Angiotensin II–Induced Cardiac Hypertrophy and Hypertension Are Attenuated by Epidermal Growth Factor Receptor Antisense

Kagiyama, Shuntaro; Eguchi, Satoru; Frank, Gerald D.; Inagami, Tadashi; Zhang, Y. Clare; Phillips, M. Ian

doi:10.1161/01.cir.0000030181.63741.56

Cited by 164 publications

(125 citation statements)

References 20 publications

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“…30,33 Ald also mediated its effects via the EGFR. Ald enhanced EGF signaling, resulting in potentiated ERK 1/2 phosphorylation and Ca 2ϩ homeostasis in MDCK cells.…”

Section: Mazak Et Al Angiotensin II and Aldosterone 2797mentioning

confidence: 97%

Aldosterone Potentiates Angiotensin II–Induced Signaling in Vascular Smooth Muscle Cells

et al. 2004

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Background-In a double-transgenic human renin and human angiotensinogen rat model, we found that mineralocorticoid receptor (MR) blockade ameliorated angiotensin II (Ang II)-induced renal and cardiac damage. How Ang II and aldosterone (Ald) might interact is ill defined. Methods and Results-We investigated the effects of Ang II (10 Ϫ7 mol/L) and Ald (10 Ϫ7 mol/L) on extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling in vascular smooth muscle cells (VSMCs) with Western blotting and confocal microscopy. Ang II induced ERK 1/2 and JNK phosphorylation by 2 minutes. Ald achieved the same at 10 minutes. Ang IIϩAld had a potentiating effect by 2 minutes. Two oxygen radical scavengers and the epidermal growth factor receptor (EGFR) antagonist AG1478 reduced Ang II-, Ald-, and combination-induced ERK1/2 phosphorylation. Preincubating the cells with the MR blocker spironolactone (10 Ϫ6 mol/L) abolished Ang II-induced ROS generation, EGFR transactivation, and ERK1/2 phosphorylation. Conclusions-Ald potentiates Ang II-induced ERK-1/2 and JNK phosphorylation. Oxygen radicals, the MR, and the EGFR play a role in early signaling induced by Ang II and Ald in VSMCs. These in vitro data may help explain the effects of MR blockade on Ang II-induced end-organ damage in vivo.

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“…30,33 Ald also mediated its effects via the EGFR. Ald enhanced EGF signaling, resulting in potentiated ERK 1/2 phosphorylation and Ca 2ϩ homeostasis in MDCK cells.…”

Section: Mazak Et Al Angiotensin II and Aldosterone 2797mentioning

confidence: 97%

Aldosterone Potentiates Angiotensin II–Induced Signaling in Vascular Smooth Muscle Cells

et al. 2004

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“…Until now, the popular technology to reduce angiotensin receptors has been the use of antisense oligonucleotides. [13][14][15][16][17][18] RNAi technology not only is highly selective for the subtypes of AT 1a R and AT 1b R but also is more effective than antisense oligonucleotides. For example, a previous study 19 demonstrated a reduction of AT 1 R by 57% to 73% with 1 mol/L concentration of AT 1 R-specific antisense oligonucleotides.…”

Section: Discussionmentioning

confidence: 99%

Selective Silencing of Angiotensin Receptor Subtype 1a (AT _1a R) by RNA Interference

