Apoptosis in vascular endothelial cells caused by serum deprivation, oxidative stress and transforming growth factor-beta

Endothelium. 1999;7(1):35-49. doi: 10.3109/10623329909165310.

Abstract

Vascular endothelial cell apoptosis has previously been shown to play a role in the pathogenesis of hypertension-induced vessel deletion and damage. In the present in vitro study we analyse several possible relevant causative factors of vascular endothelial cell apoptosis, namely, serum deprivation and nutrient depletion, oxidative stress in the forms of hypoxia, hyperoxia or free radical damage, and altered levels of transforming growth factor-beta1 (TGF-beta1) protein. An established cell line, bovine aortic endothelial cells (BAEC), was maintained in complete growth medium (RPMI-1640 plus 15% fetal calf serum and antibiotics, abbreviated as RPMI) in 25cm2 flasks or in 12-well plates on glass coverslips. Confluent but actively-growing cultures were treated with either hypoxia (PO2 of RPMI = 50mmHg), serum-free media (SFM), SFM plus hypoxia, hyperoxia (PO2 of RPMI = 450mmHg), hydrogen peroxide (H2O2, 1mM) in SFM, or TGF-beta1 protein (10ng/mL) in SFM. Appropriate control cultures were used. BAEC were collected 48h or 72h after all treatments except for TGF-beta1 and H2O2 treatments that were collected at 16-18h. Cell death was assessed using morphological characteristics or in situ end labeling (ISEL), cell proliferation assessed using proliferating cell nuclear antigen (PCNA), and TGF-beta1 expression assessed using transcript levels or immunohistochemistry. All treatments significantly increased levels of apoptosis over control cultures (P<0.05), and decreased levels of cell proliferation. Treatment with TGF-beta1 protein or SFM plus hypoxia induced greatest levels of apoptosis. TGF-beta1 protein and transcript levels were decreased in treated cultures, results suggesting that a paracrine source of TGF-beta1 protein would be needed as a cause of endothelial cell apoptosis in viva. Future therapies against inappropriate vessel deletion in disease states may use the known gene-driven nature of apoptosis to modify this sort of cell death in endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cattle
  • Cell Line
  • Cell Size
  • Culture Media, Serum-Free / pharmacology*
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / physiopathology*
  • Endothelium, Vascular / ultrastructure
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Microscopy, Electron
  • Mitosis / drug effects
  • Oxidative Stress / physiology*
  • Polymerase Chain Reaction
  • Proliferating Cell Nuclear Antigen / analysis
  • Staining and Labeling
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Culture Media, Serum-Free
  • Proliferating Cell Nuclear Antigen
  • Transforming Growth Factor beta