Captopril mitigates splenomegaly and myelofibrosis in the Gata1low murine model of myelofibrosis

Figures

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  Figure 1. Effects of captopril administration on Gata1 low mouse model of myelofibrosis. Wild‐type (wt) or Gata1 low mice were treated from 10 to 12 mo with either captopril 72 mg/kg/d or vehicle in drinking water. Mice were killed at 13 mo, and tissues were harvested. (A) Haematoxylin and eosin staining of bone marrow from the humeri of the three mouse cohorts. Magnification is 40×. (B, C) Gomori staining of the same histological sections shows reticulin deposition in vehicle‐treated Gata1 low mice. Under blinded conditions, a board‐certified pathologist (T.A.S.) scored bone marrow for reticulin. Captopril treatment resulted in decreased reticulin fibre score, with *P value < .05 (one‐tailed Mann‐Whitney test). (D) Haematoxylin and eosin staining of spleens from the three mouse cohorts. Magnification is 60×. (E) Gomori staining of the same histological sections shows reticulin deposition in vehicle‐treated Gata1 low mice. (F) Spleens from the three mouse cohorts were weighed, with *P value < .05

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  Figure 2. Effects of captopril administration on peripheral blood counts. Wild‐type (wt) or Gata1 low mice were treated from 10 to 12 mo with either captopril 72 mg/kg/d or vehicle in drinking water. Mice were killed at 13.5 mo, and tissues were harvested. Complete blood cell counts with differentials were obtained. (A) white blood cells (WBC); (B) lymphocytes; (C) eosinophils; (D) neutrophils; (E) platelets; and (F) red blood cells (RBC). Means are indicated; *indicates P < .05

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  Figure 3. Effects of captopril administration of megakaryocytes and collagen. Wild‐type (wt) or Gata1 low mice were treated from 10 to 12 mo with either captopril 72 mg/kg/d or vehicle in drinking water. Mice were killed at 13.5 mo, and tissues were harvested. (A) Flow cytometric analysis was performed on femur bone marrow cells to measure percentage of CD45+ cells expressing CD41+ cells. Representative FACS data are presented for wt, Gata1 low‐untreated mice and Gata1 low captopril‐treated mice. (B‐E) qPCR of mRNA isolated from bone marrow of Gata1 low mice treated ± captopril, as described above. Interrogated transcripts were CD41, CD61, Col 1a and Col 3a. Data show Gata1 low qPCR transcript levels from untreated mice compared to the ratio of Gata1 low transcript levels from mice treated with captopril relative to Gata1 low‐untreated mice. *P value .05. (F) Flow cytometric analysis was performed on spleen‐derived cells to measure percentage of CD45+ cells expressing CD41+ cells. Representative FACS data are presented for wt, Gata1 low‐untreated mice and Gata1 low captopril‐treated mice. (G‐J) qPCR of mRNA isolated from spleens of Gata1 low mice treated ± captopril, as described above.…