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Kumari A, Kristensen KK, Ploug M, et al. The Importance of Lipoprotein Lipase Regulation in Atherosclerosis. Biomedicines. 2021;9(7)doi: 10.3390/biomedicines9070782.
Kumari, A., Kristensen, K. K., Ploug, M., & Winther, A. L. (2021). The Importance of Lipoprotein Lipase Regulation in Atherosclerosis. Biomedicines, 9(7), . https://doi.org/10.3390/biomedicines9070782
Kumari, Anni, et al. "The Importance of Lipoprotein Lipase Regulation in Atherosclerosis." Biomedicines vol. 9,7 (2021). doi: https://doi.org/10.3390/biomedicines9070782
Kumari A, Kristensen KK, Ploug M, Winther AL. The Importance of Lipoprotein Lipase Regulation in Atherosclerosis. Biomedicines. 2021 Jul 06;9(7). doi: 10.3390/biomedicines9070782. PMID: 34356847; PMCID: PMC8301479.
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Biomedicines. 2021 Jul 06;9(7). doi: 10.3390/biomedicines9070782.

The Importance of Lipoprotein Lipase Regulation in Atherosclerosis.

Biomedicines

Anni Kumari, Kristian K Kristensen, Michael Ploug, Anne-Marie Lund Winther

Affiliations

  1. Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen N, Denmark.
  2. Biotech Research and Innovation Centre (BRIC), University of Copenhagen, DK-2200 Copenhagen N, Denmark.

PMID: 34356847 PMCID: PMC8301479 DOI: 10.3390/biomedicines9070782

Abstract

Lipoprotein lipase (LPL) plays a major role in the lipid homeostasis mainly by mediating the intravascular lipolysis of triglyceride rich lipoproteins. Impaired LPL activity leads to the accumulation of chylomicrons and very low-density lipoproteins (VLDL) in plasma, resulting in hypertriglyceridemia. While low-density lipoprotein cholesterol (LDL-C) is recognized as a primary risk factor for atherosclerosis, hypertriglyceridemia has been shown to be an independent risk factor for cardiovascular disease (CVD) and a residual risk factor in atherosclerosis development. In this review, we focus on the lipolysis machinery and discuss the potential role of triglycerides, remnant particles, and lipolysis mediators in the onset and progression of atherosclerotic cardiovascular disease (ASCVD). This review details a number of important factors involved in the maturation and transportation of LPL to the capillaries, where the triglycerides are hydrolyzed, generating remnant lipoproteins. Moreover, LPL and other factors involved in intravascular lipolysis are also reported to impact the clearance of remnant lipoproteins from plasma and promote lipoprotein retention in capillaries. Apolipoproteins (Apo) and angiopoietin-like proteins (ANGPTLs) play a crucial role in regulating LPL activity and recent insights into LPL regulation may elucidate new pharmacological means to address the challenge of hypertriglyceridemia in atherosclerosis development.

