Effects of nonselective endothelin-1 receptor antagonism on cardiac mast cell-mediated ventricular remodeling in rats

2008 ◽  
Vol 294 (3) ◽  
pp. H1251-H1257 ◽  
Author(s):  
David B. Murray ◽  
Jason D. Gardner ◽  
Gregory L. Brower ◽  
Joseph S. Janicki
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Density ◽  
Volume Fraction ◽  
Volume Overload ◽  
Receptor Antagonism ◽  
Collagen Volume Fraction ◽  
Endothelin 1 ◽  
Mast Cell Density ◽  
Chronic Volume Overload

The objective of this study was to investigate the effect a nonselective endothelin-1 (ET-1) receptor antagonist (bosentan) had on the acute myocardial remodeling process including left ventricular (LV) mast cells and matrix metalloproteinase (MMP) activity secondary to volume overload. Additionally, we investigated the overall functional outcome of preventative endothelin receptor antagonism during 14 days of chronic volume overload. LV tissue from sham-operated (Sham), untreated-fistula (Fist), and bosentan (100 mg·kg−1·day−1)-treated animals (Fist + Bos) was analyzed for mast cell density, MMP activity, and myocardial collagen volume fraction at 1 and 5 days after the creation of an aortocaval fistula. When compared with untreated fistulas, bosentan treatment prevented the marked increase in LV mast cell density at 1 day postfistula (3.1 ± 0.3 vs. 1.3 ± 0.3 LV mast cells/mm2, Fist vs. Fist + Bos, P ≤ 0.01). Additionally, the substantial increase in MMP-2 activation in the untreated fistula at 1 day was prevented following bosentan treatment (1.6 ± 0.3 vs. 0.9 ± 0.1 arbitrary activity units, Fist vs. Fist + Bos, P ≤ 0.01). The marked decrease in collagen volume fraction seen in the Fist group (1.4 ± 0.1 vs. 0.8 ± 0.1% myocardial tissue, Sham vs. Fist, P ≤ 0.01) was significantly attenuated following bosentan treatment at both the 1- and 5-day time points. Lastly, a 2-wk preventative treatment with bosentan resulted in significant attenuation of the increase in LV end-systolic and -diastolic volumes compared with those in untreated fistula hearts. In summary, nonselective ET-1 antagonism prevents the acute increases in cardiac mast cell density and MMP activation induced secondary to chronic volume overload. By preventing these events, ET-1 antagonism was efficacious in attenuating ventricular dilatation and limiting the development of structural and functional deficits in the first 2 wk of chronic volume overload. Accordingly, these results are the first to demonstrate that cardiac mast cells are responsive to the endogenous endothelin system in vivo. Another novel finding from this study is that chronic nonspecific endothelin antagonism may inadvertently potentiate ET-1-mediated signaling.

scholarly journals ETAselective receptor antagonism prevents ventricular remodeling in volume-overloaded rats

2009 ◽  
Vol 297 (1) ◽  
pp. H109-H116 ◽  
Author(s):  
David B. Murray ◽  
Ronald McMillan ◽  
Gregory L. Brower ◽  
Joseph S. Janicki
Keyword(s):  
Mast Cell ◽  
Cell Density ◽  
Volume Fraction ◽  
Volume Overload ◽  
Left Ventricular ◽  
Receptor Subtype ◽  
Endothelin Receptor ◽  
Receptor Antagonism ◽  
Myocardial Area ◽  
Mast Cell Density

