Figure 4.

Impaired vascular repair in Hif1a^f/f/Tie2Cre⁺ (CKO) mouse lungs was not ascribed to HIF-1α deficiency in bone marrow (BM) cells. A: Quantitative PCR analysis demonstrating >95% efficiency of bone marrow reconstitution. Bone marrow cells from wild-type (WT) female mice were transplanted to lethally irradiated Hif1a^f/f/Tie2Cre⁺ male mice. Six weeks after transplantation, bone marrow samples from these chimeric male mice and WT male mice [positive control (Ctl)] were isolated for genomic DNA isolation and PCR analysis of Y-chromosome–specific gene Sry. B: Defective vascular repair in lungs of Hif1a^f/f/Tie2Cre⁺ mice transplanted with bone marrow cells from either Hif1α WT (BM^+/+) or CKO (BM^−/−) mice. At 6 weeks after bone marrow cell transplantation, the mice were challenged with cecal ligation and puncture (CLP). At 72 hours after CLP, lung tissues were collected for transvascular Evans Blue Dye–conjugated albumin (EBA) flux measurement. C: Lung myeloperoxidase (MPO) activity measurement (72 hours after CLP). D–G: Real-time quantitative RT-PCR analysis demonstrating increased expression of proinflammatory mediators in Hif1a^f/f/Tie2Cre⁺ mouse lungs reconstituted with either WT or CKO bone marrow cells at 72 hours after CLP challenge. Data are expressed as means ± SD (A and D–G) or means (B and C). n = 4 mice per group (A and D–G). Icam-1, intercellular adhesion molecule 1; Nos-2, inducible nitric oxide synthase; Tnf-α, tumor necrosis factor–α.