Angiotensin II type 1 and 2 receptors and lymphatic vessels modulate lung remodeling and fibrosis in systemic sclerosis and idiopathic pulmonary fibrosis.
OBJECTIVE
To validate the importance of the angiotensin II receptor isotypes and the lymphatic vessels in systemic sclerosis and idiopathic pulmonary fibrosis.


METHODS
We examined angiotensin II type 1 and 2 receptors and lymphatic vessels in the pulmonary tissues obtained from open lung biopsies of 30 patients with systemic sclerosis and 28 patients with idiopathic pulmonary fibrosis. Their histologic patterns included cellular and fibrotic non-specific interstitial pneumonia for systemic sclerosis and usual interstitial pneumonia for idiopathic pulmonary fibrosis. We used immunohistochemistry and histomorphometry to evaluate the number of cells in the alveolar septae and the vessels stained by these markers. Survival curves were also used.


RESULTS
We found a significantly increased percentage of septal and vessel cells immunostained for the angiotensin type 1 and 2 receptors in the systemic sclerosis and idiopathic pulmonary fibrosis patients compared with the controls. A similar percentage of angiotensin 2 receptor positive vessel cells was observed in fibrotic non-specific interstitial pneumonia and usual interstitial pneumonia. A significantly increased percentage of lymphatic vessels was present in the usual interstitial pneumonia group compared with the non-specific interstitial pneumonia and control groups. A Cox regression analysis showed a high risk of death for the patients with usual interstitial pneumonia and a high percentage of vessel cells immunostained for the angiotensin 2 receptor in the lymphatic vessels.


CONCLUSIONS
We concluded that angiotensin II receptor expression in the lung parenchyma can potentially control organ remodeling and fibrosis, which suggests that strategies aimed at preventing high angiotensin 2 receptor expression may be used as potential therapeutic target in patients with pulmonary systemic sclerosis and idiopathic pulmonary fibrosis.
Laboratory of Histomorphometry and Pulmonary Genetics, Department of Pathology, Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP, Brazil, Faculdade de Medicina da Universidade de São Paulo, Department of Pathology, Laboratory of Histomorphometry and Pulmonary Genetics, São Paulo/SP, Brazil.
Edwin Roger
ER
Parra
Laboratory of Histomorphometry and Pulmonary Genetics, Department of Pathology, Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP, Brazil, Faculdade de Medicina da Universidade de São Paulo, Department of Pathology, Laboratory of Histomorphometry and Pulmonary Genetics, São Paulo/SP, Brazil.
Aline Domingos Pinto
AD
Ruppert
Laboratory of Histomorphometry and Pulmonary Genetics, Department of Pathology, Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP, Brazil, Faculdade de Medicina da Universidade de São Paulo, Department of Pathology, Laboratory of Histomorphometry and Pulmonary Genetics, São Paulo/SP, Brazil.
Vera Luiza
VL
Capelozzi
D000368:Aged; D000704:Analysis of Variance; D001706:Biopsy; D005260:Female; D005355:Fibrosis; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000473:pathology*; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology; D042601:Lymphatic Vessels / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis*; D044139:Receptor, Angiotensin, Type 2 / Q000032:analysis*; D012129:Respiratory Function Tests; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000473:pathology*; D018709:Statistics, Nonparametric
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2