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Hypertrophic and inflammatory‐fibrotic cardiac remodeling in a neonatal calf model of pulmonary hypertension
Author(s) -
Brown R. Dale,
Li Min,
Hunter Kendall S.,
Frid Maria G.,
Stenmark Kurt R.
Publication year - 2011
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.25.1_supplement.1031.4
Subject(s) - pulmonary hypertension , medicine , cardiology , fibrosis , inflammation , pathology
We examined pathologic hypertrophy and inflammatory‐fibrotic remodeling of the heart in response to hypoxia‐induced pulmonary hypertension (PH). Neonatal male calves were subjected to 14d hypobaric hypoxia (simulated elevation 4200 m, n=11) or normal atmosphere (n=8). Hemodynamics were determined by catheterization of the right ventricle (RV). Cardiac myocyte size was determined histochemically. mRNA was analyzed by Real‐Time PCR. Chronic hypoxia causes PH measured as increased systolic pulmonary artery pressure (sysPAP) and RV myocyte hypertrophy. Regression analysis of RV gene expression referenced to sysPAP as independent variable demonstrated that expression of hypertrophic (β‐myosin heavy chain; skeletal muscle α‐actin), inflammatory (IL‐1β, monocyte chemotactic peptide‐1), and pro‐fibrotic (ED‐A fibronectin) genes all behave as linear, continuously increasing functions. Increased expression of ED‐A Fn and osteopontin was also detected in LV, although the magnitude was reduced compared to RV. In sum, pathologic hypertrophy and inflammatory‐fibrotic remodeling occur in concert in the RV in direct proportion to the magnitude of developed PH. Activation of pro‐fibrotic genes in LV represents a further adverse outcome of PH. Inflammatory‐fibrotic cardiac remodeling should be considered as a therapeutic target in PH. Supported by The Children's Hospital‐Denver and NIH.