scholarly journals Lipid Accumulation and Transforming Growth Factor-β Upregulation in the Kidneys of Rats Administered Angiotensin II

Hypertension ◽  
2005 ◽  
Vol 46 (5) ◽  
pp. 1180-1185 ◽  
Author(s):  
Kan Saito ◽  
Nobukazu Ishizaka ◽  
Masumi Hara ◽  
Gen Matsuzaki ◽  
Masataka Sata ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Growth Factor ◽  
Lipid Accumulation ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

ANGIOTENSIN II TYPE 1 RECEPTOR ANTAGONIST (LOSARTAN) DOWN-REGULATES TRANSFORMING GROWTH FACTOR-β IN EXPERIMENTAL ACUTE PYELONEPHRITIS

2000 ◽  
Vol 164 (1) ◽  
pp. 186-191 ◽  
Author(s):  
ADLI KHALIL ◽  
KJELL TULLUS ◽  
MOIZ BAKHIET ◽  
LARS G. BURMAN ◽  
GEORG JAREMKO ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Growth Factor ◽  
Receptor Antagonist ◽  
Acute Pyelonephritis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

Ovine Fetal Adrenal Synthesis of Cortisol: Regulation by Adrenocorticotropic Angiotensin II and Transforming Growth Factor-β*

Endocrinology ◽  
1991 ◽  
Vol 129 (4) ◽  
pp. 1784-1791 ◽  
Author(s):  
WILLIAM E. RAINEY ◽  
KUNIHIKO OKA ◽  
RONALD R. MAGNESS ◽  
J. IAN MASON
Keyword(s):  
Angiotensin Ii ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Ovine Fetal

scholarly journals TGF-β (Transforming Growth Factor-β) Signaling Protects the Thoracic and Abdominal Aorta From Angiotensin II-Induced Pathology by Distinct Mechanisms

2017 ◽  
Vol 37 (11) ◽  
pp. 2102-2113 ◽  
Author(s):  
Stoyan N. Angelov ◽  
Jie Hong Hu ◽  
Hao Wei ◽  
Nathan Airhart ◽  
Minghui Shi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Abdominal Aorta ◽  
Neutralizing Antibodies ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Specific Loss ◽  
Aortic Pathology ◽  
Thoracic And Abdominal

Objective— The role of TGF-β (transforming growth factor-β) signaling in abdominal aortic aneurysm (AAA) formation is controversial. Others reported that systemic blockade of TGF-β by neutralizing antibodies accelerated AAA development in angiotensin II-infused mice. This result is consistent with other studies suggesting that TGF-β signaling prevents AAA. Development of a therapy for AAA that exploits the protective actions of TGF-β would be facilitated by identification of the mechanisms through which TGF-β prevents AAA. We hypothesized that TGF-β signaling prevents AAA by its actions on aortic medial smooth muscle cells. Approach and Results— We compared the prevalence, severity, and histopathology of angiotensin II-induced AAA among control mice (no TGF-β blockade), mice with antibody-mediated systemic neutralization of TGF-β, and mice with genetically based smooth muscle–specific loss of TGF-β signaling. Surprisingly, we found that systemic—but not smooth muscle–specific—TGF-β blockade significantly increased the prevalence of AAA and tended to increase AAA severity, adventitial thickening, and aortic wall macrophage accumulation. In contrast, abdominal aortas of mice with smooth muscle–specific loss of TGF-β signaling differed from controls only in having a thinner media. We examined thoracic aortas of the same mice. Here we found that smooth muscle–specific loss of Tgfbr2 —but not systemic TGF-β neutralization—significantly accelerated development of aortic pathology, including increased prevalence of intramural hematomas, medial thinning, and adventitial thickening. Conclusion— Our results suggest that TGF-β signaling prevents both abdominal and thoracic aneurysmal disease but does so by distinct mechanisms. Smooth muscle extrinsic signaling protects the abdominal aorta and smooth muscle intrinsic signaling protects the thoracic aorta.

