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Reduced NGF in Gastric Endothelial Cells Is One of the Main Causes of Impaired Angiogenesis in Aging Gastric Mucosa. | LitMetric

Reduced NGF in Gastric Endothelial Cells Is One of the Main Causes of Impaired Angiogenesis in Aging Gastric Mucosa.

Cell Mol Gastroenterol Hepatol

Medical and Research Services, Veterans Affairs Long Beach Healthcare System, Long Beach, California.

Published: May 2018

AI Article Synopsis

  • Aging gastric mucosa is more susceptible to injury and heals more slowly due to reduced angiogenesis, potentially linked to a lack of nerve growth factor (NGF) in gastric endothelial cells (ECs).
  • NGF expression and angiogenesis were significantly lower in aging gastric endothelial cells compared to younger cells, and NGF treatment enhanced both angiogenesis and ulcer healing in aging rat models.
  • In humans, NGF levels in gastric mucosal vessels were also significantly lower in older individuals, indicating that NGF deficiency may play a crucial role in impaired healing as we age.

Article Abstract

Background & Aims: Aging gastric mucosa has increased susceptibility to injury and delayed healing owing to impaired angiogenesis, but the mechanisms are not fully known. We examined whether impairment of angiogenesis in aging gastric mucosa is caused by deficiency of nerve growth factor (NGF) in gastric endothelial cells (ECs), and whether NGF therapy could reverse this impairment.

Methods: In gastric mucosal ECs (GECs) isolated from young and aging rats we examined the following: (1) in vitro angiogenesis, (2) NGF expression, and (3) the effect of NGF treatment on angiogenesis, GEC proliferation and migration, and dependence on serum response factor. In in vivo studies in young and aging rats, we examined NGF expression in gastric mucosa and the effect of NGF treatment on angiogenesis and gastric ulcer healing. To determine human relevance, we examined NGF expression in gastric mucosal biopsy specimens of aging (≥70 y) and young (≤40 y) individuals.

Results: In cultured aging GECs, NGF expression and angiogenesis were reduced significantly by 3.0-fold and 4.1-fold vs young GECs. NGF therapy reversed impairment of angiogenesis in aging GECs, and serum response factor silencing completely abolished this response. In gastric mucosa of aging rats, NGF expression in GECs was reduced significantly vs young rats. In aging rats, local NGF treatment significantly increased angiogenesis and accelerated gastric ulcer healing. In aging human subjects, NGF expression in ECs of gastric mucosal vessels was 5.5-fold reduced vs young individuals.

Conclusions: NGF deficiency in ECs is a key mechanism underlying impaired angiogenesis and delayed ulcer healing in aging gastric mucosa. Local NGF therapy can reverse these impairments.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037903PMC
http://dx.doi.org/10.1016/j.jcmgh.2018.05.003DOI Listing

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