Identification of functional angiotensin II receptors on rat cardiac fibroblasts.

Villarreal, Francisco; Kim, N N; Ungab, GilAnthony; Printz, Morton P.; Dillmann, Wolfgang H.

doi:10.1161/01.cir.88.6.2849

Cited by 317 publications

(192 citation statements)

References 62 publications

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“…The purity of these cultures was 495% cardiac fibroblasts as confirmed by vimentin-positive, desmin-negative and a-smooth muscle actinnegative stainings as previously described. 36 WST-8 assay was performed at 24, 48 and 72 h after infection with Ads or addition of recombinant human HB-EGF (R&D Systems Inc., Minneapolis, MN, USA).…”

Section: Recombinant Adenoviral Vectorsmentioning

confidence: 99%

Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating noncardiomyocytes

Ushikoshi

Takahashi

Chen

et al. 2005

Laboratory Investigation

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Insulin-like growth factor (IGF), hepatocyte growth factor (HGF), and heparin-binding epidermal growth factorlike growth factor (HB-EGF) are cardiogenic and cardiohypertrophic growth factors. Although the therapeutic effects of IGF and HGF have been well demonstrated in injured hearts, it is uncertain whether natural upregulation of HB-EGF after myocardial infarction (MI) plays a beneficial or pathological role in the process of remodeling. To answer this question, we conducted adenoviral HB-EGF gene transduction in in vitro and in vivo injured heart models, allowing us to highlight and explore the HB-EGF-induced phenotypes. Overexpressed HB-EGF had no cytoprotective or additive death-inducible effect on Fas-induced apoptosis or oxidative stress injury in primary cultured mouse cardiomyocytes, although it significantly induced hypertrophy of cardiomyocytes and proliferation of cardiac fibroblasts. Locally overexpressed HB-EGF in the MI border area in rabbit hearts did not improve cardiac function or exhibit an angiogenic effect, and instead exacerbated remodeling at the subacute and chronic stages post-MI. Namely, it elevated the levels of apoptosis, fibrosis, and the accumulation of myofibroblasts and macrophages in the MI area, in addition to inducing left ventricular hypertrophy. Thus, upregulated HB-EGF plays a pathophysiological role in injured hearts in contrast to the therapeutic roles of IGF and HGF. These results imply that regulation of HB-EGF may be a therapeutic target for treating cardiac hypertrophy and fibrosis. Laboratory Investigation (2005) 85, 862-873.

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Section: Recombinant Adenoviral Vectorsmentioning

confidence: 99%

Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating noncardiomyocytes

Ushikoshi

Takahashi

Chen

et al. 2005

Laboratory Investigation

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“…Cultured rat cardiac fibroblasts do not express markers for striated or smooth muscle cells or endothelial cells. [32][33][34][35][36] Adult cardiac myocytes were isolated by perfusion with collagenase. Hearts were excised from heparinized (1000 U IP) and anesthetized (ketamine, 100 mg IP) male Sprague-Dawley rats (350 to 400 g), arrested in cold isotonic saline containing 20 mmol/L KCl, and perfused retrograde via the aorta at a constant pressure of 70 mm Hg by using a pH 7.4 Krebs-Henseleit (KH) solution containing (mmol/L) NaCl 138, KCI 4.7, CaCl2 1.5, MgSO4 1.2, glucose 10, pyruvate 10, HEPES 5, and 20 U/L insulin.…”

Section: Preparation Of Cardiac Myocytes and Fibroblastsmentioning

confidence: 99%

“…29,30 In cell culture, activation of cardiac fibroblast 032-ARs induces fibroblast growth and production of a factor or factors that stimulate growth of cardiac myocytes. 31 Similarly, angiotensin II receptors are present in both cardiac myocytes and cardiac fibroblasts in culture, [32][33][34][35] and in both cell types, the AT, receptor subtype mediates a growth response.32 '33 Thus, the physiological effects of 18-AR agonists and angiotensin II in cardiac muscle might reflect, in part, activation of fibroblasts. However, it is unknown whether the physiological effects of a,-AR agonists might be mediated through a,-ARs in fibroblasts.…”

mentioning

confidence: 99%

Cloning of the rat alpha 1C-adrenergic receptor from cardiac myocytes. alpha 1C, alpha 1B, and alpha 1D mRNAs are present in cardiac myocytes but not in cardiac fibroblasts.