Enalapril decreases cardiac mass and fetal gene expression without affecting the expression of endothelin-1, transforming growth factor β-1, or cardiotrophin-1 in the healthy normotensive rat

2011 ◽  
Vol 89 (3) ◽  
pp. 197-205 ◽  
Author(s):  
Katarina Mackovicova ◽  
Andrea Gazova ◽  
Dana Kucerova ◽  
Beata Gajdacova ◽  
Jan Klimas ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Growth Factors ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Cardiac Hypertrophy ◽  
Left Ventricular Mass ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Left Ventricular ◽  
Ventricular Mass

Angiotensin II can induce cardiac hypertrophy by stimulating the release of growth factors. ACE inhibitors reduce angiotensin II levels and cardiac hypertrophy, but their effects on the healthy heart are largely unexplored. We hypothesized that ACE inhibition decreases left ventricular mass in normotensive animals and that this is associated with altered expression of cardiac fetal genes, growth factors, and endothelial nitric oxide synthase (eNOS). Wistar rats (n = 7 per group) were orally administered with enalapril twice daily for a total daily dose of 5 mg·kg–1·d–1 (ENAP5) or 15 mg·kg–1·d–1 (ENAP15) or vehicle. Systolic blood pressure was measured by the tail-cuff method. Left ventricular expression of cardiac myosin heavy chain-α (MYH6) and -β (MYH7), atrial natriuretic peptide (ANP), endothelin-1 (ET-1), transforming growth factor β-1 (TGFβ-1), cardiotrophin-1 (CT-1), and renal renin were examined by real-time PCR, and eNOS using Western blot. Blood pressure was decreased only in ENAP15 animals (p < 0.05 vs. Control), whereas left ventricular mass decreased after both doses of enalapril (p < 0.05 vs. Control). MYH7 and ANP were reduced in ENAP15, while no changes in ET-1, TGFβ-1, CT-1, and MYH6 mRNA or eNOS protein were observed. Renal renin dose-dependently increased after enalapril treatment. Enalapril significantly decreased left ventricular mass even after 1 week treatment in the normotensive rat. This was associated with a decreased expression of the fetal genes MYH7 and ANP, but not expression of ET-1, CT-1, or TGFβ-1.

scholarly journals Fibulin-2 deficiency attenuates angiotensin II-induced cardiac hypertrophy by reducing transforming growth factor-β signalling

2013 ◽  
Vol 126 (4) ◽  
pp. 275-288 ◽  
Author(s):  
Hangxiang Zhang ◽  
Jing Wu ◽  
Hailong Dong ◽  
Shaukat A. Khan ◽  
Mon-Li Chu ◽  
...  
Keyword(s):  
Body Weight ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Cardiac Hypertrophy ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Mitogen Activated Protein Kinase ◽  
Matrix Metalloproteinase 2 ◽  
Type I

AngII (angiotensin II) is a potent neurohormone responsible for cardiac hypertrophy, in which TGF (transforming growth factor)-β serves as a principal downstream mediator. We recently found that ablation of fibulin-2 in mice attenuated TGF-β signalling, protected mice against progressive ventricular dysfunction, and significantly reduced the mortality after experimental MI (myocardial infarction). In the present study, we investigated the role of fibulin-2 in AngII-induced TGF-β signalling and subsequent cardiac hypertrophy. We performed chronic subcutaneous infusion of AngII in fibulin-2 null (Fbln2−/−), heterozygous (Fbln2+/−) and WT (wild-type) mice by a mini-osmotic pump. After 4 weeks of subpressor dosage of AngII infusion (0.2 μg/kg of body weight per min), WT mice developed significant hypertrophy, whereas the Fbln2−/− showed no response. In WT, AngII treatment significantly up-regulated mRNAs for fibulin-2, ANP (atrial natriuretic peptide), TGF-β1, Col I (collagen type I), Col III (collagen type III), MMP (matrix metalloproteinase)-2 and MMP-9, and increased the phosphorylation of TGF-β-downstream signalling markers, Smad2, TAK1 (TGF-β-activated kinase 1) and p38 MAPK (mitogen-activated protein kinase), which were all unchanged in AngII-treated Fbln2−/− mice. The Fbln2+/− mice consistently displayed AngII-induced effects intermediate between WT and Fbln2−/−. Pressor dosage of AngII (2 mg/kg of body weight per min) induced significant fibrosis in WT but not in Fbln2−/− mice with comparable hypertension and hypertrophy in both groups. Isolated CFs (cardiac fibroblasts) were treated with AngII, in which direct AngII effects and TGF-β-mediated autocrine effects was observed in WT. The latter effects were totally abolished in Fbln2−/− cells, suggesting that fibulin-2 is essential for AngII-induced TGF-β activation. In conclusion our data indicate that fibulin-2 is essential for AngII-induced TGF-β-mediated cardiac hypertrophy via enhanced TGF-β activation and suggest that fibulin-2 is a potential therapeutic target to inhibit AngII-induced cardiac remodelling.

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