Role of tissue angiotensin II in myocardial remodelling induced by mechanical stress

Yamazaki, Tsutomu; Yazaki, Yoshio

doi:10.1038/sj.jhh.1000747

Cited by 31 publications

(18 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In agreement with our previous findings for other Gq-coupled GPCR in epithelial cells (18), this process does not appear to involve cross-talk with Gi-coupled signaling, as has been described for angiotensin II-mediated ERK1/2 activation in cardiac fibroblasts (57). On the other hand, pharmacological inhibition or siRNA-mediated silencing of PKC completely abrogated angiotensin-induced ERK5 activation in cardiomyocytes or cardiac fibroblasts, consistent with the lack of activation of this cascade in cardiomyocytes isolated from PKC-deficient mice.…”

Section: Discussionsupporting

confidence: 80%

Protein Kinase C (PKC)ζ-mediated Gαq Stimulation of ERK5 Protein Pathway in Cardiomyocytes and Cardiac Fibroblasts

García-Hoz

Sánchez-Fernández

García‐Escudero

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: We have recently described that G␣ q acts as an adaptor protein that facilitates PKC-mediated activation of ERK5. Results: Our results show that PKC is essential for Gq-dependent ERK5 activation in cardiomyocytes and cardiac fibroblasts. Conclusion: This novel signaling axis plays a key role in cardiac hypertrophy programs. Significance: The G␣ q /PKC/ERK5 pathway would be active in such pathological settings, providing new therapeutic targets.

show abstract

Section: Discussionsupporting

confidence: 80%

Protein Kinase C (PKC)ζ-mediated Gαq Stimulation of ERK5 Protein Pathway in Cardiomyocytes and Cardiac Fibroblasts

García-Hoz

Sánchez-Fernández

García‐Escudero

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…85 An in vivo study of spontaneously hypertensive rats has investigated the effect of candesartan cilexetil and compared it with that of the vasodilator hydralazine on blood pressure and cardiovascular structure. 86 While the untreated rats became hypertensive, candesartan cilexetil or hydralazine both blunted the increase in blood pressure. Candesartan reduced left ventricular weight, left ventricular wall thickness, transverse myocyte diameter, the relative amount of V3 myosin heavy chain and interstitial fibrosis.…”

Section: Pharmacological Properties Of Candesartan Cilexetilmentioning

confidence: 98%

“…Stretching cardiomyocytes activated second messengers such as protein kinase C, Raf-1 kinase and mitogen-activated protein (MAP) kinase -increasing protein synthesis, enhancing endothelin (ET)-1 release and activating the Na/K ion exchanger. 86 Pre-treatment with candesartan cilexetil diminished the increases in phenylalanine incorporation, MAP kinase activity and fos gene expression induced by the stretching of cardiomyocytes. 86 The inability of ACE inhibitors to reduce the levels of angiotensin II produced by chymase in the heart also affects local tissue remodelling.…”

Section: Pharmacological Properties Of Candesartan Cilexetilmentioning

confidence: 99%

“…86 Pre-treatment with candesartan cilexetil diminished the increases in phenylalanine incorporation, MAP kinase activity and fos gene expression induced by the stretching of cardiomyocytes. 86 The inability of ACE inhibitors to reduce the levels of angiotensin II produced by chymase in the heart also affects local tissue remodelling. Candesartan cilexetil or enalapril were administered to dogs twice daily for 5 weeks.…”

Section: Pharmacological Properties Of Candesartan Cilexetilmentioning

confidence: 99%

See 1 more Smart Citation

Blocking the tissue renin-angiotensin system: the future cornerstone of therapy

Unger

Azizi

Gg³

2000

J Hum Hypertens

View full text Add to dashboard Cite

The development of angiotensin-converting enzyme inhibitors and selective angiotensin type 1 (AT 1 )-receptor antagonists has provided new insights into understanding the mechanism of the renin-angiotensin system (RAS) in the pathophysiology of cardiovascular disease. There is good evidence from meta-analyses that shows that inhibition of the RAS achieves organ protection features that go beyond blood pressure control. Candesartan cilexetil, a new angiotensin II receptor

show abstract

“…14,15 They underscore the importance of the AT 1 R in tissue remodeling and the pathophysiology of hypertension. 16 Figure 2. Effect of LNSV-AT 1 R-AS treatment on indirect and direct blood pressures in adult renin-transgenic rats.…”