Stewart

Rokosh

Bailey

et al. 1994

Circulation Research

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a,-Adrenergic receptor (AR) activation in cardiac muscle has several different physiological effects that might be mediated through different a,-AR subtypes. Two a,-AR subtypes have been cloned from the rat, the alB and the alD; both are present in adult rat heart. A third subtype, the a,c, cloned from the cow and human, was reported to be absent in the rat. However, we recently found alc mRNA in adult rat heart by using a partial alc cDNA. Thus, all three cloned a,-AR subtypes are present in the heart, but it is unknown whether each is expressed in cardiac myocytes or in cardiac fibroblasts.In the present study, the full-length rat alc-AR was cloned from cultured neonatal cardiac myocytes. alc mRNA transcripts of 3, 9.5, and 11 kb were present in adult rat heart by Northern blot analysis. alB-, alc-, and alD-subtype mRNAs were each present in isolated adult and neonatal cardiac I n cardiac muscle, a1-adrenergic receptor (AR) activation has several different physiological effects, including control of energy production,' increased and decreased inotropy and chronotropy,2-4 preconditioning against ischemic injury,5 reduction of myocardial stunning,6 and induction of cardiac myocyte hypertrophy and gene transcription.7-9 In addition, in the coronary arteries, a,-AR activation produces vasoconstriction.10"11 a,-ARs belong to the superfamily of G proteincoupled receptors with seven transmembrane domains. Like the other receptors for catecholamines -,-AR, a2-AR, and dopaminergic -a,-ARs constitute a multigene family. Three a,-AR subtypes have been cloned: the aiB from the hamster,'2 dog,13 rat,14-16 and human17'18; the aD from the rat'5'19 and human18; and the alc from the cow20 and human.18'2' In earlier studies, the mRNAs for two of these a,-AR subtypes were found in adult rat heart, the a1B1522 and the a1D.'5 Recently, we have shown that alc mRNA is also present in adult rat heart,23 contrary to prior reports.15,20,24 Thus, the mRNAs for all three cloned a,-ARs-the alB, the alD, and the ailc-are expressed in adult rat cardiac muscle.Two a,-AR subtypes had been defined by radioligand binding studies of native receptors in a variety of rat Received May 25, 1994; accepted July 29, 1994 tissues including the heart: the aClA and the a1B (for a review, see Reference 25). The cloned af, corresponds to the native alB-AR.'9'26'27 The cloned aiD, thought originally to correspond to the native alA,A' in fact appears to represent a distinct subtype.18"9'23'27 The cloned aic, thought originally to be an a,-AR not recognized in studies of native receptors,20.24 now appears to be the molecular equivalent of the native classical 1A. 18.23,27,28 Different physiological effects of a,-AR activation in the heart might be due not only to the presence of different a,-AR subtypes but also to a distinct distribution of a,-AR subtypes between cardiac myocytes and fibroblasts. Precedent exists for the presence of catecholamine receptors on cardiac fibroblasts. For example, 132-ARs are predominant on rat cardiac fibroblasts, wher...

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“…Interleukin-I increased proliferation and collagen synthesis in skin fibroblasts, whereas it inhibited these in cardiac fibroblasts [3]. Important molecular factors shown to mediate phenotypic changes in cardiac fibroblasts in response to injury are angiotensin II [4][5][6][7], transforming growth factor β [8,9], norepinephrine [10] and endothelin-1 [11]. Cardiac myocytes also secrete atrial and brain natriuretic peptides (ANP, BNP) which have potent systemic activities such as natriuresis, diuresis and vasodilation.…”

Section: Introductionmentioning

confidence: 99%

Quantitative analysis of the cardiac fibroblast transcriptome—implications for NO/cGMP signaling

et al. 2004

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SummaryCardiac fibroblasts regulate tissue repair and remodeling in the heart. To quantify transcript levels in these cells we performed a comprehensive gene expression study using serial analysis of gene expression (SAGE). Among 110,169 sequenced tags we could identify 30,507 unique transcripts. A comparison of SAGE data from cardiac fibroblasts with data derived from total mouse heart revealed a number of fibroblast-specific genes. Cardiac fibroblasts expressed a specific collection of collagens, matrix proteins and metalloproteinases, growth factors, and components of signalling pathways. The NO/cGMP signalling pathway was represented by the mRNAs for α 1 and β 1 subunits of guanylyl cyclase, cGMP-dependent protein kinase type I (cGK I) and interestingly the G-kinase anchoring protein GKAP42. The expression of cGK I was verified by RT-PCR and Western Blot. To establish a functional role for cGK I in cardiac fibroblasts we studied its effect on cell proliferation. Selective activation of cGK I with a cGMP-analog inhibited the proliferation of serum-stimulated cardiac fibroblasts which express cGK I, but not higher passage fibroblasts which contain no detectable cGK I. Currently, our data suggest that cGK I mediates the inhibitory effects of the NO/cGMP pathway on cardiac fibroblast growth.Furthermore the SAGE library of transcripts expressed in cardiac fibroblasts provides a basis for future investigations into the pathological regulatory mechanisms underlying cardiac fibrosis.

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Identification of functional angiotensin II receptors on rat cardiac fibroblasts.

Cited by 317 publications

References 62 publications

Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating noncardiomyocytes

Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating noncardiomyocytes

Cloning of the rat alpha 1C-adrenergic receptor from cardiac myocytes. alpha 1C, alpha 1B, and alpha 1D mRNAs are present in cardiac myocytes but not in cardiac fibroblasts.

Quantitative analysis of the cardiac fibroblast transcriptome—implications for NO/cGMP signaling

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