Carboxyl Ester Lipase Expression in Macrophages Increases Cholesteryl Ester Accumulation and Promotes Atherosclerosis

Abstract

Carboxyl ester lipase (CEL, also called cholesterol esterase or bile salt-dependent lipase) is a lipolytic enzyme capable of hydrolyzing cholesteryl esters, triacylglycerols, and phospholipids in a trihydroxy bile salt-dependent manner but hydrolyzes ceramides and lysophospholipids via bile salt-independent mechanisms. Although CEL is synthesized predominantly in the pancreas, a low level of CEL expression was reported in human macrophages. This study used transgenic mice with macrophage CEL expression at levels comparable with that observed in human macrophages to explore the functional role and physiological significance of macrophage CEL expression. Peritoneal macrophages from CEL transgenic mice displayed a 4-fold increase in

Macrophage-specific transgenic expression of cholesteryl ester hydrolase significantly reduces atherosclerosis and lesion necrosis in Ldlr–/– mice

“…Li and Hui reported the absence of Hsl in human macrophages and demonstrated the expression of bile salt-stimulated CEH, similar to secretory pancreatic carboxyl ester lipase (Cel) (9). However, macrophage-specific transgenic expression of this Cel increased CE accumulation and promoted atherosclerosis (10), confirming the initial speculation of Li and Hui that a secretory enzyme such as Cel is unlikely to play a role in intracellular cholesterol metabolism and prevention of foam cell formation (9).…”

Transcriptional diversity during monocyte to macrophage differentiation

“…Additionally, genes important in the metabolism and transport of long chain fatty acids including FABP 3, 4, and 5, cholesterol 27-hydroxylase, which regulates the export of cholesterol [31], lipase A (LIPA) which promotes chylomicron formation and atherosclerosis [32], and HMGCR, the target of statins [33] were all up regulated in macrophages. LPL, which may contribute to foam cell formation and hydrolyzes triglycerides in chylomicrons, VLDL and HDL and lysosomal phospholipase A2, which is an independent risk factor of coronary heart disease [34] were also increased during macrophage differentiation.…”

Apolipoprotein E4 Impairs Macrophage Efferocytosis and Potentiates Apoptosis by Accelerating Endoplasmic Reticulum Stress

“…In Vitro Experiments with Peritoneal Macrophages-Peritoneal macrophages were obtained 3 days after intraperitoneal injection of a 4% thioglycollate solution as described (32). Peritoneal macrophages were plated overnight before use.…”