Keywords: ANGPTL; atherosclerosis; lipoprotein lipase

References

  1. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5296-300 - PubMed
  2. Biochem Biophys Res Commun. 2012 Aug 24;425(2):138-43 - PubMed
  3. J Lipid Res. 2017 Jun;58(6):1166-1173 - PubMed
  4. Sci Rep. 2015 Dec 21;5:18502 - PubMed
  5. J Lipid Res. 2013 Dec;54(12):3481-90 - PubMed
  6. J Lipid Res. 2010 Jun;51(6):1535-45 - PubMed
  7. J Clin Invest. 1999 Jun;103(12):1697-705 - PubMed
  8. Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13841-6 - PubMed
  9. Circulation. 2007 Jan 30;115(4):450-8 - PubMed
  10. J Biol Chem. 2003 Jun 20;278(25):23027-35 - PubMed
  11. J Biol Chem. 1992 Dec 15;267(35):25086-91 - PubMed
  12. J Lipid Res. 2016 Sep;57(9):1670-83 - PubMed
  13. J Biol Chem. 2004 Jul 2;279(27):27941-7 - PubMed
  14. J Biol Chem. 1994 Mar 25;269(12):8653-8 - PubMed
  15. J Biol Chem. 2018 Sep 7;293(36):14134-14145 - PubMed
  16. FEBS Lett. 1976 Jun 15;65(3):354-7 - PubMed
  17. J Clin Invest. 2009 Jan;119(1):70-9 - PubMed
  18. J Biol Chem. 2002 Mar 1;277(9):7405-11 - PubMed
  19. J Biol Chem. 2000 Sep 15;275(37):28488-93 - PubMed
  20. Nutrients. 2013 Mar 22;5(3):981-1001 - PubMed
  21. Proc Natl Acad Sci U S A. 2018 Jun 26;115(26):E6020-E6029 - PubMed
  22. J Lipid Res. 1994 Nov;35(11):2049-59 - PubMed
  23. J Clin Lipidol. 2016 Mar-Apr;10(2):394-409 - PubMed
  24. Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6319-6328 - PubMed
  25. Atherosclerosis. 2012 Sep;224(1):75-83 - PubMed
  26. J Lipid Res. 2020 May;61(5):591 - PubMed
  27. J Am Coll Cardiol. 2017 Sep 26;70(13):1637-1646 - PubMed
  28. Circ Cardiovasc Genet. 2010 Apr;3(2):169-78 - PubMed
  29. J Biol Chem. 2010 Sep 3;285(36):27561-70 - PubMed
  30. Science. 2008 Dec 12;322(5908):1702-5 - PubMed
  31. Biochem Biophys Res Commun. 2002 Aug 2;295(5):1156-9 - PubMed
  32. Biochim Biophys Acta. 2012 May;1821(5):833-42 - PubMed
  33. J Lipid Res. 2020 Sep;61(9):1271-1286 - PubMed
  34. J Biol Chem. 1992 Feb 25;267(6):4161-5 - PubMed
  35. J Biol Chem. 1997 Feb 28;272(9):5821-7 - PubMed
  36. Cell Metab. 2014 Sep 2;20(3):458-70 - PubMed
  37. J Lipid Res. 2019 Apr;60(4):783-793 - PubMed
  38. Arterioscler Thromb Vasc Biol. 2007 Mar;27(3):571-7 - PubMed
  39. N Engl J Med. 2017 Jul 20;377(3):211-221 - PubMed
  40. J Lipid Res. 2019 Oct;60(10):1741-1754 - PubMed
  41. Arterioscler Thromb Vasc Biol. 2011 Jan;31(1):176-82 - PubMed
  42. J Biol Chem. 2000 Aug 25;275(34):26293-9 - PubMed
  43. Curr Atheroscler Rep. 2012 Feb;14(1):1-10 - PubMed
  44. Biochemistry. 2000 Jul 18;39(28):8276-83 - PubMed
  45. J Lipid Res. 2011 Feb;52(2):189-206 - PubMed
  46. J Biol Chem. 1993 May 5;268(13):9369-75 - PubMed
  47. J Clin Invest. 2001 May;107(9):1183-92 - PubMed
  48. J Biol Chem. 1989 Jan 25;264(3):1473-82 - PubMed
  49. Biochem Biophys Res Commun. 1992 Jun 15;185(2):582-7 - PubMed
