Augmented expression of atrial natriuretic polypeptide gene in ventricle of human failing heart.

Saito, Yoshihiko; Nakao, Kazuwa; Arai, Hiroshi; Nishimura, Kazunobu; Okumura, Ken; Obata, Keisuke; Takemura, Genzou; Fujiwara, Hisayoshi; Sugawara, Akira; Yamada, Hisao

doi:10.1172/jci113872

Cited by 232 publications

(107 citation statements)

References 38 publications

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“…Phosphorylation of TAZ and YAP controls their subcellular localization and transcriptional activity (18,37), suggesting that TAZ and YAP may provide TBX5 with responsiveness to regulatory cues. It will be intriguing to examine how these factors are involved in the marked induction of ANF gene expression in cardiac hypertrophy and failure (41,42).…”

Section: Tbx5 Mutations Associated With Hosmentioning

confidence: 99%

A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt–Oram syndrome

Murakami

Nakagawa

Olson³

et al. 2005

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

238

197

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The T-box transcription factor TBX5 plays essential roles in cardiac and limb development. Various mutations in the TBX5 gene have been identified in patients with Holt-Oram syndrome, which is characterized by congenital defects in the heart and upper extremities. In this study, we identified a WW-domain-containing transcriptional regulator TAZ as a potent TBX5 coactivator. TAZ directly associates with TBX5 and markedly stimulates TBX5-dependent promoters by interacting with the histone acetyltransferases p300 and PCAF. YAP, a TAZ-related protein with conserved functional domains, also stimulates TBX5-dependent transcription, possibly by forming a heterodimer with TAZ. TBX5 lacks a PY motif, which mediates the association of other proteins with TAZ, and interacts with TAZ through multiple domains including its carboxyl-terminal structure. Truncation mutants of TBX5 identified in patients with Holt-Oram syndrome were markedly impaired in their ability to associate with and be stimulated by TAZ. These findings reveal key roles for TAZ and YAP in the control of TBX5-dependent transcription and suggest the involvement of these coactivators in cardiac and limb development.transcriptional coactivator ͉ organ development ͉ hereditary birth defects T he activation of specific programs of gene expression during cell differentiation and organ development depends on combinatorial interactions among DNA-binding transcription factors, transcriptional cofactors, and histone-modifying enzymes (1, 2). Additional specificity and fine-tuning of gene expression is achieved by signal-dependent modulation of the expression and activity of the components of such multiprotein transcriptional complexes.Members of the T-box family of transcription factors regulate a variety of developmental processes in vertebrates and invertebrates, including specification of mesoderm, development of the heart, vasculature, and limbs and tumorigenesis (3-5). The T-box, which encodes a conserved 180-amino acid DNA-binding domain, has been identified in at least 18 mammalian T-box genes. In many cases, haploinsufficiency of T-box genes results in dramatic morphological abnormalities, emphasizing the importance of specific thresholds of transcriptional activity of T-box factors for developmental decisions (4). For example, heterozygous mutations in TBX1 have been implicated in 22q11 deletion (DiGeorge) syndrome, characterized by abnormalities in the aortic arch arteries due to defects in neural crest cell migration (4, 6), and mutations in TBX5 cause Holt-Oram syndrome (HOS), which manifests as a variety of cardiac and upper limb abnormalities (7-11).TBX5 is expressed in the embryonic heart and forelimbs and regulates transcription of downstream genes, such as those encoding atrial natriuretic factor (ANF) and fibroblast growth factor 10 (Fgf10) by binding to TBX-binding DNA elements (TBEs) (12-17). Targeted deletion of the Tbx5 gene in mice results in embryonic lethality with severe cardiac defects (13), and mice with limb-specific Tbx5 deletion show no ...

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Section: Tbx5 Mutations Associated With Hosmentioning

confidence: 99%

A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt–Oram syndrome

Murakami

Nakagawa

Olson³

et al. 2005

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

238

197

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“…The amount of ANP synthesized in the ventricles is only approximately one-hundredth of that synthesized in the atria, and the total ANP content of the ventricles is approximately one-thirtieth of that of the atria. However, in the heart failure state, the synthesis and secretion of ANP in the ventricles markedly increases, reaching about the same level of biosynthesis as that in the atria [14]. The peptide synthesized in the atria is stored in the secretory granules, and secreted in response to stimuli via the regulated pathway.…”

Section: Secretion Mechanism Of the Natriuretic Peptide Systemmentioning

confidence: 99%

The Genetic Contribution of the Natriuretic Peptide System to Cardiovascular Diseases

Nakayama

2005

Endocr J

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Abstract. Three types of natriuretic peptides (NP) have been isolated: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). The NP family elicits a number of vascular, renal and endocrine effects that help to maintain blood pressure and extracellular fluid volume. These effects are mediated by the specific binding of NP to cell surface receptors that have been characterized, purified and cloned from cells of the vasculature, kidney, adrenal gland and brain. There are 3 subtypes of NP receptors: type A natriuretic peptide receptor (NPRA), type B natriuretic peptide receptor (NPRB), and type C natriuretic peptide receptor (NPRC). All 3 subtypes affect cellular second messenger activity. NPRA and NPRB are guanylyl cyclase receptors, and their activation increases cGMP levels. Activation of NPRC results in inhibition of adenylyl cyclase activity. Human NPRA has a high structural homology with human NPRB, and contains a highly-conserved guanylyl cyclase domain. ANP and BNP bind primarily to NPRA, which is found in the vasculature, causing vasodilation and inhibition of vascular smooth muscle cell proliferation. The present paper contains a review of NPs and their receptors and the genetic contribution of the NP system to cardiovascular diseases such as essential hypertension and myocardial infarction.

