Current Respiratory Medicine Reviews

Joseph Varon  
The University of Texas Health Science Center
Houston, TX
USA

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Statins Therapy may Change a Course of Lung Fibrosis and Pulmonary Hypertension: A New Indication for Therapy or Just “Statinomania”?

Author(s): Przemyslaw J. Kotyla.

Abstract:

Statins being the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are potent inhibitors of the key enzyme on cholesterol biosynthesis. However, considerable experimental and clinical evidence have shown that statins have pleiotropic effects on respiratory and cardiovascular systems that are beyond their cholesterol-lowering properties. Statins inhibit an early step in the cholesterol biosynthetic pathway. They also inhibit the synthesis of isoprenoids such as farnesylpyrophosphate and geranylgeranylpyrophosphate, which are involved in posttranslational modifications of small signaling molecules such as the Rho GTPases. Inhibition of RhoA geranylgeranylation by statins results in a wide range of cellular functions, such as cell migration, proliferation, and apoptosis. These processes may explain well immunosuppressive and immunomodulatory properties of statins. Recently, rising evidences suggested that RhoA/Rho-kinase pathway was essentially involved in various models of pulmonary hypertension and statins effectively ameliorated pulmonary hypertension. Interaction in Rho/Rac also leads to fibroblast apoptosis and reduction of TGF-dependent fibrogenesis. This indicates the potential of statins in halting progression of lung fibrosis. These properties, however, are not proven enough in a human clinical trial and request further clinical trails, to check whether animal data could be translated directly to humans. This paper reviewed the role and mechanism of action in two pathophysiological states of lungs: pulmonary fibrosis and pulmonary arterial hypertension. And a special emphasis was put on the indication and limitation of statins therapy in these diseases.

Keywords: Lung Fibrosis, Statins Therapy, Pulmonary Hypertension, potent inhibitors, cholesterol biosynthesis, cardiovascular systems

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Article Details

VOLUME: 5
ISSUE: 1
Year: 2009
Page: [21 - 27]
Pages: 7
DOI: 10.2174/157339809787354029