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Naturally Occurring Mechanisms for the Resolution of Pulmonary Vascular and Right Ventricular Remodeling
Author(s) -
Shults Nataliia V.,
Suzuki Yuichiro
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.977.9
Subject(s) - medicine , myofibroblast , fibrosis , ventricle , ventricular remodeling , right ventricular hypertrophy , cardiology , muscle hypertrophy , pulmonary fibrosis , pathology , pulmonary hypertension , heart failure
Pulmonary arterial hypertension (PAH) is a lethal disease and improved therapeutic strategies are needed. Increased pulmonary arterial pressure, due to vasoconstriction and vascular remodeling, causes right ventricle (RV) failure and death. The treatment of Sprague‐Dawley rats with the SU5416 injection and the exposure to chronic hypoxia for 3 weeks followed by maintenance in normoxia promotes progressive and severe PAH with pathologic features that resemble human PAH. At 5–17 weeks after the SU5416 injection, PAH is developed with pulmonary vascular remodeling as well as RV hypertrophy and fibrosis. The present study investigated subsequent events that occur in these PAH animals. At 35 weeks after the SU5416 injection, rats still maintained high RV pressure, but pulmonary vascular remodeling was significantly reduced. Metabolomics analysis revealed that lungs of normal rats and rats from the 35‐week time point had different molecular profiles. Despite the maintenance of high RV pressure, the fibrosis was resolved at 35‐weeks. Masson's trichrome stain and Western blotting monitoring collagen 1 determined 12% fibrosis in the RV at 17‐weeks, and this was decreased to 5% at 35‐weeks. The expression of a‐smooth muscle actin (a marker of myofibroblasts) was elevated at 17‐weeks compared to control, and this was normalized at 35‐weeks. Conclusions These results suggest that biological systems possess natural ways to resolve pulmonary and RV remodeling. The resolution of RV fibrosis appears to involve the reduction of myofibroblast‐dependent collagen synthesis. Understanding these endogenous mechanisms should help improve therapeutic strategies to treat PAH and RV failure. Support or Funding Information NIH