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“…To examine the development of cardiac hypertrophy and interstitial fibrosis, ANP and BNP mRNA levels, as hypertrophy markers, 29,30 and collagen type 1 and fibronectin mRNA levels, known as major extracellular matrix components, 31,32 were quantified. ANP and BNP mRNA levels in OMI hearts were markedly increased compared with those in nonfailing hearts, and this level was comparable with the levels in DCM hearts ( Figure 7).…”

Section: Expression Of Hypertrophy Marker and Extracellular Matrix Gementioning

confidence: 99%

Angiotensin II Type 2 Receptor Is Upregulated in Human Heart With Interstitial Fibrosis, and Cardiac Fibroblasts Are the Major Cell Type for Its Expression

Tsutsumi

Matsubara

Ohkubo

et al. 1998

Circulation Research

216

159

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Abstract-The expression pattern of angiotensin (Ang) II type 2 receptor (AT 2 -R) in the remodeling process of human left ventricles (LVs) remains poorly defined. We analyzed its expression at protein, mRNA, and cellular levels using autopsy, biopsy, or operation LV samples from patients with failing hearts caused by acute (AMI) or old (OMI) myocardial infarction and idiopathic dilated cardiomyopathy (DCM) and also examined functional biochemical responses of failing hearts to Ang II. In autopsy samples from the nonfailing heart group, the ratio of AT 1 -R and AT 2 -R was 59% and 41%, respectively. The expression of AT 2 -R was markedly increased in DCM hearts at protein (3.5-fold) and mRNA (3.1-fold) levels compared with AMI or OMI. AT 1 -R protein and mRNA levels in AMI hearts showed 1.5-and 2.1-fold increases, respectively, whereas in OMI and DCM hearts, AT 1 -R expression was significantly downregulated. AT 1 -R-mediated response in inositol phosphate production was significantly attenuated in LV homogenate from failing hearts compared with nonfailing hearts. AT 2 -R sites were highly localized in the interstitial region in either nonfailing or failing heart, whereas AT 1 -R was evenly distributed over myocardium at lower densities. Mitogen-activated protein kinase (MAPK) activation by Ang II was significantly decreased in fibroblast compartment from the failing hearts, and pretreatment with AT 2 -R antagonist caused an additional significant increase in Ang II-induced MAPK activity (36%). Cardiac hypertrophy suggested by atrial and brain natriuretic peptide levels was comparably increased in OMI and DCM, whereas accumulation of matrix proteins such as collagen type 1 and fibronectin was much more prominent in DCM than in OMI. These findings demonstrate that (1) AT 2 -R expression is upregulated in failing hearts, and fibroblasts present in the interstitial regions are the major cell type responsible for its expression, (2) AT 2 -R present in the fibroblasts exerts an inhibitory effect on Ang II-induced mitogen signals, and (3) AT 1 -R in atrial and LV tissues was downregulated during chronic heart failure, and AT 1 -R-mediated functional biochemical responsiveness was decreased in the failing hearts. Thus, the expression level of AT 2 -R is likely determined by the extent of interstitial fibrosis associated with heart failure, and the expression and function of AT 1 -R and AT 2 -R are differentially regulated in failing human hearts. (Circ Res. 1998;83:1035-1046.)Key Words: angiotensin II type 2 receptor Ⅲ AT 2 receptor Ⅲ angiotensin II type 1 receptor Ⅲ AT 1 receptor, angiotensin II T he presence of 2 isoforms of angiotensin (Ang) II receptor was originally proposed on the basis of differences in sensitivity of receptor-ligand binding to dithiothreitol. Ang type 2 receptor (AT 2 -R), which is insensitive to dithiothreitol and has a high affinity for PD123319 and CGP42112A, was isolated, and this receptor was shown to have the same seventransmembrane domain of AT 1 -R but only minimal homology (see Review i...

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Augmented expression of atrial natriuretic polypeptide gene in ventricle of human failing heart.

Cited by 232 publications

References 38 publications

A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt–Oram syndrome

A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt–Oram syndrome

The Genetic Contribution of the Natriuretic Peptide System to Cardiovascular Diseases

Angiotensin II Type 2 Receptor Is Upregulated in Human Heart With Interstitial Fibrosis, and Cardiac Fibroblasts Are the Major Cell Type for Its Expression

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