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Cardiac asthma: TGF-β from the failing heart leads to squamous metaplasia in human airway cells and in the murine lung.
MedLine Citation:
PMID:  22505689     Owner:  NLM     Status:  Publisher    
Abstract BACKGROUND:Cardiac asthma describes symptoms of airflow obstruction due to heart failure. Chronic heart failure is associated with decreased forced expiratory volume in one second (FEV1) and FEV1 improves after heart transplantation. Fibrotic remodeling of the heart and airways is mediated in part, through transforming growth factor (TGF)-β. Blood TGF-β1 concentration correlates with ventricular remodeling in cardiac disease and TGF-β decreases after repair. METHODS:We established a co-culture of normal human bronchial epithelial (NHBE) cells differentiated at air-liquid interface with submerged basal cardiomyoblasts. Airway cells were immunostained with cytokeratin, actin, and involucrin. TGF-β synthesis was assayed using enzyme-linked immunosorbent assay (ELISA). Phosphorylation of Smad in NHBE cells was determined by western blotting. Mice given doxorubicin developed cardiac failure and their airways were histologically examined. RESULTS:Co-culture induced involucrin-positive, squamous metaplasia of NHBE cells and this was attenuated by TGF-β antibody. Total TGF-β1 was increased in co-culture conditioned medium (p<0.001). After 14 days exposure to recombinant TGF-β1 there was squamous transformation of NHBE cells. One week after removing cardiomyoblasts from culture, squamous metaplasia resolved into normal ciliated epithelia. Smad was phosphorylated in NHBE cells with cardiomyoblasts or with recombinant TGF-β1 exposure. The airways of mice with heart failure also demonstrated involucrin-positive squamous transformation CONCLUSIONS:TGF-β from cardiomyoblasts or from the failing heart can cause airway squamous metaplasia via Smad signaling and this is blocked by TGF-β and reversed when cardiac cells are removed from culture. This appears to be an important mechanism for airflow obstruction with heart failure; sometimes described as cardiac asthma.
Tsuyoshi Tanabe; Soichiro Kanoh; William B Moskowitz; Bruce K Rubin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-13
Journal Detail:
Title:  Chest     Volume:  -     ISSN:  1931-3543     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0231335     Medline TA:  Chest     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
*Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, U.S.A.
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