  50. Arterioscler Thromb Vasc Biol. 2000 Sep;20(9):E53-62 - PubMed
  51. Biochem Biophys Res Commun. 1970 Oct 9;41(1):57-62 - PubMed
  52. Biochemistry. 2007 Mar 27;46(12):3896-904 - PubMed
  53. BMJ. 2020 Oct 12;371:m3109 - PubMed
  54. J Lipid Res. 2017 Jan;58(1):216-225 - PubMed
  55. J Biol Chem. 2002 May 10;277(19):17281-90 - PubMed
  56. Nat Genet. 2007 Dec;39(12):1483-7 - PubMed
  57. Sci Transl Med. 2020 Jan 29;12(528): - PubMed
  58. J Biol Chem. 2002 Sep 13;277(37):33742-8 - PubMed
  59. Nature. 1992 Sep 10;359(6391):159-62 - PubMed
  60. Biochim Biophys Acta. 1982 Nov 12;713(2):292-9 - PubMed
  61. J Lipid Res. 2003 Jun;44(6):1216-23 - PubMed
  62. J Lipid Res. 1992 Jul;33(7):995-1003 - PubMed
  63. Nat Rev Cardiol. 2015 Oct;12(10):565-75 - PubMed
  64. Circ Res. 2016 Feb 19;118(4):547-63 - PubMed
  65. Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1723-1732 - PubMed
  66. Science. 2001 Oct 5;294(5540):169-73 - PubMed
  67. J Biol Chem. 1999 May 14;274(20):14170-5 - PubMed
  68. Arterioscler Thromb Vasc Biol. 2009 Jun;29(6):969-74 - PubMed
  69. Arterioscler Thromb Vasc Biol. 2005 Dec;25(12):2573-9 - PubMed
  70. J Biol Chem. 1993 Jul 15;268(20):15048-55 - PubMed
  71. J Lipid Res. 1996 Aug;37(8):1733-42 - PubMed
  72. J Am Coll Cardiol. 2017 Apr 25;69(16):2054-2063 - PubMed
  73. Science. 1983 Jul 8;221(4606):167-9 - PubMed
  74. J Biol Chem. 1994 Feb 11;269(6):4626-33 - PubMed
  75. Atherosclerosis. 2007 Nov;195(1):e9-16 - PubMed
  76. J Biol Chem. 2004 Nov 26;279(48):49964-72 - PubMed
  77. J Lipid Res. 2007 Feb;48(2):288-98 - PubMed
  78. J Lipid Res. 1997 Feb;38(2):301-14 - PubMed
  79. Nature. 2002 Jun 13;417(6890):750-4 - PubMed
  80. Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2504-9 - PubMed
  81. Circ Res. 2008 Aug 29;103(5):450-3 - PubMed
  82. J Inherit Metab Dis. 2012 May;35(3):531-40 - PubMed
  83. J Biol Chem. 2003 Feb 28;278(9):7344-9 - PubMed
  84. ACS Chem Biol. 2021 Mar 19;16(3):457-462 - PubMed
  85. Circulation. 2018 Feb 27;137(9):975-977 - PubMed
  86. J Biol Chem. 2010 Dec 10;285(50):39239-48 - PubMed
  87. J Biol Chem. 1974 Aug 25;249(16):5308-13 - PubMed
  88. Science. 1990 Aug 17;249(4970):790-3 - PubMed
  89. Curr Opin Lipidol. 2012 Jun;23(3):206-12 - PubMed
  90. J Lipid Res. 2021 Mar 23;62:100071 - PubMed
  91. J Biol Chem. 2003 Sep 5;278(36):34438-44 - PubMed
  92. Circulation. 1999 Jun 8;99(22):2901-7 - PubMed
  93. J Biol Chem. 2020 Jun 19;295(25):8628-8635 - PubMed
  94. BMJ. 2009 Feb 16;338:b92 - PubMed
  95. J Manag Care Pharm. 2013 Mar;19(2):139-49 - PubMed
  96. Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19751-6 - PubMed
  97. Arterioscler Thromb. 1994 Nov;14(11):1767-74 - PubMed
  98. Dev Cell. 2019 Nov 4;51(3):387-398.e4 - PubMed
  99. J Biol Chem. 1997 Jan 10;272(2):766-72 - PubMed
  100. Biochem Biophys Res Commun. 2012 Aug 10;424(4):786-92 - PubMed
