Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cardiac distribution of mast cells was investigated after the induction of acute myocardial infarction in the rat. The left anterior descending coronary artery (LAD) was occluded by ligation in the infarct group, whereas in sham rats only a superficial ligature was placed beside the LAD. Rats of both groups were killed at 4, 7, 14, 21, 35, and 85 days following surgery. Hearts were excised and formalin-fixed. Mast cell densities were monitored in subepicardial and subendocardial layers of the left ventricle (LV) in 6 microns thick toluidine blue-stained cross-sections. In control (non-operated) animals, mast cell densities were comparable in the LV subepicardial and subendocardial layers (1.5-2.0 cells per mm2). Following infarction, the mast cell density at the subepicardial site of the infarction gradually increased, reaching a maximum of 25 cells per mm2 on day 21, while a non-significant increase was observed at the subendocardial site. In the non-infarcted regions, the mast cell density increased transiently to reach a maximum of 7 cells per mm2 on day 35 in the subepicardial layer. Again, changes in mast cell density in the subendocardial layer were non-significant. In the sham group, a gradual increase to 9 cells per mm2 on day 21 and a subsequent decrease to 5 cells per mm2 on day 85 were observed in the subepicardial layers. These findings indicate a massive accumulation of mast cells in the subepicardial layers of the infarcted region and a small but significant effect of the surgical procedure on cardiac mast cell deposition, especially in the outer layers of the left ventricle.
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PMID:Transmural changes in mast cell density in rat heart after infarct induction in vivo. 856 98

In the present study, the possible role of mast cells in ischemia/reperfusion-induced myocardial injury was evaluated in the isolated 'mast cell depleted' rat heart. Hearts isolated from sensitized and non-sensitized rats were perfused according to Langendorff. After 30 min of normoxic perfusion, hearts were challenged with antigen, a procedure which is known to result in a massive mast cell degranulation in sensitized hearts. After another 20 min, both 'mast cell depleted' and control hearts were subjected to 30 min of ischemia followed by 30 min of reperfusion. The release of lactate dehydrogenase (LDH) was determined, to quantitate the extent of irreversible injury of cardiomyocytes. Histamine release was measured to establish mast cell degranulation. Coronary flow (CF) and left ventricular developed pressure (LVDP) were monitored to study the consequences of the procedures on hemodynamic recovery. It was found that both CF and LVDP significantly increased during the first min after antigen challenge. These changes were accompanied by an almost complete degranulation of cardiac mast cells. The increase in CF and LVDP values were rapidly followed by a decrease, reaching minimal values of 159 +/- 4% and 85 +/- 4% of those before administration of antigen, respectively, at 2-3 min after antigen challenge. No effect of antigen challenge on LDH release were found indicating that mast cell degranulation did not compromise myocyte integrity. During reperfusion following 30 min of ischemia both the increase in CF and LVDP in 'mast cell-depleted' hearts were not significantly different from those in control (non-sensitized) hearts. Similarly, at the end of the reperfusion-phase, CF and LVDP values in sensitized hearts were comparable to those in control hearts. Reperfusion results in increased LDH release, which at no point in time was significantly different between sensitized and non-sensitized hearts. In non-sensitized hearts histamine release during the reperfusion phase was not detectable. Therefore, the results indicate that in the isolated rat heart, mast cells are most likely not involved in acute ischemia/reperfusion-induced myocardial injury.
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PMID:Antigen-evoked mast cell degranulation in the isolated rat heart: no effect on subsequent ischemia-reperfusion induced damage. 908 42

