Effect of atrial natriuretic peptide and cyclic GMP phosphodiesterase inhibition on collagen synthesis by adult cardiac fibroblasts

Redondo, Juliana; Bishop, June E.; Wilkins, Martin R.

doi:10.1038/sj.bjp.0701994

Cited by 66 publications

(38 citation statements)

References 32 publications

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“…Increased interstitial fibrosis can be explained by paracrine mechanisms, since α 1 -ARs are not expressed in cardiac fibroblasts (57). First, ANF induction was markedly less in the ABKO after TAC (Figure 4), and the natriuretic peptides inhibit fibrosis by direct effects on fibroblasts (58)(59)(60)(61)(62). Thus, impaired upregulation of ANF could partly explain increased fibrosis.…”

Section: Figurementioning

confidence: 99%

1-Adrenergic receptors prevent a maladaptive cardiac response to pressure overload

OʼConnell

Swigart²,

Rodrigo

et al. 2006

Journal of Clinical Investigation

131

139

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An α 1 -adrenergic receptor (α 1 -AR) antagonist increased heart failure in the Antihypertensive and LipidLowering Treatment to Prevent Heart Attack Trial (ALLHAT), but it is unknown whether this adverse result was due to α 1 -AR inhibition or a nonspecific drug effect. We studied cardiac pressure overload in mice with double KO of the 2 main α 1 -AR subtypes in the heart, α 1A (Adra1a) and α 1B (Adra1b). At 2 weeks after transverse aortic constriction (TAC), KO mouse survival was only 60% of WT, and surviving KO mice had lower ejection fractions and larger end-diastolic volumes than WT mice. Mechanistically, final heart weight and myocyte cross-sectional area were the same after TAC in KO and WT mice. However, KO hearts after TAC had increased interstitial fibrosis, increased apoptosis, and failed induction of the fetal hypertrophic genes. Before TAC, isolated KO myocytes were more susceptible to apoptosis after oxidative and β-AR stimulation, and β-ARs were desensitized. Thus, α 1 -AR deletion worsens dilated cardiomyopathy after pressure overload, by multiple mechanisms, indicating that α 1 -signaling is required for cardiac adaptation. These results suggest that the adverse cardiac effects of α 1 -antagonists in clinical trials are due to loss of α 1 -signaling in myocytes, emphasizing concern about clinical use of α 1 -antagonists, and point to a revised perspective on sympathetic activation in heart failure.

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Section: Figurementioning

confidence: 99%

1-Adrenergic receptors prevent a maladaptive cardiac response to pressure overload

OʼConnell

Swigart²,

Rodrigo

et al. 2006

Journal of Clinical Investigation

131

139

View full text Add to dashboard Cite

show abstract

“…Early in the 1990s, atrial natriuretic peptide (ANP), an endogenous hormone that is released by the heart in response to myocardial stretch and pressure overload, was found to inhibit collagen synthesis in cardiac fibroblasts via activation of membrane guanylyl cyclase receptors, and increase in intracellular cGMP levels. 13 Recent evidence shows that endogenous ANP and TGF-␤ expression are both upregulated in heart with pressure overload, 14 and ANP plays an important counterregulatory role against TGF-␤-induced cardiac hypertrophy, remodeling, and fibrosis. 8,14,15 In this issue of Circulation Research, Li et al 16 studied the molecular mechanisms of the counterregulatory effects of ANP/cGMP/protein kinase G (PKG) signaling on activated TGF-␤-induced Smad signaling in cardiac cells.…”

Section: A Key Antifibrogenic Mechanism Of Atrial Natriuretic Peptidementioning

confidence: 99%

Cyclic GMP/Protein Kinase G Phosphorylation of Smad3 Blocks Transforming Growth Factor-β–Induced Nuclear Smad Translocation

Buxton

Duan

2008

Circulation Research

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“…In vitro studies demonstrated inhibitory effects on proliferation of vascular smooth muscle cells and CMCs as well as extracellular matrix secretion of cardiac fibroblasts (7)(8)(9). Genetic models revealed insight into the complementary role of these NP with respect to regulation of myocardial structure.…”

mentioning

confidence: 99%

Cardiac hypertrophy in transgenic rats expressing a dominant-negative mutant of the natriuretic peptide receptor B

Langenickel

Buttgereit

Pagel-Langenickel

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

116

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Natriuretic peptides (NP) mediate their effects by activating membrane-bound guanylyl cyclase-coupled receptors A (NPR-A) or B (NPR-B). Whereas the pathophysiological role of NPR-A has been widely studied, only limited knowledge on the cardiovascular function of NPR-B is available. In vitro studies suggest antiproliferative and antihypertrophic actions of the NPR-B ligand C-type NP (CNP). Because of the lack of a specific pharmacological inhibitor, these effects could not clearly be attributed to impaired NPR-B signaling. Recently, gene deletion revealed a predominant role of NPR-B in endochondral ossification and development of female reproductive organs. However, morphological abnormalities and premature death of NPR-B-deficient mice preclude detailed cardiovascular phenotyping. In the present study, a dominant-negative mutant (NPR-B⌬KC) was used to characterize CNP-dependent NPR-B signaling in vitro and in transgenic rats. Here we demonstrate that reduced CNP-but not atrial NP-dependent cGMP response attenuates antihypertrophic potency of CNP in vitro. In transgenic rats, NPR-B⌬KC expression selectively reduced NPR-B but not NPR-A signaling. NPR-B⌬KC transgenic rats display progressive, blood pressure-independent cardiac hypertrophy and elevated heart rate. The hypertrophic phenotype is further enhanced in chronic volume overload-induced congestive heart failure. Thus, this study provides evidence linking NPR-B signaling to the control of cardiac growth.C-type natriuretic peptide ͉ knockdown

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Effect of atrial natriuretic peptide and cyclic GMP phosphodiesterase inhibition on collagen synthesis by adult cardiac fibroblasts

Cited by 66 publications

References 32 publications

1-Adrenergic receptors prevent a maladaptive cardiac response to pressure overload

1-Adrenergic receptors prevent a maladaptive cardiac response to pressure overload

Cyclic GMP/Protein Kinase G Phosphorylation of Smad3 Blocks Transforming Growth Factor-β–Induced Nuclear Smad Translocation

Cardiac hypertrophy in transgenic rats expressing a dominant-negative mutant of the natriuretic peptide receptor B

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