Role of chymase in cigarette smoke-induced pulmonary artery remodeling and pulmonary hypertension in hamsters

Autor: Jin An, Tao Wang, Shang-Fu Zhang, Su-Xia Han, Guang-Ming He, Fuqiang Wen, Ya-Juan Chen, Xiaohong Zhang, Yun-Ye Ning, Lei Chen, Ting Yang, Dan Xu
Rok vydání: 2010
Předmět:
Male
Pulmonary and Respiratory Medicine
medicine.medical_specialty
Serine Proteinase Inhibitors
Time Factors
Hypertension
Pulmonary
Blotting
Western
Smad Proteins
Pulmonary Artery
Gene Expression Regulation
Enzymologic
Muscle hypertrophy
Transforming Growth Factor beta1
Chymases
Cricetinae
Internal medicine
medicine.artery
Ventricular Pressure
medicine
Animals
RNA
Messenger
Risk factor
lcsh:RC705-779
Immunoassay
COPD
Reverse Transcriptase Polymerase Chain Reaction
business.industry
Angiotensin II
Research
Smoking
Chymase
lcsh:Diseases of the respiratory system
Hypertrophy
medicine.disease
Immunohistochemistry
Pulmonary hypertension
Up-Regulation
Enzyme Activation
Disease Models
Animal
Endocrinology
Pulmonary artery
Ventricular Function
Right
Cardiology
business
Oligopeptides
Signal Transduction
Transforming growth factor
Zdroj: Respiratory Research
Respiratory Research, Vol 11, Iss 1, p 36 (2010)
ISSN: 1465-993X
DOI: 10.1186/1465-9921-11-36
Popis: Background Cigarette smoking is an important risk factor for pulmonary arterial hypertension (PAH) in chronic obstructive pulmonary disease (COPD). Chymase has been shown to function in the enzymatic production of angiotensin II (AngII) and the activation of transforming growth factor (TGF)-β1 in the cardiovascular system. The aim of this study was to determine the potential role of chymase in cigarette smoke-induced pulmonary artery remodeling and PAH. Methods Hamsters were exposed to cigarette smoke; after 4 months, lung morphology and tissue biochemical changes were examined using immunohistochemistry, Western blotting, radioimmunoassay and reverse-transcription polymerase chain reaction. Results Our results show that chronic cigarette smoke exposure significantly induced elevation of right ventricular systolic pressures (RVSP) and medial hypertrophy of pulmonary arterioles in hamsters, concurrent with an increase of chymase activity and synthesis in the lung. Elevated Ang II levels and enhanced TGF-β1/Smad signaling activation were also observed in smoke-exposed lungs. Chymase inhibition with chymostatin reduced the cigarette smoke-induced increase in chymase activity and Ang II concentration in the lung, and attenuated the RVSP elevation and the remodeling of pulmonary arterioles. Chymostatin did not affect angiotensin converting enzyme (ACE) activity in hamster lungs. Conclusions These results suggest that chronic cigarette smoke exposure can increase chymase activity and expression in hamster lungs. The capability of activated chymase to induce Ang II formation and TGF-β1 signaling may be part of the mechanism for smoking-induced pulmonary vascular remodeling. Thus, our study implies that blockade of chymase might provide benefits to PAH smokers.
Databáze: OpenAIRE
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