RESUMO
Bone marrow- (BM-) derived cells can differentiate into smooth muscle-like cells (SMLC), resulting in vascular pathogenesis. However, the molecular mechanism of the differentiation remains unknown. We have recently reported that Notch signaling promotes while a Notch target HERP1 inhibit the differentiation of mesenchymal cells to SMC. During the differentiation of BM-derived mononuclear cells into smooth muscle alpha-actin (SMA)-positive cells, expression of Jagged1 and SMC-specific Notch3 was increased. Blocking Notch with gamma-secretase inhibitor prevented the induction of SMA. Wire-mediated vascular injury was produced in femoral arteries in mice transplanted with green fluorescent protein (GFP)-positive cells. Many double-positive cells for GFP/Jagged1 or GFP/Notch3 were detected in the thickened neointima. In contrast, only a few SMA-positive cells were positive for GFP in neointima where HERP1, a suppressor for Notch, were abundantly expressed. In conclusion, Notch-HERP1 pathway plays an important role in differentiation of BM-derived mononuclear cells into SMLC.
Assuntos
Artérias/lesões , Artérias/patologia , Células da Medula Óssea/patologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Proteínas Proto-Oncogênicas/metabolismo , Receptores Notch/metabolismo , Animais , Artérias/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese , Células da Medula Óssea/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Diferenciação Celular , Células Cultivadas , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteína Jagged-1 , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Receptor Notch3 , Receptor Notch4 , Proteínas Repressoras/biossíntese , Proteínas Serrate-Jagged , Transdução de Sinais , Túnica Íntima/lesões , Túnica Íntima/metabolismo , Túnica Íntima/patologiaRESUMO
A 22-year-old man presented with renovascular hypertension, based on a stenosis of the distal portion of the right renal artery with a "string of beads"-like appearance. An intravascular ultrasound image at the renal artery lesion revealed irregularity of the vascular wall. Directional atherectomy was performed and histopathology of atherectomised tissues showed medial fibroplasia, a common type of fibromuscular dysplasia. After atherectomy his hypertension was markedly improved. We report here a case of renovascular hypertension due to fibromuscular dysplasia, successfully diagnosed and treated with IVUS-guided renal atherectomy.
Assuntos
Aterectomia/métodos , Displasia Fibromuscular/complicações , Hipertensão Renovascular/etiologia , Hipertensão Renovascular/cirurgia , Ultrassonografia de Intervenção , Adulto , Angiografia , Humanos , Masculino , Artéria Renal/diagnóstico por imagem , Artéria Renal/patologia , Artéria Renal/cirurgiaRESUMO
Neurotrophins play an essential role in nerve systems. Recent reports indicated that neurotrophins [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5)] have numerous effects on non-neural cells, especially on immune cells. However, whether lung cells express neurotrophins and/or their receptors (TrkA for NGF, TrkB for BDNF and NT-4/5, and TrkC for NT-3) has never been systematically investigated. We investigated constitutive expression of neurotrophin family and their Trk receptor family in alveolar macrophages and other peripheral lung cells of mice. New findings were: (1) RT-PCR for neurotrophins and their receptors detected NT-3 and NT-4/5 in alveolar macrophages, BDNF, NT-4/5, trkA, the truncated form of trkB, and trkC in lung homogenate, but no trks in alveolar macrophages, (2) immunohistochemistry for neurotrophin receptors detected TrkA in capillary cells, the truncated form of TrkB, and TrkC in interstitial macrophages, (3) immunoelectron microscopy for TrkC revealed expression of TrkC on the surface of interstitial macrophages, and (4) in situ hybridization for neurotrophins detected BDNF in interstitial macrophages and alveolar type I cells, NT-3 in alveolar macrophages, and NT-4/5 in alveolar and interstitial macrophages. These findings indicate that a previously unknown signal trafficking occurs through neurotrophins in peripheral lung.