Mice with lipoprotein lipase deficiency showed more severe atherosclerotic lesions after 12 weeks on a Western-type diet compared to controls, indicating TRLs contribute to atherosclerosis.
Does induced whole-body lipoprotein lipase deficiency increase atherosclerosis in LDLR-deficient mice on a Western diet?
Intact, non-remnant triglyceride-rich lipoproteins contribute directly to atherosclerosis and vascular inflammation, challenging the widely accepted view that only remnant lipoproteins are atherogenic.
Absolute Event Rate: 0% vs 0%
Increased fasting and postprandial triglyceride levels are risk factors for cardiovascular disease (CVD). Partially metabolized triglyceride-rich lipoproteins (TRLs) termed remnants are created when intestinally-derived chylomicrons and liver secreted very low density lipoproteins (VLDLs) interact with lipoprotein lipase (LpL) situated on the luminal surface of capillary endothelial cells. Higher circulating remnant levels have been implicated as the reason for the relationship between TRL levels and CVD. We hypothesized that nascent lipoproteins not only remnants are atherogenic. To test this, we created mice with induced whole-body lipoprotein lipase (LpL) deficiency combined with LDL receptor (LDLR) deficiency. On an atherogenic Western-type diet (WD), male and female mice with induced global LpL deficiency (iLpl-/-) and LDLR knockdown (Ldlrkd) developed hypertriglyceridemia and elevated cholesterol levels; all the increased cholesterol was in chylomicrons or large VLDL. After 12 weeks on a WD, atherosclerotic lesions both in the brachiocephalic artery and the aortic root were more severe in iLpl-/-/Ldlrkd mice than control Ldlrkd mice. Aorta from hypertriglyceridemic mice had changes in the transcriptomes of endothelial cells, macrophages, and smooth muscle cells indicating vascular inflammation. Our data show that intact TRLs contribute to atherosclerosis, explain the association of postprandial lipemia and vascular disease and prove that non-remnant TRLs are not benign.
Cabodevilla et al. (Sat,) reported a other. Mice with lipoprotein lipase deficiency showed more severe atherosclerotic lesions after 12 weeks on a Western-type diet compared to controls, indicating TRLs contribute to atherosclerosis.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: