The journal of gene medicine · 2003
Pre-administration of angiopoietin-1 followed by VEGF induces functional and mature vascular formation in a rabbit ischemic model.
Сравнительное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Yamauchi Akihiko, Ito Yoshinori, Morikawa Masayuki, Kobune Masayoshi, Huang Jianhua, Sasaki Katsunori, Takahashi Kazuhiro, Nakamura Kiminori, Dehari Hironari, Niitsu Yoshiro, Abe Tomio, Hamada Hirofumi
Аннотация
BACKGROUND: Angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF) play important roles in vascular formation and maturation, suggesting that the combination of these two would be a promising therapy for ischemia. However, it remains unclear what the best schedule of administration of these cytokines might be.
METHODS: Six experimental groups were used to prepare the rabbit ischemic hindlimb model following naked plasmid intramuscular administration as follows: empty vector (C), single gene (Ang1, A; VEGF, V), Ang-1 followed by VEGF (A - V), co-administration of Ang1 and VEGF (A + V), and VEGF followed by Ang1 (V - A).
RESULTS: Thirty days after gene administration, A - V showed a significantly increased blood pressure and blood-flow recovery in the ischemic limb compared with the control group. Histological findings by alpha-smooth muscle-actin (alpha-SMA) staining revealed that the two combination groups had more mature vessels as compared with the control group. Significantly, A - V revealed the highest density of alpha-SMA-positive vessels compared with VEGF alone or Ang1 alone. Angiographic assessment revealed that A - V had a greater increased arterial diameter compared with VEGF alone. Edema, one of the major adverse effects induced by VEGF, was not found in A - V throughout the experiments, while VEGF alone and V - A showed severe edema induced by VEGF.
CONCLUSIONS: The pre-administration of Ang1 followed by VEGF resulted in an improvement of hemodynamic status, an increased number of vessels covered with alpha-actin-positive mural cells, and prevention of VEGF-mediated edema. Thus, priming by Ang1 gene administration would be beneficial for therapeutic angiogenesis in VEGF gene therapy.
METHODS: Six experimental groups were used to prepare the rabbit ischemic hindlimb model following naked plasmid intramuscular administration as follows: empty vector (C), single gene (Ang1, A; VEGF, V), Ang-1 followed by VEGF (A - V), co-administration of Ang1 and VEGF (A + V), and VEGF followed by Ang1 (V - A).
RESULTS: Thirty days after gene administration, A - V showed a significantly increased blood pressure and blood-flow recovery in the ischemic limb compared with the control group. Histological findings by alpha-smooth muscle-actin (alpha-SMA) staining revealed that the two combination groups had more mature vessels as compared with the control group. Significantly, A - V revealed the highest density of alpha-SMA-positive vessels compared with VEGF alone or Ang1 alone. Angiographic assessment revealed that A - V had a greater increased arterial diameter compared with VEGF alone. Edema, one of the major adverse effects induced by VEGF, was not found in A - V throughout the experiments, while VEGF alone and V - A showed severe edema induced by VEGF.
CONCLUSIONS: The pre-administration of Ang1 followed by VEGF resulted in an improvement of hemodynamic status, an increased number of vessels covered with alpha-actin-positive mural cells, and prevention of VEGF-mediated edema. Thus, priming by Ang1 gene administration would be beneficial for therapeutic angiogenesis in VEGF gene therapy.