The objective of this study was to investigate the ability of selective endothelin receptor subtype A (ETA) endothelin receptor antagonism (ETA) to prevent the acute myocardial remodeling process secondary to volume overload. Left ventricular tissue from sham-operated (Sham) and untreated (Fist), and TBC-3214 (Fist + ETA, 25 mg·kg−1·day−1)-treated fistula animals was analyzed for mast cell density, matrix metalloproteinase (MMP) activity, and extracellular collagen volume fraction (CVF) 1 and 5 days following the initiation of volume overload. Compared with Fist, ETA treatment prevented the increase in left ventricular mast cell density at 1 day and 5 days. Additionally, at 1 day postfistula, a substantial decrease in MMP-2 activity below Sham levels was observed following endothelin receptor antagonism (1.7 ± 0.7 vs. 0.3 ± 0.3 vs. 0.9 ± 0.2 arbitrary activity units, Fist vs. Fist + ETA vs. Sham, P ≤ 0.05). This same effect was also seen at 5 days postfistula (1.9 ± 0.3 vs. 0.5 ± 0.1 arbitrary activity units, Fist vs. Fist + ETA, P ≤ 0.05). The marked decrease in myocardial CVF seen in Fist hearts (0.7 ± 0.1 vs. 1.6 ± 0.1% myocardial area, Fist vs. Sham, P ≤ 0.05) was prevented by ETA (1.7 ± 0.1% Fist + ETA, P < 0.05 vs. Fist). This preservation of the collagen matrix was also present on day 5 in the TBC-treated group vs. the Fist group (1.0 ± 0.1 vs. 1.4 ± 0.1%, Fist vs. Fist + ETA, P ≤ 0.01). Furthermore, an 8-wk preventative treatment with ETA significantly attenuated the increase in left ventricular end systolic and diastolic volumes compared with untreated fistula hearts. In conclusion, the novel findings of this study indicate that the activation of cardiac mast cells and subsequent MMP activation/collagen degradation during the acute stages of volume overload are prevented by blockade of the ETAreceptor subtype. Furthermore, by preventing these events, ET-1 antagonism was efficacious in attenuating ventricular dilatation and limiting the development of structural and functional deficits.

scholarly journals Prevention of adverse cardiac remodeling to volume overload in female rats is the result of an estrogen-altered mast cell phenotype

2012 ◽  
Vol 302 (3) ◽  
pp. H811-H817 ◽  
Author(s):  
Hong Lu ◽  
Giselle C. Meléndez ◽  
Scott P. Levick ◽  
Joseph S. Janicki
Keyword(s):  
Mast Cell ◽  
Cell Density ◽  
Cardiac Remodeling ◽  
Sham Group ◽  
Volume Fraction ◽  
Volume Overload ◽  
Female Rats ◽  
Cell Phenotype ◽  
Mast Cell Density ◽  
Tnf Α

Previously, we have reported sex differences in the cardiac remodeling response to ventricular volume overload whereby male and ovariectomized (OVX) female rats develop eccentric hypertrophy, and intact (Int) female rats develop concentric hypertrophy. In males, this adverse remodeling has been attributed to an initial cascade of events involving myocardial mast cell and matrix metalloproteinase activation and extracellular collagen matrix degradation. The objective of this study was to determine the effect of female hormones on this initial cascade. Accordingly, an aortocaval fistula (Fist) was created in 7-wk-old Int and OVX rats, which, together with sham-operated (sham) controls, were studied at 1, 3, and 5 days postsurgery. In Int-Fist rats, myocardial mast cell density, collagen volume fraction, endothelin (ET)-1, stem cell factor (SCF), and TNF-α remained at control levels or were minimally elevated throughout the study period. This was not the case in the OVX-Fist group, where the initial response included significant increases in mast cell density, collagen degradation, ET-1, SCF, and TNF-α. These events in the OVX-Fist group were abolished by prefistula treatment with a mast cell stabilizer nedocromil. Of note was the observation that ET-1, TNF-α, SCF, and collagen volume fraction values for the OVX-sham group were greater than those of the Int-sham group, suggesting that the reduction of female hormones alone results in major myocardial changes. We concluded that female hormone-related cardioprotection to the volume stressed myocardium is the result of an altered mast cell phenotype and/or the prevention of mast cell activation.