We investigated by immunocytochemistry (ICC) the distribution in the rat heart of adrenomedullin (AM), a potent and long-lasting hypotensive peptide which is expressed in the cardiovascular system, where it is known to play a major regulatory role. Hearts were collected from adult male Sprague-Dawley rats, and were perfused for 20 min, according to the Langendorff technique, with endothelin-1 (ET-1) or the mast cell-degranulator compound 48/80. Hearts were frozen, and ICC was performed using standard techniques and a specific anti-rat AM1-50 antibody. We confirmed the presence of a low AM-immunoreactivity in cardiomyocytes and cardiac fibroblasts, as well as in endothelial and smooth muscle cells of coronary vessels. Moreover, we provided evidence of the presence in both atria and ventricles of sparse voluminous AM-positive cells, mainly located near coronary vessels. These cells had the same juxtavascular location of toluidine blue-positive mast cells and their number decreased upon acute exposure to the 48/80 compound. However, ICC showed that in these cells AM was always colocalized with atrial and brain natriuretic peptides. Moreover, AM-storing cells were also positive to MyHC-Apla2, indicating that they share some phenotypic features with immature smooth muscle cells. The number of AM-storing cells underwent a dramatic decrease in response to the potent vasoconstrictor ET-1, suggesting an acute release of stored vasodilatory AM aimed at counteracting coronary constriction. Taken together, our present findings support the hypothesis that these cells may represent a novel subset of endocrine cells, strategically located near blood vessels in the mammalian heart, where they can release vasoactive peptides.
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PMID:Adrenomedullin, ANP and BNP are colocalized in a subset of endocrine cells in the rat heart. 1575 15

Mast cells are found in the heart and contribute to reperfusion injury following myocardial ischemia. Since the activation of A2A adenosine receptors (A2AARs) inhibits reperfusion injury, we hypothesized that ATL146e (a selective A2AAR agonist) might protect hearts in part by reducing cardiac mast cell degranulation. Hearts were isolated from five groups of congenic mice: A2AAR+/+ mice, A2AAR(-/-) mice, mast cell-deficient (Kit(W-sh/W-sh)) mice, and chimeric mice prepared by transplanting bone marrow from A2AAR(-/-) or A2AAR+/+ mice to radiation-ablated A2AAR+/+ mice. Six weeks after bone marrow transplantation, cardiac mast cells were repopulated with >90% donor cells. In isolated, perfused hearts subjected to ischemia-reperfusion injury, ATL146e or CGS-21680 (100 nmol/l) decreased infarct size (IS; percent area at risk) from 38 +/- 2% to 24 +/- 2% and 22 +/- 2% in ATL146e- and CGS-21680-treated hearts, respectively (P < 0.05) and significantly reduced mast cell degranulation, measured as tryptase release into reperfusion buffer. These changes were absent in A2AAR(-/-) hearts and in hearts from chimeric mice with A2AAR(-/-) bone marrow. Vehicle-treated Kit(W-sh/W-sh) mice had lower IS (11 +/- 3%) than WT mice, and ATL146e had no significant protective effect (16 +/- 3%). These data suggest that in ex vivo, buffer-perfused hearts, mast cell degranulation contributes to ischemia-reperfusion injury. In addition, our data suggest that A2AAR activation is cardioprotective in the isolated heart, at least in part by attenuating resident mast cell degranulation.
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PMID:Adenosine A2A receptor activation reduces infarct size in the isolated, perfused mouse heart by inhibiting resident cardiac mast cell degranulation. 1875 81

Cardiac mast cells (MC) are apposed to capillaries within the heart and release renin and proteases capable of metabolizing angiotensins (Ang). Therefore, we hypothesized that mast cell degranulation could alter the rat coronary vascular responsiveness to the arterial delivered Ang I and Ang II, taking into account carboxypeptidase and chymase-1 activities. Hearts from animals that were either pretreated or not with systemic injection of the secretagogue compound 48/80 were isolated and mounted on a Langendorff apparatus to investigate coronary reactivity. The proteolytic activity of the cardiac perfusate from isolated hearts, pretreated or not with the secretagogue, toward Ang I and tetradecapeptide renin substrate was analyzed by HPLC. Coronary vascular reactivity to peptides was not affected by compound 48/80 pretreatment, despite the extensive amount of cardiac MC degranulation. Cardiac MC activation did not modify the generation of both Ang II and Ang 5-10 from Ang I by cardiac perfusate, activities that could be ascribed to MC carboxypeptidase and chymase-1, respectively. An aliskiren-resistant Ang I-forming activity was increased in perfusates from secretagogue-treated hearts. Thus, cardiac MC proteases capable of metabolizing angiotensins do not affect rat coronary reactivity to arterial delivered Ang I and II.
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PMID:Cardiac mast cell proteases do not contribute to the regulation of the rat coronary vascular responsiveness to arterial delivered angiotensin I and II. 2030 88