Section: Discussionmentioning

confidence: 99%

Blood Pressure–Independent Attenuation of Cardiac Hypertrophy by AT ₁ R-AS Gene Therapy

et al. 2002

View full text Add to dashboard Cite

Abstract-Our studies have established that a single intracardiac administration of the retroviral vector containing angiotensin II type I receptor antisense gene causes prolonged antihypertensive actions in the spontaneously hypertensive rat. These results suggest that antisense gene therapy is a conceptually valid strategy for the control of hypertension at the genetic level. To evaluate whether attenuation of the pathophysiological aspects of hypertension are dependent on the blood pressure lowering actions of antisense gene therapy, we chose the renin transgenic rat as a hypertensive animal model and cardiac hypertrophy as the hypertension-associated pathophysiology. A single intracardiac administration of the retroviral vector containing angiotensin II type I receptor antisense in the neonatal rat resulted in long-term expression of the antisense transgene in various cardiovascular-relevant tissues, including the heart. This expression was associated with a significant attenuation of cardiac hypertrophy despite its failure to normalize high blood pressure. Developmental studies indicated that cardiac hypertrophy was evident as early as 16 days of age in viral vector-treated control transgenic rats, despite these animals exhibiting normal blood pressure. These observations demonstrate that, in the renin-transgenic rat, the onset of cardiac hypertrophy occurs during development and is prevented without normalization of high blood pressure. Collectively, these results provide further proof of the concept and indicate that antisense gene therapy could successfully target the local tissues' renin-angiotensin system to produce beneficial cardiovascular outcomes. Key Words: antisense elements Ⅲ rat, transgenic Ⅲ renin-angiotensin system Ⅲ hypertension, essential Ⅲ genes L eft ventricular hypertrophy (LVH) is a risk factor for cardiovascular-related mortality. Besides high blood pressure (BP), other hemodynamic factors that affect LVH include increased arterial stiffness, blood viscosity, and volume overload. However, increasing evidence has demonstrated a role for nonhemodynamic factors such as the sympathetic nervous system, the local renin-angiotensin system, aldosterone, and genetic factors in the modulation of BP-independent LVH. [1][2][3][4][5][6][7] Recent clinical and experimental studies have demonstrated that pharmacological agents, such as angiotensin converting enzyme (ACE) inhibitors can reduce LVH independently of a reduction in BP. 8,9 This evidence implicates the role of the tissue-based renin-angiotensin system (RAS) in the development of end-organ damage and demonstrates that the pathophysiology may be independent of high BP. However, it has not been established whether the end-organ damage observed in hypertension is a result of high BP or due to an inherently hyperactive RAS.The renin-transgenic rat (TGR mRen2) has been developed as an animal model of hypertension that exhibits fulminant hypertension and displays cardiac and vascular hypertrophy because of an overexertion of renin in various tiss...

show abstract

Role of tissue angiotensin II in myocardial remodelling induced by mechanical stress

Cited by 31 publications

References 29 publications

Protein Kinase C (PKC)ζ-mediated Gαq Stimulation of ERK5 Protein Pathway in Cardiomyocytes and Cardiac Fibroblasts

Protein Kinase C (PKC)ζ-mediated Gαq Stimulation of ERK5 Protein Pathway in Cardiomyocytes and Cardiac Fibroblasts

Blocking the tissue renin-angiotensin system: the future cornerstone of therapy

Blood Pressure–Independent Attenuation of Cardiac Hypertrophy by AT ₁ R-AS Gene Therapy

Contact Info

Product

Resources

About

Role of tissue angiotensin II in myocardial remodelling induced by mechanical stress

Cited by 31 publications

References 29 publications

Protein Kinase C (PKC)ζ-mediated Gαq Stimulation of ERK5 Protein Pathway in Cardiomyocytes and Cardiac Fibroblasts

Protein Kinase C (PKC)ζ-mediated Gαq Stimulation of ERK5 Protein Pathway in Cardiomyocytes and Cardiac Fibroblasts

Blocking the tissue renin-angiotensin system: the future cornerstone of therapy

Blood Pressure–Independent Attenuation of Cardiac Hypertrophy by AT 1 R-AS Gene Therapy

Contact Info

Product

Resources

About

Blood Pressure–Independent Attenuation of Cardiac Hypertrophy by AT ₁ R-AS Gene Therapy