TY - JOUR
T1 - Carriers of the frequent lipoprotein lipase S447X variant exhibit enhanced postprandial apoprotein B-48 clearance
AU - Nierman, Melchior C.
AU - Rip, Jaap
AU - Kuivenhoven, Jan-Albert
AU - van Raalte, Daniel H.
AU - Hutten, Barbara A.
AU - Sakai, Naohiko
AU - Kastelein, John J. P.
AU - Stroes, Erik S. G.
PY - 2005
Y1 - 2005
N2 - The frequent lipoprotein lipase S447X variant (LPLS447X) is firmly associated with a lower incidence of cardiovascular disease, the mechanisms for which remain to be established. To further unravel these beneficial effects, we studied the consequences of LPLS447X heterozygosity on LPL mass and activity, as well as on the postprandial lipoprotein profile. Fifteen male heterozygous LPLS447X carriers and 15 matched control subjects received an oral fat load (30 g/m2). Lipid parameters were evaluated at baseline and 2, 3, 4, and 6 hours after fat loading. LPL concentration and activity were analyzed, and endothelial function was evaluated noninvasively as flow-mediated dilation of the brachial artery. Although baseline apoprotein B-48 (apoB48) levels were similar, the rise in apoB48 was attenuated in LPLS447X carriers with 25% lower peak values compared with controls (P = .04). In conjunction, LPLS447X carriers were characterized by a 2.4-fold increase in preheparin LPL mass (P < .0001). The decrease in postprandial flow-mediated dilation was comparable in both groups. LPLS447X carriers exhibit enhanced apoB48 clearance with concomitant increase in preheparin LPL mass, without changes in LPL activity. This combination might suggest a role for increased ligand action of LPL in LPLS447X carriers contributing to the cardiovascular protection in carriers of this mutation. © 2005 Elsevier Inc. All rights reserved.
AB - The frequent lipoprotein lipase S447X variant (LPLS447X) is firmly associated with a lower incidence of cardiovascular disease, the mechanisms for which remain to be established. To further unravel these beneficial effects, we studied the consequences of LPLS447X heterozygosity on LPL mass and activity, as well as on the postprandial lipoprotein profile. Fifteen male heterozygous LPLS447X carriers and 15 matched control subjects received an oral fat load (30 g/m2). Lipid parameters were evaluated at baseline and 2, 3, 4, and 6 hours after fat loading. LPL concentration and activity were analyzed, and endothelial function was evaluated noninvasively as flow-mediated dilation of the brachial artery. Although baseline apoprotein B-48 (apoB48) levels were similar, the rise in apoB48 was attenuated in LPLS447X carriers with 25% lower peak values compared with controls (P = .04). In conjunction, LPLS447X carriers were characterized by a 2.4-fold increase in preheparin LPL mass (P < .0001). The decrease in postprandial flow-mediated dilation was comparable in both groups. LPLS447X carriers exhibit enhanced apoB48 clearance with concomitant increase in preheparin LPL mass, without changes in LPL activity. This combination might suggest a role for increased ligand action of LPL in LPLS447X carriers contributing to the cardiovascular protection in carriers of this mutation. © 2005 Elsevier Inc. All rights reserved.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=27344447849&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/16253639
U2 - https://doi.org/10.1016/j.metabol.2005.05.016
DO - https://doi.org/10.1016/j.metabol.2005.05.016
M3 - Article
C2 - 16253639
SN - 0026-0495
VL - 54
SP - 1499
EP - 1503
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 11
ER -