C57BL/6-Kit(W-sh/W-sh) mice are generally regarded as a mast cell-deficient model, as they lack the necessary kit receptor for mast cell development. Further characterization of this strain, however, indicates that C57BL/6-Kit(W-sh/W-sh) mice also have a disruption in the Corin gene. Corin is a transmembrane serine protease critical for processing atrial natriuretic peptide (ANP) from pro-ANP through proteolytic cleavage. Pro-ANP is produced, stored and released by cardiac myocytes in response to atrial stretch and the stress generated by increased afterload such as increased ventricular pressure from aortic stenosis or myocardial infarction. ANP inhibits the effects of the renin-angiotensin system to preserve homeostasis under conditions of increased hemodynamic load, and changes in the level of its activating enzyme Corin have been observed during the progression to heart failure. Here, we investigate the effect of increased hemodynamic load on Corin-deficient C57BL/6-Kit(W-sh/W-sh) mice. Ten-week old male mice were subjected to transverse aortic constriction for 8 weeks and were monitored for changes in cardiac structure and function by echocardiography. Hearts were collected 8 weeks after surgery for molecular and histological analyses. Corin-deficient C57BL/6-Kit(W-sh/W-sh) mice developed rapidly progressive and substantial left ventricular dilation, hypertrophy, and markedly impaired cardiac function during the 8 weeks after surgery, compared to wildtype mice. Concomitant with this we observed increased levels of ANP transcript, but a lack of prepro-ANP or pro-ANP protein in heart tissue extracted from Corin-deficient mice. Surprisingly, fibrosis was not increased in Corin-deficient mice when compared to wildtype mice. These data indicate that Corin's involvement in ANP processing is a key element in the heart's response to increased hemodynamic load. Further, C57BL/6-Kit(W-sh/W-sh) strain is an effective model for investigating the involvement of Corin and, conversely, a less than optimal model for investigating mast cell, and immunological, functions in certain cardiovascular pathologies.
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PMID:Corin-deficient W-sh mice poorly tolerate increased cardiac afterload. 2190 39

Chronic NG-nitro-l-arginine methyl ester (L-NAME) administration induces cardiac hypertrophy in rodent models. Our aims is to determine the role of c-kit expression in L-NAME induced cardiac hypertrophy. 12-20 week old C57BL/6J mice (5 per group) were administered L-NAME (0.325mg/ml) in the drinking water. Hearts were excised at 1-day, 2-days, 5-days, 2-weeks or 6-weeks; or controls which received no L-NAME. Ventricular cross-sectional wall thickness and individual cardiac myocytes cross-sectional area and cardiomyocyte/nuclear ratio to determine cardiac hypertrophy. Immuno-histochemical staining for c-kit, sca-1 and BCRP undertaken. Six weeks L-NAME administration induced significant cardiac hypertrophy compared to control hearts, evidenced by an increase in the thickness of the cross-sectional free ventricular wall (p<0.05) and an increase in mean individual cross-sectional area of cardiac myocytes in the LV wall (p<0.007). We observed c-kit(+) cells (predominately non-mast cell sub-types) in both healthy mice and in the L-NAME treated mice. C-kit staining in the left ventricular cross sections following L-NAME remained stable at 1 and 2 days compared to controls (p=NS). After 5 days of L-NAME we observed c-kit expression to decrease below control levels (p<0.05) and these lower levels were sustained at 2 and 6 weeks. C-kit expression does not decrease during two days of L-NAME administration, suggesting, firstly, that the later decrease in c-kit is not due to NOS inhibition directly and, secondly, there is the possibility for c-kit(+) cell differentiation into other cell types, possibly inducing myocardial cellular hyperplasia, without significant replacement of the original pool of c-kit(+) cells.
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PMID:Chronic NG-nitro-l-arginine methyl ester (L-NAME) administration in C57BL/6J mice induces a sustained decrease in c-kit positive cells during development of cardiac hypertrophy. 2438 87