Angiotensin receptor regulates cardiac hypertrophy and transforming growth factor-beta 1 expression.

Everett, Allen D.; Tufro-McReddie, Alda; Fisher, Audrey; Gómez, R. Ariel

doi:10.1161/01.hyp.23.5.587

Cited by 187 publications

(98 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…7,32 Previous studies have provided compelling evidence that Ang II induces fibrosis in the heart and kidneys primarily through the TGF␤ 1 pathway. 3,17,19 Therefore, the marked up-regulation of cardiac and renal CTGF mRNA and protein expression found in dTGR is likely to be mediated through TGF␤ 1 . The close co-localization of CTGF gene expression with Col I and Col III mRNA expressions supports this notion.…”

Section: Discussionmentioning

confidence: 99%

“…Ang II may also regulate collagen degradation by attenuating matrix metalloproteinase activities, and by enhancing the production of TIMP-1. [17][18][19][20] We investigated CTGF in transgenic rats harboring human renin and angiotensinogen genes (dTGR). We then examined whether or not calcineurin-dependent pathways participate in regulating CTGF gene expression.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Angiotensin II Induces Connective Tissue Growth Factor Gene Expression via Calcineurin-Dependent Pathways

Finckenberg

Inkinen

Ahonen

et al. 2003

The American Journal of Pathology

102

View full text Add to dashboard Cite

Connective tissue growth factor (CTGF) is a polypeptide implicated in the extracellular matrix synthesis.Previous studies have provided evidence that angiotensin II (Ang II) promotes collagen synthesis and regulates collagen degradation. We investigated whether or not CTGF mediates the profibrotic effects of Ang II in the heart and kidneys and the role of calcineurin-dependent pathways in CTGF gene regulation. In transgenic rats harboring human renin and angiotensinogen genes, Ang II induced an age-dependent increase in myocardial CTGF expression, which was 3.5-fold greater compared to normotensive Sprague Dawley (SD) rats. CTGF overexpression correlated closely with the Ang II-induced rise in blood pressure. CTGF mRNA and protein were located predominantly in areas with leukocyte infiltration, myocardial, and vascular lesions and co-localized with TGF␤ 1 , collagen I, and collagen III mRNA expressions. Ang II induced CTGF mRNA and protein to a lesser extent in the kidneys, predominantly in glomeruli, arterioles, and in the interstitium with ample inflammation. However, no expression was found in the right ventricle or pulmonary arteries. Blockade of calcineurin activity by cyclosporine A completely normalized Ang II-induced CTGF overexpression in heart and kidney, suppressed the inflammatory response, and mitigated Ang II-induced cell proliferation and apoptosis. In contrast, blockade of mTOR (target of rapamycin) pathway by everolimus, further increased the expression of CTGF even though everolimus ameliorated cell proliferation and T-cellmediated inflammation. Our findings provide evidence that CTGF mediates Ang II-induced fibrosis in the heart and kidneys via blood pressure and cal-

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Angiotensin II Induces Connective Tissue Growth Factor Gene Expression via Calcineurin-Dependent Pathways

Finckenberg

Inkinen

Ahonen

et al. 2003

The American Journal of Pathology

102

View full text Add to dashboard Cite

show abstract

“…It has been shown that selective stimulation of 34,35 There is evidence that these actions are under inhibitory control by angiotensin AT 2 receptors. 36 Indeed, angiotensin AT 2 receptor antagonizes both pressor and growth effects of the angiotensin AT 1 receptor 37,38 and the central mediated angiotensin-induced release of vasopressin and drinking.…”

Section: Discussionmentioning

confidence: 99%

Role of bradykinins and nitric oxide in the AT2 receptor-mediated hypotension

et al. 2000

View full text Add to dashboard Cite

Footshocks increases mean arterial pressure and heart rate. Systemic or intracerebroventricular (IVT) administration of losartan, a specific angiotensin AT 1 receptor antagonist, not only inhibited the pressor response to footshocks but resulted in vasodepression. Peripheral or IVT administration of PD 123319, a specific angiotensin AT 2 receptor antagonist, did not alter the haemodynamic response to footshocks. However, simultaneous blockade of angiotensin AT 1 and AT 2 receptors by combined systemic or central administration of losartan and PD 12319, eliminated the vasodepressor response to footshocks unmasked in losartan pretreated rats. Our data suggest that activation of peripheral or brain angiotensin AT 2 receptor mediated the vasodepressor response to footshocks in the presence

show abstract

“…68 -70 Activation of the renin-angiotensin system is an important inducer of tissue hypertrophy and interstitial fibrosis, with angiotensin II acting as a potent growth factor in the myocardium. 68,[71][72][73][74] Although development of LVH is an adaptive response that reduces LV wall stress in the face of elevated arterial pressure, it is also an ominous prognostic sign that predicts a high rate of cardiovascular events. The difference between physiological LVH secondary to physical training and pathological LVH from hypertension is the difference between intermittent load and continuous overload on the heart.…”

Section: Pathophysiologymentioning

confidence: 99%