Lung mast cell density and distribution in chronically hypoxic animals

1977 ◽  
Vol 42 (2) ◽  
pp. 174-178 ◽  
Author(s):  
A. Tucker ◽  
I. F. McMurtry ◽  
A. F. Alexander ◽  
J. T. Reeves ◽  
R. F. Grover
Keyword(s):  
Cell Proliferation ◽  
Pulmonary Hypertension ◽  
Mast Cell ◽  
Mast Cells ◽  
Cell Density ◽  
Mammalian Species ◽  
Cell Hyperplasia ◽  
Mast Cell Density ◽  
Lung Mast Cell ◽  
Mast Cell Hyperplasia

Changes in the density and distribution of pulmonary mast cells were determined in six mammalian species exposed to hypobaric hypoxia (PB = 435 Torr) for 19–48 days. Control animals were studied at 1,600 m (PB = 635 Torr). Total lung mast cell hyperplasia was observed only in calves exposed to high altitude. Pigs, rats, and sheep exhibited small, but insignificant, increases in mast cell density. Perivascular mast cell proliferation adjacent to vessels of 30–500 mum in diameter was seen in both calves and pigs. Bronchial, alveolar septal, and systemic tissue (tongue) mast cell hyperplasia was not observed in any of the species. Three indices of pulmonary hypertension (right ventricular hypertrophy, medial thickness of pulmonary arteries, and pulmonary arterial pressure) correlated with perivascular mast cell density. The findings indicate that perivascular mast cell proliferation may relate more to the morphological pulmonary vascular changes and to pulmonary hypertension than to hypoxia, leading to the speculation that mast cells increase in number in response to the hypertension, rather than to mediate and maintain the hypertension.

The role of tumour infiltrating mast cells (TIM) in gastric carcinoma remains an enigma : Clinicopathological correlation of mast cell density

2019 ◽  
Vol 5 (4) ◽  
pp. 210-216
Author(s):  
Dr. C.D. Anand ◽  
◽  
Dr. Shivashekar G. ◽  
Dr. Muthu Sudalaimuthu ◽  
Dr. Amitkumar Kalaivani ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Gastric Carcinoma ◽  
Cell Density ◽  
Clinicopathological Correlation ◽  
Mast Cell Density

Response of cardiac mast cells to atrial natriuretic peptide

2007 ◽  
Vol 293 (2) ◽  
pp. H1216-H1222 ◽  
Author(s):  
David B. Murray ◽  
Jason D. Gardner ◽  
Scott P. Levick ◽  
Gregory L. Brower ◽  
Loren G. Morgan ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Ventricular Remodeling ◽  
Volume Overload ◽  
Mast Cell Degranulation ◽  
Aortocaval Fistula ◽  
Chronic Volume Overload ◽  
Atrial Natriuretic

Previously, our laboratory demonstrated that cardiac mast cell degranulation induces adverse ventricular remodeling in response to chronic volume overload. The purpose of this study was to investigate whether atrial natriuretic peptide (ANP), which is known to be elevated in chronic volume overload, causes cardiac mast cell degranulation. Relative to control, ANP induced significant histamine release from peritoneal mast cells, whereas isolated cardiac mast cells were not responsive. Infusion of ANP (225 pg/ml) into blood-perfused isolated rat hearts produced minimal activation of cardiac mast cells, similar to that seen in the control group. ANP also did not increase matrix metalloproteinase-2 activity, reduce collagen volume fraction, or alter diastolic or systolic cardiac function compared with saline-treated controls. In a subsequent study to evaluate the effects of natriuretic peptide receptor antagonism on volume overload-induced ventricular remodeling, anantin was administered to rats with an aortocaval fistula. Comparable increases of myocardial MMP-2 activity in treated and untreated rats with an aortocaval fistula were associated with equivalent decreases in ventricular collagen ( P < 0.05 vs. sham-operated controls). Cardiac functional parameters and left ventricular hypertrophy were unaffected by anantin. We conclude that ANP is not a cardiac mast cell secretagogue and is not responsible for the cardiac mast cell-mediated adverse ventricular remodeling in response to volume overload.

