Involvement of Mast Cells in the Development of Fibrosis in Rats with Postmyocarditis Dilated Cardiomyopathy

Selvaraj, Suresh Palaniyandi; Watanabe, Kenichi; Ma, Minghong; Tachikawa, Hitoshi; Kodama, Makoto; Aizawa, Yoshifusa

doi:10.1248/bpb.28.2128

Cited by 37 publications

(29 citation statements)

References 23 publications

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“…MCs appear to be critical also in remodeling associated with aortocaval fistula-induced HF in rats [29]. Finally, as we stated earlier, MCs have been implicated in postmyocarditis HF, as was found in our earlier studies in rats [7, 30] and by others in mice [31]. Therefore, together with this study in HF of Dahl salt-sensitive rats, it appears that MCs are important component in the pathogenesis of HF irrespective of the etiology.…”

Section: Discussionsupporting

confidence: 52%

Mast cells and ɛPKC: A role in cardiac remodeling in hypertension-induced heart failure

Palaniyandi

Inagaki²,

Mochly‐Rosen

2008

Journal of Molecular and Cellular Cardiology

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Heart failure (HF) is a chronic syndrome in which pathological cardiac remodeling is an integral part of the disease and mast cell (MC) degranulation-derived mediators have been suggested to play a role in its progression. Protein kinase C (PKC) signaling is a key event in the signal transduction pathway of MC degranulation. We recently found that inhibition of εPKC slows down the progression of hypertension-induced HF in salt-sensitive Dahl rats fed a high-salt diet. We therefore determined whether εPKC inhibition affects MC degranulation in this model. Six week-old male Dahl rats were fed with a high-salt diet to induce systemic hypertension, which resulted in concentric left ventricular hypertrophy at the age of 11 weeks, followed by myocardial dilatation and HF at the age of 17 weeks. We administered εV1-2 an εPKC-selective inhibitor peptide (3 mg/Kg/day), δV1-1, a δPKC-selective inhibitor peptide (3 mg/Kg/day), TAT (negative control; at equimolar concentration; 1.6 mg/Kg/day) or olmesartan (angiotensin receptor blocker [ARB] as a positive control; 3mg/Kg/day) between 11 weeks and 17 weeks. Treatment with εV1-2 attenuated cardiac MC degranulation without affecting MC density, myocardial fibrosis, microvessel patency, vascular thickening and cardiac inflammation in comparison to TAT- or δV1-1-treatment. Treatment with ARB also attenuated MC degranulation and cardiac remodeling, but to a lesser extent when compared to εV1-2. Finally, εV1-2 treatment inhibited MC degranulation in isolated peritoneal MCs. Together, our data suggest that εPKC inhibition attenuates pathological remodeling in hypertension-induced HF, at least in part, by preventing cardiac MC degranulation.

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Section: Discussionsupporting

confidence: 52%

Mast cells and ɛPKC: A role in cardiac remodeling in hypertension-induced heart failure

Palaniyandi

Inagaki²,

Mochly‐Rosen

2008

Journal of Molecular and Cellular Cardiology

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“…It has been reported that close association between histamine and CS-E proteoglycan release was demonstrated in human colonic mucosa [39]. We have reported that mast cell stabilization with disodium cromoglycate and IL-10 gene therapy attenuated the myocardial remodeling after EAM [40,41]. A significant reduction in MCD was seen in the CHST15 siRNA treated rats compared to vehicle-treated rats (Fig.…”

Section: Discussionmentioning

confidence: 63%

Small interfering RNA therapy against carbohydrate sulfotransferase 15 inhibits cardiac remodeling in rats with dilated cardiomyopathy

Watanabe

Arumugam

Sreedhar

et al. 2015

Cellular Signalling

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Carbohydrate sulfotransferase 15 (CHST15) is a sulfotransferase responsible for biosynthesis of chondroitin sulfate E (CS-E), which plays important roles in numerous biological events such as biosynthesis of proinflammatory cytokines. However, the effects of CHST15 siRNA in rats with chronic heart failure (CHF) after experimental autoimmune myocarditis (EAM) have not yet been investigated. CHF was elicited in Lewis rats by immunization with cardiac myosin, and after immunization, the rats were divided into two groups and treated with either CHST15 siRNA (2μg/week) or vehicle. Age matched normal rats without immunizations were also included in this study. After 7weeks of treatment, we investigated the effects of CHST15 siRNA on cardiac function, proinflammatory cytokines, and cardiac remodeling in EAM rats. Myocardial functional parameters measured by hemodynamic and echocardiographic studies were significantly improved by CHST15 siRNA treatment in rats with CHF compared with that of vehicle-treated CHF rats. CHST15 siRNA significantly reduced cardiac fibrosis, and hypertrophy and its marker molecules (left ventricular (LV) mRNA expressions of transforming growth factor beta1, collagens I and III, and atrial natriuretic peptide) compared with vehicle-treated CHF rats. CHF-induced increased myocardial mRNA expressions of proinflammatory cytokines [interleukin (IL)-6, IL-1β], monocyte chemoattractant protein-1, and matrix metalloproteinases (MMP-2 and -9), and CHST15 were also suppressed by the treatment with CHST15 siRNA. Western blotting study has confirmed the results obtained from mRNA analysis as CHST15 siRNA treated rats expressed reduced levels of inflammatory and cardiac remodeling marker proteins. Our results demonstrate for the first time, that CHST15 siRNA treatment significantly improved LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM.

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“…Others have shown, however, AMD3100 also prevented the non-canonical activation of sonic hedgehog pathway and the induction of epithelial-mesenchymal transition (EMT) in vitro (53). It is also important to note that both cromolyn and AMD3100 have been shown by others to down-regulate the expression of TGF-β (54, 55). Based on our observation that mast cell-derived IL-13 up-regulation of TGF-β plays a role in the proliferation of stellate cells (Figure 5), it is entirely possible that both cromolyn and AMD3100 may be playing a similar role here.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Mast Cell–Stromal Cell Interactions Promote Growth of Pancreatic Cancer

et al. 2013

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Pancreatic ductal adenocarcinoma (PDAC) exists in a complex desmoplastic microenvironment, which includes cancer-associated fibroblasts (also known as pancreatic stellate cells, PSCs) and immune cells that provide a fibrotic niche that impedes successful cancer therapy. We have found that mast cells are essential for PDAC tumorigenesis. Whether mast cells contribute to the growth of PDAC and/or PSCs is unknown. Here we tested the hypothesis that mast cells contribute to the growth of PSCs and tumor cells, thus contributing to PDAC development. Tumor cells promoted mast cell migration. Both tumor cells and PSCs stimulated mast cell activation. Conversely, mast cell-derived IL-13 and tryptase stimulated PSC proliferation. Treating tumor-bearing mice with agents that block mast cell migration and function depressed PDAC growth. Our findings suggest that mast cells exacerbate the cellular and extracellular dynamics of the tumor microenvironment found in PDAC. Therefore, targeting mast cells may inhibit stromal formation and improve therapy.

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Involvement of Mast Cells in the Development of Fibrosis in Rats with Postmyocarditis Dilated Cardiomyopathy

Cited by 37 publications

References 23 publications

Mast cells and ɛPKC: A role in cardiac remodeling in hypertension-induced heart failure

Mast cells and ɛPKC: A role in cardiac remodeling in hypertension-induced heart failure

Small interfering RNA therapy against carbohydrate sulfotransferase 15 inhibits cardiac remodeling in rats with dilated cardiomyopathy

Dynamic Mast Cell–Stromal Cell Interactions Promote Growth of Pancreatic Cancer

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