The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.
Regression of chronic hypoxic pulmonary hypertension by simvastatin.
Reda E Girgis; Shehzin Mozammel; Hunter C Champion; Dechun Li; Xinqi Peng; Larissa Shimoda; Rubin M Tuder; Roger A Johns; Paul M Hassoun (Profiled Authors: Larissa Shimoda; Hunter Champion; Xinqi Peng; Paul Hassoun; Rubin Tuder; Roger Johns; Reda Girgis)
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. firstname.lastname@example.org
American journal of physiology. Lung cellular and molecular physiology 2007;292(5):L1105-10.
The 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitor, simvastatin, has been shown to attenuate chronic hypoxic pulmonary hypertension (CHPH). Here, we assess whether simvastatin is capable of inducing regression of established CHPH and explore potential mechanisms of statin effect. Rats (n = 8 in each group) were exposed to chronic hypoxia (10% Fi(O(2))) for 2 or 4 wk. Simvastatin treatment (20 mg.kg(-1).day(-1)) commenced after 2 wk of hypoxia, at which time CHPH was fully established, reduced mean pulmonary artery pressure (19 +/- 0.5 vs. 27 +/- 0.9 mmHg; P < 0.001), the ratio of right ventricular free wall to left ventricular plus septal weight (0.41 +/- 0.03 vs. 0.54 +/- 0.03; P < 0.001), and medial thickening of small pulmonary arteries (13 +/- 0.4 vs. 16 +/- 0.4%; P < 0.01) compared with 4-wk hypoxic controls. Supplementation with mevalonate (50 mg.kg(-1).day(-1)) prevented the attenuation of CHPH induced by simvastatin during 2 wk of hypoxia. Because statins are known to inhibit Rho-kinase (ROCK), we determined expression of ROCK-1 and -2 in whole lung by Western blot and ROCK activity by phosphorylation of the myosin-binding subunit of myosin phosphatase. Expression of both ROCK-1 and -2 were markedly diminished in simvastatin-treated animals during normoxia and hypoxia (2- and 4-wk) exposure (P < 0.01). ROCK activity was increased threefold under hypoxic conditions and normalized with simvastatin treatment (P < 0.001). We conclude that simvastatin attenuates and induces regression of established CHPH through inhibition of HMG-CoA reductase. Inhibition of ROCK expression and activity may be an important mechanism of statin effect.
This section shows information related to the publication - computed using the fingerprint of the publication - including related publications, related experts and related grants with fingerprints representing significant amounts of overlap between their fingerprint and this publication. The red dots indicate whether those experts or terms appear within the publication, thereby showing potential and actual connections.
Reda E Girgis; Dechun Li; Xinhua Zhan; Joe G N Garcia; Rubin M Tuder; Paul M Hassoun; Roger A JohnsAmerican journal of physiology. Heart and circulatory physiology 2003;285(3):H938-45.
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