scholarly journals Immunohistochemical Expression of Mast Cells Using c-Kit in Various Grades of Oral Submucous Fibrosis

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Musarrat J. Khatri ◽  
Rajiv S. Desai ◽  
G. S. Mamatha ◽  
Meena Kulkarni ◽  
Jay Khatri
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Cell Density ◽  
Toluidine Blue ◽  
Oral Submucous Fibrosis ◽  
Blue Staining ◽  
Mast Cell Density ◽  
Submucous Fibrosis ◽  
Pharmacologically Active

Oral submucous fibrosis (OSF) is a high risk precancerous condition characterized by changes in the connective tissue fibers of lamina propria and deeper parts of mucosa. Mast cells are local residents of connective tissue and have been identified to participate in fibrotic process. These cells produce pharmacologically active substances necessary for the physiological function of our body in response to various stimuli as and when required and also play a significant role in the pathogenesis of oral diseases. Ten healthy volunteers and 30 clinically diagnosed OSF cases with histopathological confirmation were included in the study. Immunohistochemical (c-kit) as well as acidified toluidine blue staining techniques were used to evaluate density and expression of mast cells. The mast cell density assessed using c-kit and toluidine blue showed significant difference in various stages of OSF. In general the mean number of mast cells obtained using c-kit was found to be more than that obtained using toluidine blue in various stages of OSF. The comparison of mast cell densities using immunohistochemistry (c-kit) and toluidine blue stain confirmed that c-kit is a more reliable technique to assess mast cell density in OSF.

scholarly journals High Mast Cell Density Predicts a Favorable Prognosis in Patients with Pancreatic Neuroendocrine Neoplasms

2021 ◽  
Author(s):  
Shengwei Mo ◽  
Liju Zong ◽  
Xianlong Chen ◽  
Xiaoyan Chang ◽  
Zhaohui Lu ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cell ◽  
Mast Cells ◽  
Cell Density ◽  
Immune Cells ◽  
Clinicopathological Parameters ◽  
Neuroendocrine Neoplasms ◽  
Pancreatic Neuroendocrine Neoplasms ◽  
Entire Cohort ◽  
Mast Cell Density

Introduction: Mast cells are involved in allergic diseases, immune regulation, and tumor microenvironment modulation, with both pro- and anti-tumorigenic functions, and could serve as a prognostic factor in various cancers. However, their potential role in pancreatic neuroendocrine neoplasms (PanNENs) is largely unknown. Here, our aim was to investigate the presence of mast cells in PanNENs and evaluate their association with clinicopathological parameters and other common tumor-infiltrating immune cells. Methods: Tissue microarrays containing PanNEN samples from 187 patients were constructed and stained immunohistochemically for CD117, CD15, CD68, CD3, CD4, and CD8. Immune cells were counted from four high-power fields (HPFs; 400×) at maximal concentrations, and the mean counts were calculated per HPF. The cut-off values were set by X-tile. Results: The median (interquartile range) counts of CD117+ mast cells, CD15+ neutrophils, CD68+ macrophages, CD3+ T cells, and CD4+ T cells were 3.5 (2.0–6.0), 3.0 (1.3–6), 3.8 (2.5–5.8), 13 (8.0–24.0), 2.0 (1.0–4.0)/HPF, respectively. CD8+ T cells were not detected. The cut-off values for these immune cells were 1.5/HPF, 6/HPF, 4.8/HPF, 32.5/HPF, and 2/HPF, respectively. Low mast cell density was correlated with higher grades, non-insulinoma, and advanced stages. Moreover, high mast cell infiltration was associated with elevated CD4+ T cell and CD15+ neutrophil counts. Multivariate analysis revealed that high mast cell density was an independent predictor of prolonged progression-free survival in the entire cohort, in pancreatic neuroendocrine tumors, and in intermediate-grade, non-insulinoma, and advanced stage subgroups. Conclusions: These findings suggest a protective role of mast cells in PanNENs.