Vázquez

Adjounian²,

Sumners³

et al. 2005

Hypertension

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Abstract-Angiotensin II exerts its physiological effects by activating multiple subtypes of its receptor such as AT 1a -, AT 1b -, and AT 2 -receptors. Because of a high degree of similarity among these G-protein-coupled receptors, it has been difficult to assign diverse physiological actions of angiotensin II through these receptor subtypes. We have developed small interfering RNAs to selectively inhibit the expression of the AT 1a receptor (AT 1a R) subtype. A dsRNA, AT 1 47, was found to be highly selective and efficient in reducing the levels of AT 1a R subtype. Transfection of AT 1a R-expressing CHO cells with dsRNA AT 1 47 resulted in an 80% decrease in the AT 1a R expression. In contrast, dsRNA AT 1 47 showed no significant effects on both AT 1b R and AT 2 R subtypes. A ngiotensin II (Ang II) exerts profound physiological effects on the cardiovascular system by regulating such diverse functions as increases in blood pressure (BP), extracellular fluid volume, hormone secretion, vascular and cardiac remodeling, stimulation of sympathetic nerve activity, and damping of baroreflexes. 1,2 Most, if not all, of these effects are mediated by activation of a single angiotensin receptor subtype (AT 1 R). Since the discovery of 2 subtypes of AT 1 R, AT 1a R, and AT 1b R in rodents, it has been proposed that this diversity of Ang II actions resides in these 2 subtypes. 3 Because AT 1a R and AT 1b R R share 94% sequence similarity, 4 it has been difficult to develop subtype specific antagonists to link AT 1a R and AT 1b R to distinct cardiovascular effects of Ang II. Thus, investigators have relied on the use of genetic targeting of these receptors in mouse models to link them with various phenotypes. 5-8 For example, AT 1a R knockout studies have indicated the role of this receptor in BP regulation, sodium handling, and central dipsogenic responses. 9 However, knockout studies indicate that AT 1b R can partially replace the BP regulatory functions of AT 1a R. 10 These observations indicate that although knockout technology enables us to delineate an overall physiological perspective, it is limited because of the possible expression of compensatory mechanisms during development. Therefore, new and more selective alternatives need to be developed in which the expression of AT 1a R and AT 1b R could be attenuated in adult animals after development.We have taken advantage of recent advances in RNA interference (RNAi) technology to determine whether it can be used to selectively silence the expression of these receptor subtypes. 11 Thus, our objective in this study was to determine whether we could identify a double stranded RNA (dsRNA) sequence that is highly effective and selective for the AT 1a R subtype. Materials and MethodsComplete coding sequence of Rattus rattus AT 1a R (Gen Bank accession number X62295) was used for the selection of target sequences. The sequence was used in the Target Finder and Design Tool provided by Ambion Inc (Austin, Tex). For screening, 3 target sequences spaced throughout the gene were ch...

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“…It is known that EGFR transactivation plays an important role in cardiovascular remodeling (8,20,(30)(31)(32). It has been reported that activation of ADAM12 (8) or ADAM17 (22) could induce the release of HB-EGF and subsequent EGFR phosphorylation, which may eventually lead to cardiomyocyte hypertrophy, while inhibition of ADAM12 or administration of an HB-EGF neutralizing antibody blocked GPCR agonist-stimulated myocyte hypertrophy (8).…”

Section: Fig 5 Atorvastatin Inhibited the Egfr-erk Signaling Pathwamentioning

confidence: 99%

Atorvastatin Slows the Progression of Cardiac Remodeling in Mice with Pressure Overload and Inhibits Epidermal Growth Factor Receptor Activation

et al. 2008

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Angiotensin II–Induced Cardiac Hypertrophy and Hypertension Are Attenuated by Epidermal Growth Factor Receptor Antisense

Abstract: Ang II requires EGFR to mediate ERK activation in VSMCs and the heart. EGFR plays a critical role in the LVH induced by Ang II.

Cited by 164 publications

References 20 publications

Aldosterone Potentiates Angiotensin II–Induced Signaling in Vascular Smooth Muscle Cells

Aldosterone Potentiates Angiotensin II–Induced Signaling in Vascular Smooth Muscle Cells

Selective Silencing of Angiotensin Receptor Subtype 1a (AT _1a R) by RNA Interference

Atorvastatin Slows the Progression of Cardiac Remodeling in Mice with Pressure Overload and Inhibits Epidermal Growth Factor Receptor Activation

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Angiotensin II–Induced Cardiac Hypertrophy and Hypertension Are Attenuated by Epidermal Growth Factor Receptor Antisense

Abstract: Ang II requires EGFR to mediate ERK activation in VSMCs and the heart. EGFR plays a critical role in the LVH induced by Ang II.

Cited by 164 publications

References 20 publications

Aldosterone Potentiates Angiotensin II–Induced Signaling in Vascular Smooth Muscle Cells

Aldosterone Potentiates Angiotensin II–Induced Signaling in Vascular Smooth Muscle Cells

Selective Silencing of Angiotensin Receptor Subtype 1a (AT 1a R) by RNA Interference

Atorvastatin Slows the Progression of Cardiac Remodeling in Mice with Pressure Overload and Inhibits Epidermal Growth Factor Receptor Activation

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Selective Silencing of Angiotensin Receptor Subtype 1a (AT _1a R) by RNA Interference