BIOMAT Database Logo BIOMAT Database Logo

Mineralocorticoid receptor affects AP-1 and nuclear factor-kappab activation in angiotensin II-induced cardiac injury. 2001

A Fiebeler, and F Schmidt, and D N Müller, and J K Park, and R Dechend, and M Bieringer, and E Shagdarsuren, and V Breu, and H Haller, and F C Luft
Franz Volhard Clinic and Max Delbrück Center, Medical Faculty of the Charité, Humboldt University of Berlin, Germany.

Aldosterone is implicated in cardiac hypertrophy and fibrosis. We tested the role of the mineralocorticoid receptor in a model of angiotensin II-induced cardiac injury. We administered spironolactone (SPIRO; 20 mg. kg(-1). d(-1)), valsartan (VAL; 10 mg. kg(-1). d(-1)), or vehicle to rats double transgenic for the human renin and angiotensinogen genes (dTGR). We investigated basic fibroblast growth factor (bFGF), platelet-derived growth factor, transforming growth factor-beta(1), and the transcription factors AP-1 and nuclear factor (NF)-kappaB. We used immunohistochemistry, electrophoretic mobility shift assays, and TaqMan RT-PCR. Untreated dTGR developed hypertension, cardiac hypertrophy, vasculopathy, and fibrosis with a 50% mortality rates at 7 weeks. SPIRO and VAL prevented death and reversed cardiac hypertrophy, while only VAL normalized blood pressure. Both drugs prevented vasculopathy. bFGF was markedly upregulated in dTGR, whereas platelet-derived growth factor-B and transforming growth factor-beta(1) were little changed. VAL and SPIRO suppressed this upregulation. Both AP-1 and NF-kappaB were activated in dTGR compared with controls. VAL and SPIRO reduced both transcription factors and reduced bFGF, collagen I, fibronectin, and laminin in the interstitium. These findings show that aldosterone promotes hypertrophy, cardiac remodeling, and fibrosis, independent of blood pressure. The effects involve AP-1, NF-kappaB, and bFGF. Mineralocorticoid receptor blockade downregulates these effectors and reduces angiotensin II-induced cardiac damage.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010982 Platelet-Derived Growth Factor Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. Platelet Derived Growth Factor,Factor, Platelet-Derived Growth,Growth Factor, Platelet-Derived
D012083 Renin A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19. Angiotensin-Forming Enzyme,Angiotensinogenase,Big Renin,Cryorenin,Inactive Renin,Pre-Prorenin,Preprorenin,Prorenin,Angiotensin Forming Enzyme,Pre Prorenin,Renin, Big,Renin, Inactive
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D002318 Cardiovascular Diseases Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM. Adverse Cardiac Event,Cardiac Events,Major Adverse Cardiac Events,Adverse Cardiac Events,Cardiac Event,Cardiac Event, Adverse,Cardiac Events, Adverse,Cardiovascular Disease,Disease, Cardiovascular,Event, Cardiac
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D000068756 Valsartan A tetrazole derivative and ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKER that is used to treat HYPERTENSION. CGP 48933,Diovan,Kalpress,Miten,N-valeryl-N-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)valine,Nisis,Provas,Tareg,Vals,48933, CGP
D000450 Aldosterone A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Aldosterone, (+-)-Isomer,Aldosterone, (11 beta,17 alpha)-Isomer

Related Publications

A Fiebeler, and F Schmidt, and D N Müller, and J K Park, and R Dechend, and M Bieringer, and E Shagdarsuren, and V Breu, and H Haller, and F C Luft
Angiotensin II, the AT2 receptor, and nuclear factor-kappaB activation.
June 2002, Kidney international,
A Fiebeler, and F Schmidt, and D N Müller, and J K Park, and R Dechend, and M Bieringer, and E Shagdarsuren, and V Breu, and H Haller, and F C Luft
Angiotensin II- and salt-induced kidney injury through Rac1-mediated mineralocorticoid receptor activation.
June 2012, Journal of the American Society of Nephrology : JASN,
A Fiebeler, and F Schmidt, and D N Müller, and J K Park, and R Dechend, and M Bieringer, and E Shagdarsuren, and V Breu, and H Haller, and F C Luft
Globular adiponectin inhibits angiotensin II-induced nuclear factor kappaB activation through AMP-activated protein kinase in cardiac hypertrophy.
January 2010, Journal of cellular physiology,
A Fiebeler, and F Schmidt, and D N Müller, and J K Park, and R Dechend, and M Bieringer, and E Shagdarsuren, and V Breu, and H Haller, and F C Luft
Requirement of nuclear factor-kappaB in angiotensin II- and isoproterenol-induced cardiac hypertrophy in vivo.
May 2005, Circulation,
A Fiebeler, and F Schmidt, and D N Müller, and J K Park, and R Dechend, and M Bieringer, and E Shagdarsuren, and V Breu, and H Haller, and F C Luft
Crucial role of Rho-nuclear factor-kappaB axis in angiotensin II-induced renal injury.
July 2007, American journal of physiology. Renal physiology,
A Fiebeler, and F Schmidt, and D N Müller, and J K Park, and R Dechend, and M Bieringer, and E Shagdarsuren, and V Breu, and H Haller, and F C Luft
[Role of angiotensin II type 1 receptor in activation of nuclear factor-kappaB and activator protein-1 in lung of mice with acute lung injury].
April 2010, Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns,
A Fiebeler, and F Schmidt, and D N Müller, and J K Park, and R Dechend, and M Bieringer, and E Shagdarsuren, and V Breu, and H Haller, and F C Luft
Aldosterone deficiency and mineralocorticoid receptor antagonism prevent angiotensin II-induced cardiac, renal, and vascular injury.
September 2012, Kidney international,
A Fiebeler, and F Schmidt, and D N Müller, and J K Park, and R Dechend, and M Bieringer, and E Shagdarsuren, and V Breu, and H Haller, and F C Luft
Globular adiponectin activates nuclear factor-kappaB and activating protein-1 and enhances angiotensin II-induced proliferation in cardiac fibroblasts.
March 2007, Diabetes,
A Fiebeler, and F Schmidt, and D N Müller, and J K Park, and R Dechend, and M Bieringer, and E Shagdarsuren, and V Breu, and H Haller, and F C Luft
Angiotensin II stimulates endothelial integrin beta3 expression via nuclear factor-kappaB activation.
January 2006, Experimental aging research,
A Fiebeler, and F Schmidt, and D N Müller, and J K Park, and R Dechend, and M Bieringer, and E Shagdarsuren, and V Breu, and H Haller, and F C Luft
Angiotensin II and Aldosterone stimulating NF-kappaB and AP-1 activation in hepatic fibrosis of rat.
January 2007, Regulatory peptides,
Copied contents to your clipboard!