Journal: American Journal of Respiratory and Critical Care Medicine

Article Title: Disconnect between Fibrotic Response and Right Ventricular Dysfunction

doi: 10.1164/rccm.201809-1737OC

Figure Lengend Snippet: The antifibrotic agent pirfenidone ameliorates the progression of right ventricle (RV) fibrosis. (A) Schematic representation of the experimental setup. Hearts were collected from pirfenidone- or chow diet–treated mice 21 days after pulmonary artery banding or sham operation. (B) Representative Sirius red staining. Scale bars, 1 mm. (C) Quantification of RV fibrosis. (D) Representative immunohistochemical staining of the murine hearts against vimentin, PDGFRα (platelet-derived growth factor receptor-α), and galectin-3 (n = 3). Scale bars, 500 μm. (E) Representative immunofluorescence staining of the RV fibrotic regions against vimentin, PDGFRα, αSMA (α-smooth muscle actin), and galectin-3 (n = 2). Arrows depict cells showing colocalization of PDGFRα and vimentin or galectin-3. Scale bars, 20 μm. (F) Echocardiographic assessment of RV free wall thickness. Invasive hemodynamic measurement of (G) RV systolic pressure and (H) RV end diastolic pressure. Echocardiographic assessment of (I) cardiac output, (J) tricuspid annular plane systolic excursion, and (K) early peak of RV relaxation velocity. Two-way ANOVA with Bonferroni post hoc test, *P < 0.05. CO = cardiac output; e′ = RV relaxation velocity; PAB = pulmonary artery banding; RVEDP = RV end diastolic pressure; RVFW = RV free wall thickness; RVSP = RV systolic pressure; TAPSE = tricuspid annular plane systolic excursion.

Article Snippet: Pirfenidone (Toronto Research Chemicals) was mixed with normal chow diet at 2.8 g/kg (ssniff Spezialdiäten) and provided ad libitum to mice.

Techniques: Staining, Immunohistochemical staining, Derivative Assay, Immunofluorescence

Journal: American Journal of Respiratory and Critical Care Medicine

Article Title: Disconnect between Fibrotic Response and Right Ventricular Dysfunction

doi: 10.1164/rccm.201809-1737OC

Figure Lengend Snippet: Disconnect between right ventricular (RV) fibrosis and function. Fibrosis and function were assessed 21 days after the pulmonary artery banding operation in control and treated mice (galectin-3 inhibitor N-acetyllactosamine, galectin-3 knock-out mice, pirfenidone). (A) Correlation of RV fibrosis with RV end diastolic pressure (RVEDP) (catheter derived), and (B) tricuspid annular plane systolic excursion (TAPSE) (echo-derived). Mann-Whitney test and nonparametric correlation (Spearman). Linear regression (full line) with 95% confidence intervals (dashed lines). (C) Pooled data representing RV fibrosis area, RVEDP, tau (time constant of monoexponential curve fitting model of RV diastolic pressure decay), cardiac output, TAPSE, and RV relaxation velocity. CO = cardiac output; e′ = RV relaxation velocity; PAB = pulmonary artery banding.

Article Snippet: Pirfenidone (Toronto Research Chemicals) was mixed with normal chow diet at 2.8 g/kg (ssniff Spezialdiäten) and provided ad libitum to mice.

Techniques: Knock-Out, Derivative Assay, MANN-WHITNEY

Journal: Chembiochem : a European journal of chemical biology

Article Title: Galectin-3-Binding Glycomimetics that Strongly Reduce Bleomycin-Induced Lung Fibrosis and Modulate Intracellular Glycan Recognition.

doi: 10.1002/cbic.201600285

Figure Lengend Snippet: Figure 5. Effects of pirfenidone and 4 on bleomycin-induced lung fibrosis in mice. A) Total lung collagen, B) Histological inflammatory score, C) Histological fibrosis score. Results represent the mean ± SEM of n=8 mice per group. (* P<0.03, **P<0.05, ***P<0.01 statistically different from bleomycin control). D) Representative Masson’s trichrome stained sections of mouse lung from uninjured saline control, bleomycin control and bleomycin treated with oral pirfenidone (200 mg/kg) or intratracheal 4 (500 µg/kg).

Article Snippet: Pirfenidone was purchased from Tocris Biochemicals and was dissolved in 0.5% carboxymethyl cellulose (Sigma Aldrich) to a concentration of 20 mg/mL.

Techniques: Control, Staining, Saline

Journal: Chembiochem : a European journal of chemical biology

Article Title: Galectin-3-Binding Glycomimetics that Strongly Reduce Bleomycin-Induced Lung Fibrosis and Modulate Intracellular Glycan Recognition.

doi: 10.1002/cbic.201600285

Figure Lengend Snippet: Figure 6. Effects of pirfenidone and compound 4 on BAL (bronchoalveolar lavage) fluid parameters in bleomycin-induced lung fibrosis in mice. Total protein measured by BCA reagent, MCP-1, and galectin-3 in BAL fluid and serum were measured by ELISA. Results represent the mean ± SEM of n=8 mice per group. (* P<0.05, statistically different from bleomycin control).

Article Snippet: Pirfenidone was purchased from Tocris Biochemicals and was dissolved in 0.5% carboxymethyl cellulose (Sigma Aldrich) to a concentration of 20 mg/mL.

Techniques: Enzyme-linked Immunosorbent Assay, Control

Journal: British Journal of Pharmacology

Article Title: A novel, orally active LPA 1 receptor antagonist inhibits lung fibrosis in the mouse bleomycin model

doi: 10.1111/j.1476-5381.2010.00828.x

Figure Lengend Snippet: AM966 demonstrates greater efficacy than pirfenidone after i.t. instillation of bleomycin. Mice were given intratracheal bleomycin sulfate (BLM; 3.0 units·kg−1) or saline vehicle (Veh.) followed by oral administration of AM966 (30 mg·kg−1, BID) or pirfenidone (20, 100 and 400 mg·kg−1, BID) for a period of 14 days. Representative (A, panels a–f.) Trichrome-stained images (100× magnification) of lungs from mice treated with (a) vehicle, (b) BLM, (c) BLM + AM966 (30 mg·kg−1, QD), (d) BLM + pirfenidone (20 mg·kg−1, BID), (e) BLM + pirfenidone (100 mg·kg−1, BID) and (f) BLM + pirfenidone (400 mg·kg−1, BID). (B) soluble collagen concentrations in BALF (C) Histopathological scoring of lung fibrosis (D) Percentage change in mouse body weight (E) total protein in BALF (F) LDH activity and (G) TIMP-1 concentration are also shown. Data represent the mean ± standard error of the mean of n = 4–6 mice per group. # denotes a significant increase (P < 0.05) compared to vehicle control. * denotes a significant decrease (P < 0.05) compared to BLM. QD, once a day; BID, twice a day; BALF, bronchoalveolar lavage fluid; LDH, lactate dehydrogenase; TIMP-1, tissue inhibitor of metalloproteinase-1.

Article Snippet: AM966 and pirfenidone (5-methyl-1-phenylpyridin-2-one) were synthesized at Amira Pharmaceuticals (San Diego, CA, USA).

Techniques: Saline, Staining, Activity Assay, Concentration Assay, Control