Serum amyloid a activation of inflammatory and adhesion molecules inhuman coronary artery and umbilicalvein endothelial cells

Inflammation is considered to be the driving force leading to atherogenic and atherosclerotic mechanisms. Increased levels of SAA predict the risk of coronary artery disease and even mortality from cardiovascular disease in humans. Recent animal and human studies have indicated that SAA plays a causal role in atherogenesis, although it is largely unclear how this occurs. The objectives of this study are to understand the role of SAA in activating possible atherogenic inflammatory responses in human coronary artery endothelial cells (HCAEC) and to compare them with human umbilical vein endothelial cells (HUVEC). Our hypothesis is that vein and artery endothelial cells have different expression patterns and levels, leading to differential inflammatory responses. HUVEC and HCAEC were grown in order to analyze the effects of SAA on endothelial expression of pro-inflammatory cytokines, such as IL-6, chemokines, such as IL-8, and adhesion molecules (s-ICAM, s-VCAM, E-selectin) by reverse transcription-PCR and ELISAs. We compared the dose responses of SAA between HUVEC and HCAEC. SAA activated both HUVEC and HCAEC pro-inflammatory factors in a dose-dependent manner. In comparison however, HCAEC showed a strikingly greater sensitivity to SAA, with a higher level of expression of all pro-inflammatory markers at much lower concentrations of SAA, and their much greater stimulation at higher SAA concentrations. SAA also generated a dose-dependent positive feedback response on its own mRNA expression in HCAEC as compared to HUVEC. In summary, there are distinct significant differences in the levels of inflammatory markers and adhesion molecules between HUVEC and HCAEC SAA induced dose responses that could potentially account for HCAEC greater susceptibility to inflammation and atherogenesis.