scholarly journals Overexpression of HIF-1α and Morphological Alterations in the Tongue of Rats Exposed To Secondhand Smoke

2020 ◽  
Vol 31 (3) ◽  
pp. 281-289
Author(s):  
Eleonora de Paula Amaral ◽  
Rodrigo César Rosa ◽  
Renata Margarida Etchebehere ◽  
Ruchele Dias Nogueira ◽  
José Batista Volpon ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Density ◽  
Tobacco Smoke ◽  
Secondhand Smoke ◽  
Smoke Inhalation ◽  
Lower Percentage ◽  
Control Group ◽  
Albino Rats ◽  
Mast Cell Density

Abstract Smoking is a risk factor for serious health problems and is associated with several changes in the tissues of the oral cavity. The aim of this study was to evaluate the collagen percentage, mast cells density, intensity of immunolabeled cells by anti-HIF-1α in the musculature lingual of rats exposed to secondhand smoke. Twenty-seven female Wistar albino rats were divided into three groups: rats not exposed to tobacco smoke inhalation (Control group) (n=7); rats exposed to smoke inhalation for 30 days (TAB 30) (n=10); and rats exposed to smoke inhalation for 45 days (TAB 45) (n=10). Subsequently, the animals were submitted to euthanasia and removal of the tongue for histological and immunohistochemistry processing and analysis. In the groups TAB 30 and TAB 45 there were a lower percentage of collagen, a higher density of mast cells and a greater intensity of anti-HIF-1α immunolabeled cells compared to Control group. There was also a positive and significant correlation between the percentage of collagen and mast cell density. There was not significative difference between TAB 30 e TAB 45 in any of the parameters evaluated. Therefore, the exposure of rats to secondhand smoke for 45 days causes decrease in perimysial collagen fibers, increase in the number of mast cells and increase in the immunolabeling for HIF-1α in lingual muscle cells. The present study was the first to evaluate the percentage of collagen, mast cell density and immunostaining for HIF-1α in rat tongues exposed to tobacco smoke.

scholarly journals Presence of Increased Mast Cells in Infants and Children with Volume and Variety Limited Intake

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 365
Author(s):  
Amy Issa ◽  
Jensen Edwards ◽  
Meenal Singh ◽  
Craig Friesen ◽  
Sarah Edwards
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Density ◽  
Chart Review ◽  
Pediatric Patients ◽  
Retrospective Chart Review ◽  
Feeding Difficulties ◽  
Mast Cell Density ◽  
Cell Densities ◽  
In Infants And Children

Background: Reports indicate patients with feeding difficulties demonstrate signs of inflammation on biopsies, notably eosinophilia, but it is unknown whether mast cell density contributes to variety or volume limitation symptoms. The aim of our study was to evaluate eosinophil and mast cell density of EGD biopsies in pediatric patients with symptoms of decreased volume or variety of ingested foods. Methods: We conducted a single-center, retrospective chart review of EMRs for all new feeding clinic patients between 0 and 17 years of age. Patients were categorized by symptoms at the initial visit as well as eosinophil and mast cell densities in those with EGD biopsies. Ten patients were identified as controls. Results: We identified 30 patients each with volume and variety limitation. Antral mast cell density was increased in 32.1% of variety-limited patients, 37.5% of volume limited patients, and in no controls; Duodenal mast cell density was increased in 32.1% of variety-limited patients, 40.6% of volume-limited patients, and in no controls. Conclusions: In both variety- and volume-limited patients, antral and duodenal mast cell densities were increased. These associations warrant further investigation of the mechanism between mast cells and development of feeding difficulties, allowing more targeted pediatric therapies.

Sign in / Sign up

Export Citation Format

Share Document