Premium
Interaction between Chronic Intermittent Hypoxia and Aging in the Lung Tissue
Author(s) -
Brinkman Jacqueline,
Torres Marta,
Broytman Oleg,
Farre Ramon,
Almendros Isaac,
Teodorescu Mihaela
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb838
Subject(s) - intermittent hypoxia , lung , copd , hypoxia (environmental) , fibrosis , medicine , matrix metalloproteinase , western blot , elastase , pathology , obstructive sleep apnea , endocrinology , chemistry , biochemistry , gene , enzyme , organic chemistry , oxygen
Rationale Aging is a powerful risk factor for obstructive sleep apnea (OSA). Chronic intermittent hypoxia (CIH), a key feature of OSA has been shown to lead to heterogeneous lung remodeling in rats, consisting of airways fibrosis and peripheral emphysema‐like formations. In humans, it is also known that with aging lung function declines, in part due to senile emphysema. Emphysema is caused by enhanced synthesis of matrix metalloproteinases (MMPs) by alternatively activated (M2‐polarized) macrophages and aberrant expression of neutrophil elastase (NE), a protease that destroys host tissue. The objective of this study is to examine the molecular interactions of aging and CIH in a mouse model. Methods Wild type C57BL/6j, female mice (n=3–4/group), aged 4 months (young) and 23 months (old) were exposed to either CIH, defined as 60 events per hour (40 seconds 20% O 2 and 20 seconds 5% O 2 ), for 6 hours per day, or normoxia (Nx), for 8 weeks. Mouse lungs were excised, frozen at −80 C, and analyzed for macrophage scavenger receptor (MSR1), a macrophage marker and NE by western blot. Total protein was resolved by SDS‐PAGE. Images were quantified by densitometry using ImageJ software. Results Protein levels of MSR1 (Figure 1A): 1) in the 4/CIH group was significantly higher than in the 4/Nx and comparable to 23/Nx group. NE protein levels (Figure 1B): 1) were highest in the 23/CIH and significantly different from 23/Nx group (p<0.05); 2) appeared to be comparable between 4/CIH and 23/Nx groups. Conclusions Lungs exposed to CIH have increased MSR1 protein expression to levels comparable to that of aged lungs; aging amplified the effects of CIH on NE levels. These results suggest that CIH leads to accelerated aging in the lung; various pathways may be more or less expressed. Support or Funding Information Department of Medicine Pilot Funds