Background:
Due to the development of pulmonary arterial hypertension (PAH), distal pulmonary artery endothelial cells (dPAEC) are exposed to wall shear stress (SS) that is different in physical characteristics compared to normal condition. The effect of individual components of SS on PAEC biology has not been thoroughly examined. Thus the current study was designed to examine how dPAEC respond to different component of SS in regarding to gene expression including adhesion molecules: ICAM, VCAM, E-selectin; chemokine: MCP-1 and growth factors:VEGF, Flt-1.
Methods:
Bovine dPAEC were cultured and placed on fibronectin-coated slides till confluent. Cells were then exposed to SS with different frequency (1Hz, 2Hz), pulsation (low, medium and high with an average SS of 14 dynes/cm
2
) and time (1hr or 6hrs). The flow studies were carried out using a flow chamber connected to a variable speed flow pump. All data was represented as fold change relative to static condition.
Results:
As shown in table
below,
The effect of flow frequency on gene expression depends on individual gene. There was no difference of ICAM expression between 1Hz and 2Hz. Frequency of 2Hz significantly increased VCAM and MCP-1 expression compared to frequency of 1Hz.
Compared to static condition, steady flow increased all gene expression. One hour pulsatile flow further increased ICAM, VCAM, E-selectin and MCP-1 but not VEGF or Flt-1 expression as pulsation increased. 3) Prolonged pulsatile flow further increased all gene expression.
Conclusion:
Physical characteristics of flow, especially flow pulsation stimulate dPAEC gene expression which can contribute to the development of PAH.
Glucocorticoids Downregulate Cyclooxygenase-1 Gene Expression and Prostacyclin Synthesis in Fetal Pulmonary Artery Endothelium
