Cultured Myofibroblasts Generate Angiotensin Peptidesde Novo

Katwa, Laxmansa C.; Campbell, Scott E.; Tyagi, Suresh C.; Lee, Soon Jin; Cicila, George T.; Weber, Karl T.

doi:10.1006/jmcc.1997.0376

Cited by 109 publications

(65 citation statements)

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“…During the subacute phase of AMI, the population of non-cardiac myocytes increases, affecting LV remodeling through the synthesis of extracellular matrix and the secretion of cytokines/local hormones that interact with cardiomyocytes and non-cardiac myocytes. 25 Buzza et al found that granzyme B was able to cleave proteins involved in extracellular matrix (ie, vitronectin, fibronectin, and laminin), 26 so it is also possible that granzyme B plays an important role in LV remodeling by its matrix-degradation activity.…”

Section: Discussionmentioning

confidence: 99%

Elevation of Plasma Granzyme B Levels After Acute Myocardial Infarction

Kondo

Hojo

Tsuru

et al. 2009

Circ J

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Background: Apoptosis is reported to play an important role in left ventricular (LV) remodeling after acute myocardial infarction (AMI). Granzyme B is a member of the serine esterase family, which has an important role in cellular apoptosis and extracellular matrix degradation. Methods and Results: Peripheral blood samples were obtained from 33 patients with a first-onset AMI treated by percutaneous coronary intervention (mean age: 61.4±8.7 years old) on days 1, 7 and 14 after onset. Plasma levels of tumor necrosis factor (TNF)-α, a soluble form of the Fas ligand (sFasL), and granzyme B were measured. TIMI grade 3 recanalization was accomplished in all patients within 12 h after onset. The LV end-diastolic volume index (LVEDVI) was calculated on day 1 and at 6 months after onset. Plasma levels of TNF-α, sFasL and granzyme B increased significantly on days 7 and 14 after onset of AMI. Stepwise multivariate regression analysis showed that the plasma granzyme B level on day 14 is a significant explanatory variable for changes in the LVEDVI. Conclusions: Plasma levels of granzyme B increased after AMI, which might be an important factor in the progression of late LV remodeling after AMI. (Circ J 2009; 73: 503 -507)

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Section: Discussionmentioning

confidence: 99%

Elevation of Plasma Granzyme B Levels After Acute Myocardial Infarction

Kondo

Hojo

Tsuru

et al. 2009

Circ J

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“…16 Briefly, the heart was resected, and the infarcted area was removed. The tissue was then minced and incubated with collagenase type II (Worthington) in Krebs-Ringer buffer for 30 minutes at 37°C.…”

Section: Protocol 2 (In Vitro Experiment)mentioning

confidence: 99%

“…When the cells were then subjected to Fas-induced apoptosis 16 for 24 hours, the incidence of TUNEL-positive myofibroblasts was significantly lower among cells cultured with sT␤RII-containing serum (16Ϯ2.9%) than among those cultured with normal serum (43Ϯ5.2%; PϽ0.05) (Figure 7). However, such an apoptosis-inhibitory effect by sT␤RII-containing serum was completely canceled by an addition of TGF-␤1 at the concentration of 1 g/mL (Figure 7).…”

Section: Effect Of St␤rii On Fas-induced Apoptosis In Vitro (Protocol 2)mentioning

confidence: 99%

Postinfarction Gene Therapy Against Transforming Growth Factor-β Signal Modulates Infarct Tissue Dynamics and Attenuates Left Ventricular Remodeling and Heart Failure

Okada

Takemura

Kosai³

et al. 2005

Circulation

180

142

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Background— Fibrosis and progressive failure are prominent pathophysiological features of hearts after myocardial infarction (MI). We examined the effects of inhibiting transforming growth factor-β (TGF-β) signaling on post-MI cardiac fibrosis and ventricular remodeling and function. Methods and Results— MI was induced in mice by left coronary artery ligation. An adenovirus harboring soluble TGF-β type II receptor (Ad.CAG-sTβRII), a competitive inhibitor of TGF-β, was then injected into the hindlimb muscles on day 3 after MI (control, Ad.CAG-LacZ). Post-MI survival was significantly improved among sTβRII-treated mice (96% versus control at 71%), which also showed a significant attenuation of ventricular dilatation and improved function 4 weeks after MI. At the same time, histological analysis showed reduced fibrous tissue formation. Although MI size did not differ in the 2 groups, MI thickness was greater and circumference was smaller in the sTβRII-treated group; within the infarcted area, α-smooth muscle actin–positive cells were abundant, which might have contributed to infarct contraction. Apoptosis among myofibroblasts in granulation tissue during the subacute stage (10 days after MI) was less frequent in the sTβRII-treated group, and sTβRII directly inhibited Fas-induced apoptosis in cultured myofibroblasts. Finally, treatment of MI-bearing mice with sTβRII was ineffective if started during the chronic stage (4 weeks after MI). Conclusions— Postinfarction gene therapy aimed at suppressing TGF-β signaling mitigates cardiac remodeling by affecting cardiac fibrosis and infarct tissue dynamics (apoptosis inhibition and infarct contraction). This suggests that such therapy may represent a new approach to the treatment of post-MI heart failure, applicable during the subacute stage.

