Fibroblast's Phenotypic Changes in Chronic Heart Failure‐induced Pulmonary Fibrosis

Abstract

Chronic heart failure (HF) leads to irreversible changes in the lung architecture including tissue remodeling and the development of pulmonary fibrosis. Data from our rat model show that left‐sided HF induces pulmonary edema, triggering fibroblast remodeling and fibrosis development. We hypothesized that fibroblasts undergo phenotypic changes with chronic exposure to cytokines secreted by neutrophils and/or macrophages in chronic HF. We used our chronic HF rat model and primary cell cultures to determine phenotypic changes related to fibrosis development in pulmonary fibroblasts including increased proliferation and collagen production. Lung fibroblasts isolated from rat lung after 7 days of HF were significantly more proliferative compared to cells isolated from control rat lungs. Collagen production in lung fibroblasts isolated from HF group more than doubled compared to collagen production in control lung fibroblasts. The increased proliferative state of lung fibroblasts in HF group combined with increased collagen production per cell, would translate into a great enhanced fibrogenic phenotype in HF group compared to control group. Lung fibroblasts from HF group also expressed more smooth muscle actin indicating differentiation to a more myofibroblast phenotype. Our data are essential to facilitate the identification of drug targets and treatment strategies to improve outcomes in HF patients.