Source:http://linkedlifedata.com/resource/pubmed/id/19581502
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
2009-8-20
|
| pubmed:abstractText |
The molecular mechanism underlying aldosterone/salt-induced cardiovascular injury remains to be defined. This work was undertaken to determine the role of apoptosis signal-regulating kinase 1 (ASK1) in the mechanism underlying aldosterone-induced cardiac injury in vivo. We compared the in vivo effects of 4 weeks of aldosterone/salt treatment on wild-type and ASK1-deficient mice. Aldosterone infusion plus high salt intake in wild-type mice significantly increased blood pressure and urinary albumin excretion and decreased plasma potassium concentrations, and these effects of aldosterone/salt were not affected by ASK1 deficiency. Thus, ASK1 seems to play a minor role in aldosterone-induced hypertension and renal injury. ASK1 deficiency also failed to affect aldosterone-induced cardiac hypertrophy. However, ASK1 deficiency markedly ameliorated aldosterone-induced cardiac injury, eg, the enhancement of cardiac macrophage infiltration, monocyte chemotactic protein 1 expression, interstitial fibrosis, perivascular fibrosis, and transforming growth factor-beta1 and collagen type I expressions. Thus, ASK1 participates in aldosterone-induced cardiac inflammation and fibrosis. Furthermore, the enhancement of NADPH oxidase-mediated cardiac oxidative stress caused by aldosterone infusion was markedly lessened by ASK1 deficiency, which was associated with the significant amelioration by ASK1 deficiency of aldosterone-induced cardiac Nox2 upregulation. Furthermore, aldosterone/salt treatment significantly enhanced cardiac expression of the angiotensin-converting enzyme and angiotensin II type 1 receptor in wild-type mice, whereas the enhancement of these proteins by aldosterone/salt was abolished by ASK1 deficiency. Our results demonstrate that ASK1 is implicated in aldosterone/salt-induced cardiac inflammation and fibrosis through the enhancement of NADPH oxidase-mediated oxidative stress and the upregulation of the cardiac renin-angiotensin system.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aldosterone,
http://linkedlifedata.com/resource/pubmed/chemical/Ccl2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinase 5,
http://linkedlifedata.com/resource/pubmed/chemical/Map3k5 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Peptidyl-Dipeptidase A,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Angiotensin, Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Chloride, Dietary,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
1524-4563
|
| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
54
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
544-51
|
| pubmed:dateRevised |
2011-11-2
|
| pubmed:meshHeading |
pubmed-meshheading:19581502-Albuminuria,
pubmed-meshheading:19581502-Aldosterone,
pubmed-meshheading:19581502-Animals,
pubmed-meshheading:19581502-Blood Pressure,
pubmed-meshheading:19581502-Chemokine CCL2,
pubmed-meshheading:19581502-Female,
pubmed-meshheading:19581502-Fibrosis,
pubmed-meshheading:19581502-Gene Expression,
pubmed-meshheading:19581502-Inflammation,
pubmed-meshheading:19581502-MAP Kinase Kinase Kinase 5,
pubmed-meshheading:19581502-Macrophages,
pubmed-meshheading:19581502-Male,
pubmed-meshheading:19581502-Mice,
pubmed-meshheading:19581502-Mice, Inbred C57BL,
pubmed-meshheading:19581502-Mice, Knockout,
pubmed-meshheading:19581502-Mitogen-Activated Protein Kinases,
pubmed-meshheading:19581502-Myocardium,
pubmed-meshheading:19581502-NADPH Oxidase,
pubmed-meshheading:19581502-Peptidyl-Dipeptidase A,
pubmed-meshheading:19581502-Potassium,
pubmed-meshheading:19581502-Receptor, Angiotensin, Type 1,
pubmed-meshheading:19581502-Sodium,
pubmed-meshheading:19581502-Sodium Chloride, Dietary,
pubmed-meshheading:19581502-Superoxides,
pubmed-meshheading:19581502-Transforming Growth Factor beta1
|
| pubmed:year |
2009
|
| pubmed:articleTitle |
Critical role of apoptosis signal-regulating kinase 1 in aldosterone/salt-induced cardiac inflammation and fibrosis.
|
| pubmed:affiliation |
Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjyo, Kumamoto 860-8556, Japan. kimmitsu@gpo.kumamoto-u.ac.jp.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|