Deletion of phd2 in myeloid lineage attenuates hypertensive cardiovascular remodeling.
Jiro Ikeda, Toshihiro Ichiki, Hirohide Matsuura, Eriko Inoue, Junji Kishimoto, Aya Watanabe, Chikahiro Sankoda, Shiro Kitamoto, Tomotake Tokunou, Kotaro Takeda, Guo-Hua Fong, Kenji Sunagawa
J Am Heart Assoc | Ovid Technologies (Wolters Kluwer Health) | Published : 2013
BACKGROUND: Hypertension induces cardiovascular hypertrophy and fibrosis. Infiltrated macrophages are critically involved in this process. We recently reported that inhibition of prolyl hydroxylase domain protein 2 (PHD2), which hydroxylates the proline residues of hypoxia-inducible factor-α (HIF-α) and thereby induces HIF-α degradation, suppressed inflammatory responses in macrophages. We examined whether myeloid-specific Phd2 deletion affects hypertension-induced cardiovascular remodeling. METHODS AND RESULTS: Myeloid-specific PHD2-deficient mice (MyPHD2KO) were generated by crossing Phd2-floxed mice with LysM-Cre transgenic mice, resulting in the accumulation of HIF-1α and HIF-2α in macro..View full abstract