Regulation of Endothelial Lipase Expression

Hirata et al. [4] have noted that activated endothelial cells had increased endothelial lipase mRNA. Jaye et al. found that, upon stimulation with phorbol ester, the intensity of both 68 and 40 kDa bands increased in HCAEC and new bands of approximately 55 kDa, 38 and 36 kDa appeared in both HCAEC and HUVEC upon stimulation [3]. These new bands were not characterized, but may represent alternative splice products or an enzymatic cleavage product. Hirata et al. demonstrated that the expression of endothelial lipase is regulated by cytokines, by fluid shear stress and by cyclic stretch [18]. Using both HUVEC and HCAEC, they examined the effects of IL-1/ and TNF-a on endofhelial hpase mRNA levels. Exposure to IL-1/ for 24 h resulted in a 6.5-fold increase in EL mRNA in both HUVEC and HCAEC. TNF-a produced a ca. 4-fold increase in EL mRNA. The same group examined the response of both HUVEC and HCAEC to shear stress, and found a 2-3-fold increase in EL mRNA after 6 h of exposure. Additionally, cyclic stretch resulted in a 2.7-fold increase in EL mRNA. They concluded fhat EL expression is highly regulated by factors implicated in fhe development of vascular disease. 

The cytokine-induced increase in endofhelial lipase expression and secretion by endofhehal ceUs is in marked contrast to fhe effect of cytokines on hepatic hpase and Upoprotein hpase expression. Feingold et al. found that cytokines down-regu-late Upoprotein hpase [19] and hepatic lipase [20] expression. Both acute and chronic inflammatory conditions are associated with decreased HDL levels [21]. A decrease in HL levels in inflammatory states would be expected to increase HDL levels. These results support fhe possibihty fhat endothelial lipase has a significant role in regulating HDL levels, especiaUy in inflammatory states. 

HUVEC represents baseline expression, and PMA-stimulated cells serve as a positive control. 

---