Synthesis and secretion of the pancreatic-type carboxyl ester lipase by human endothelial cells.
Human aortic extracts contain significant cholesteryl ester hydrolytic activity. The enzymic activity was shown to be activated by trihydroxylated bile salt, but not by dihydroxylated bile salt. Monospecific antibodies prepared against rat pancreatic carboxyl ester lipase (CEL, cholesterol esterase) immunoprecipitated cholesteryl ester hydrolytic activity from human aorta, demonstrating that the neutral CEL in aorta is highly similar to and probably identical with the pancreatic enzyme. Reverse transcriptase PCR amplification of mRNA from human aortic endothelial cells revealed de novo synthesis of the pancreatic-type CEL by these cells. Preincubating human aortic endothelial cells with oxidized or native low-density lipoprotein resulted in an 8- and 3-fold increase in CEL activity secreted into the culture medium respectively. A potential physiological role for the endothelial CEL was demonstrated by studies showing its ability to confer partial protection against the cytotoxic effects of lysophosphatidylcholine. The protective effect of CEL is related to its bile-salt-independent lysophospholipase activity. However, CEL hydrolysis of lysophosphatidylcholine can be inhibited by excess cholesterol. Taken together, these results indicate that pancreatic-type CEL is synthesized by cells lining the vessel wall. Moreover, vascular CEL may interact with cholesterol and oxidized lipoproteins to modulate the progression of atherosclerosis.
Li
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Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, OH 45267-0529, USA.
Hui
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DY
D000818:Animals; D001011:Aorta; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000737:chemistry; D003603:Cytotoxins / Q000378:metabolism / Q000633:toxicity; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008244:Lysophosphatidylcholines / Q000378:metabolism / Q000633:toxicity; D010179:Pancreas / Q000201:enzymology*; D012313:RNA / Q000302:isolation & purification; D051381:Rats; D014471:Umbilical Veins
D002788:Cholesterol Esters; D017077:Culture Media, Conditioned; D003603:Cytotoxins; D008244:Lysophosphatidylcholines; D012313:RNA; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase