Reduced cyclic stretch, endothelial dysfunction, and oxidative stress: an ex vivo model
Received 9 January 2009; received in revised form 23 June 2009; accepted 30 June 2009. published online 07 September 2009.
Abstract
Background
The objective of this study was to investigate whether reduction of cyclic circumferential stretch will impair endothelial function and elevate basal levels of oxidative stress, both known risk factors linked to cardiovascular disease.
Methods
Ex vivo and in vitro models were used to perfuse porcine carotid arteries and porcine endothelial cells, respectively, for 24 h. In both cases, one group was allowed to stretch naturally when exposed to a pulse shear stress (6±3 dynes/cm2) combined with a pulse pressure of 80±10 mmHg, yielding a physiological cyclic stretch of 4–5%. This group was compared to a reduced stretch group, achieved by wrapping the arterial segment with a silicon band or by seeding the endothelial cells inside less compliant tubes, decreasing cyclic stretch to 1%.
Results
The experimentally reduced compliance caused a significant decrease in bradykinin-dependent vascular relaxation. Reduced compliance significantly decreased the phosphorylation of serine 1177 (Ser1177) on eNOS, suggesting the activity of eNOS was decreased. Overall production of reactive oxygen species was increased by reducing compliance, as visualized with DHE. Finally, p22-phox and p47-phox, key players in the superoxide-generating NAD(P)H oxidase, were also up-regulated by reduced compliance.
Conclusions
These findings point out how reduced arterial compliance increases the risk of arterial disease by creating a less functional endothelium, interrupting the eNOS activation pathway, and increasing the vascular levels of oxidative stress.
ABSTRACT