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“…Previous studies have implicated a role for various fibrogenic factors including endothelin-1 (ET-1) in tissue remodeling/fibrosis following injury (Guarda et al, 1993;Nguyen et al, 1998Nguyen et al, , 2001Rossi et al, 1999;Thai et al, 1999;Bauersachs et al, 2000;Mulder et al, 2000;Fraccarollo et al, 2002;Pfeffer et al, 2000). The myofibroblasts (myoFb) found at the site of myocardial infarction (MI) are known to play a vital role in the accumulation of collagens during repair/remodeling Katwa et al, 1997;Sun et al, 2000;Chintalgattu et al, 2003). Recent studies from our laboratory have shown ET-induced expression of type I collagen in cardiac myoFb (Katwa, 2003).…”

mentioning

confidence: 99%

Role of Protein Kinase Cδ in Endothelin-Induced Type I Collagen Expression in Cardiac Myofibroblasts Isolated from the Site of Myocardial Infarction

Chintalgattu

Katwa²

2004

J Pharmacol Exp Ther

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The role of endothelin-1 (ET) in tissue remodeling/fibrogenesis has been demonstrated in various in vitro and in vivo models. Our previous studies have revealed ET-induced expression of type I collagen in cardiac myofibroblasts (myoFb). Here we report that protein kinase C␦ (PKC␦) and mitogen-activated protein kinase/extracellular signal-regulated kinase-1/2 (MAPK/ERK1/2) play a role in ET-induced type I collagen expression using specific pharmacological inhibitors. The present study also reveals the expression of various isoforms of PKC including PKC␣, PKC␤I, PKC␤II, PKC␥, PKC␦, PKC⑀, PKC, and PKC in cardiac myoFb. Our results from mRNA and protein studies demonstrate that calphostin-C, a PKC inhibitor, decreased the ET-induced type I collagen expression suggesting a role for the PKC pathway. Further treatment with rottlerin, a PKC␦ isoform-specific inhibitor, demonstrated attenuation of 80 to 90% of type I collagen expression induced by ET. However, Go6976 [12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo[2,3-a]pyrrolo [3,4-c]carbazole]], an inhibitor of Ca 2ϩ -dependent PKC isoforms (PKC␣ and PKC␤I), showed little to no effect on ET-stimulated type I collagen expression. Furthermore, the MAPK inhibitor PD98059 (2Ј-amino-3Ј-methoxyflavone) attenuated ETdependent activation of p44/42 MAPK (pERK1/2) and also down-regulated type I collagen expression. Similarly, rottlerin inhibited the activation of p44/42 MAPK (pERK) implicating the involvement of PKC and MAPK/ERK1/2 in ET-induced type I collagen expression. Our protein/DNA array and reverse transcription-polymerase chain reaction results from ET-treated samples showed a significant increase in Sp1 expression. PD98059 and rottlerin decreased ET-induced Sp1 expression, suggesting a possible interaction of Sp1 with PKC␦ and MAPK in ET-induced type I collagen expression in cardiac myoFb.

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Cultured Myofibroblasts Generate Angiotensin Peptidesde Novo

Cited by 109 publications

References 0 publications

Elevation of Plasma Granzyme B Levels After Acute Myocardial Infarction

Elevation of Plasma Granzyme B Levels After Acute Myocardial Infarction

Postinfarction Gene Therapy Against Transforming Growth Factor-β Signal Modulates Infarct Tissue Dynamics and Attenuates Left Ventricular Remodeling and Heart Failure

Role of Protein Kinase Cδ in Endothelin-Induced Type I Collagen Expression in Cardiac Myofibroblasts Isolated from the Site of Myocardial Infarction

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