured with preeclampsia trophoblasts or exposed to preeclampsia placental conditioned medium exhibited a discontinuous distribution and reduced expression of vascular endothelial cadherin at cell contact regions. Vascular endothelial cadherin and p120 were expressed in control endothelial cells, but reduced or lost in endothelial cells exposed to preeclampsia placental conditioned medium, suggesting that the junctional protein complex of VE-cadherin/β-catenin/p120 was disrupted in endothelial cells exposed to preeclampsia placental conditioned medium. We also observed that removal of trophoblasts from the coculture system and depletion of the protease from the preeclampsia placental conditioned medium could restore the dysregulated endothelial junction protein expression and distribution. Chymotrypsin also induced a dose dependent increase in endothelial monolayer permeability. We conclude that chymotrypsin-like protease released by the placenta is at least one important mediator responsible for disrupting endothelial cell integrity and inducing endothelial permeability in preeclampsia.

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“…In this context, it is beneficial to use functional diagnosis as a basis for diagnosing a mental condition (Urata et al, 1990). We agree with the opinion of experts that the functional diagnosis of compensatory capabilities of the personality can be represented by blocks that contain extra-nosological features: biological block of adaptive potential; psychological block of mental adaptation; social block of mental adaptation; social support block (Broker et al, 1989;Kocjubinskij et al, 2005;Luca et al, 2020;Rebegea et al, 2019;Urata et al, 1990). It will also be appropriate to study the psychophysiological mechanisms of human stress for the psychophysiological support of various activities.…”

Section: Discussionmentioning

confidence: 99%

Stress Resistance in the Situation of Uncertainty as a Factor of Development of Adaptive Ability of Medical Personnel

Halian

Popovych

et al. 2021

BRAIN

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Aim. The aim of the study is to perform psychological and psychophysiological analysis of the features of stress resistance that provide adaptation of medical personnel in the situation of uncertainty. Materials and methods. The study involved: 125 students of III and IV years of study majoring in “Treatment” and “Nursing”; 95 internship doctors 2-3 years of training in various specializations. 36.84% of the total numbers of studied internship doctors were those whose specialization is characterized by an increased level of stress. Methods: correlation analysis, tests with standardized questionnaires. Result. It was found that the manifestation of open, direct aggression by respondents is an acceptable strategy of interaction, which does not significantly affect adaptability. It has been studied that hostility, as an internal directive of the personality, is often not observed externally and determines the decrease in emotional comfort and violation of adaptation. Conclusions. It is proved that adaptive activity as a system-forming factor is accompanied by a number of psychological, biological and social processes and collectively forms the stress resistance of the personality. It is indicated that the immune system is an important part of the functional systems that form the biological factor of functional diagnosis at the stage of low stress resistance and borderline disorders. It is noted that it is appropriate to use functional diagnosis as a basis for diagnosing a person’s mental state in the development of stress resistance.

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Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart.

Cited by 787 publications

References 42 publications

Endothelial Angiotensin II Generation Induced by Placenta-derived Factors From Preeclampsia

Endothelial Angiotensin II Generation Induced by Placenta-derived Factors From Preeclampsia

Placenta-derived Chymotrypsin-like Protease (CLP) Disturbs Endothelial Junctional Structure in Preeclampsia

Stress Resistance in the Situation of Uncertainty as a Factor of Development of Adaptive Ability of Medical Personnel

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