Vascular remodeling is a key feature of many pathologic states, including a
therosclerosis, or hypertension. Vascular smooth muscle cells participate i
n determining the vessel structure by several mechanisms such as cell migra
tion, cell growth, or cell death (necrosis or apoptosis). Here we report th
at thapsigargin, an inhibitor of endoplasmic reticulum Ca2+-adenosine triph
osphatase (ATPase), is able to induce apoptosis in human vascular smooth mu
scle cells (HVSMCs). Apoptosis was assessed by three different methods: dif
ferential chromatin binding dye staining, cytoplasmic histone-associated DN
A fragments detection by enzyme-linked immunosorbent assay (ELISA) and term
inal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNE
L). When HVSMCs were treated for 1 h with thapsigargin (100 nM-10 muM), the
re was a concentration-dependent increase in both parameters 24 h after the
thapsigargin pulse, When a time-course experiment was performed, both para
meters were significantly enhanced from 3 to 6 h after the exposure to thap
sigargin. We conclude that thapsigargin promotes apoptosis in HVSMCs, provi
ding a useful tool for the study of programmed cell death in human vascular
smooth muscle.