  101. Neth Heart J. 2017 Apr;25(4):231-242 - PubMed
  102. Nat Rev Cardiol. 2016 Jan;13(1):48-60 - PubMed
  103. PLoS One. 2010 Nov 10;5(11):e13919 - PubMed
  104. J Lipid Res. 2020 Aug;61(8):1203-1220 - PubMed
  105. Biochem Biophys Res Commun. 1975 Oct 27;66(4):1467-75 - PubMed
  106. Arterioscler Thromb Vasc Biol. 1995 Apr;15(4):534-42 - PubMed
  107. J Cardiovasc Risk. 1996 Apr;3(2):213-9 - PubMed
  108. J Lipid Res. 1998 Jul;39(7):1412-20 - PubMed
  109. J Lipid Res. 2020 Sep;61(9):1253 - PubMed
  110. J Lipid Res. 2015 Jul;56(7):1308-17 - PubMed
  111. Science. 1987 Oct 16;238(4825):363-6 - PubMed
  112. BMC Med Genet. 2011 Jun 29;12:89 - PubMed
  113. J Vasc Res. 2007;44(1):61-6 - PubMed
  114. J Lipid Res. 1970 Nov;11(6):565-70 - PubMed
  115. Prog Mol Biol Transl Sci. 2010;93:213-33 - PubMed
  116. Biochim Biophys Acta. 2012 Oct;1821(10):1370-8 - PubMed
  117. N Engl J Med. 2017 Apr 27;376(17):1647-1658 - PubMed
  118. Biochim Biophys Acta. 1990 Feb 6;1042(2):188-92 - PubMed
  119. Open Biol. 2016 Apr;6(4):150272 - PubMed
  120. J Biol Chem. 1975 Jan 10;250(1):182-90 - PubMed
  121. Comp Biochem Physiol B. 1989;94(1):19-25 - PubMed
  122. Circulation. 2019 Aug 6;140(6):470-486 - PubMed
  123. Arterioscler Thromb Vasc Biol. 2002 Sep 1;22(9):1470-4 - PubMed
  124. J Biol Chem. 1995 Oct 27;270(43):25396-401 - PubMed
  125. J Clin Endocrinol Metab. 2011 Oct;96(10):E1675-9 - PubMed
  126. Mol Metab. 2017 Oct;6(10):1137-1149 - PubMed
  127. Biochemistry. 1973 Apr 24;12(9):1828-33 - PubMed
  128. Proc Natl Acad Sci U S A. 2021 Mar 23;118(12): - PubMed
  129. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8342-6 - PubMed
  130. Cell Metab. 2007 Apr;5(4):279-91 - PubMed
  131. J Biol Chem. 2009 May 8;284(19):13213-22 - PubMed
  132. Elife. 2016 Jan 03;5:e12095 - PubMed
  133. Arterioscler Thromb. 1993 Feb;13(2):190-6 - PubMed
  134. Am J Pathol. 1983 Dec;113(3):341-58 - PubMed
  135. Curr Opin Lipidol. 2012 Aug;23(4):310-20 - PubMed
  136. J Biol Chem. 1986 Oct 5;261(28):12918-21 - PubMed
  137. J Biol Chem. 1993 Jul 5;268(19):14168-75 - PubMed
  138. CMAJ. 2007 Apr 10;176(8):1113-20 - PubMed
  139. Circulation. 1998 Aug 11;98(6):519-27 - PubMed
  140. J Biol Chem. 2002 Feb 8;277(6):4334-42 - PubMed
  141. Arterioscler Thromb Vasc Biol. 2017 Jun;37(6):1206-1212 - PubMed
  142. Arterioscler Thromb Vasc Biol. 2013 Mar;33(3):474-80 - PubMed
  143. J Intern Med. 2012 Aug;272(2):185-96 - PubMed
  144. J Lipid Res. 2021 Mar 21;62:100068 - PubMed
  145. J Biol Chem. 2005 Jul 8;280(27):25383-7 - PubMed
  146. J Lipid Res. 2005 Feb;46(2):297-306 - PubMed
  147. PLoS One. 2014 May 23;9(5):e98368 - PubMed
  148. Diabetes Care. 2019 Dec;42(12):2307-2314 - PubMed
  149. Curr Opin Lipidol. 2016 Oct;27(5):473-83 - PubMed
  150. Atherosclerosis. 2021 Mar;320:10-18 - PubMed
  151. Int J Mol Sci. 2019 Nov 26;20(23): - PubMed
  152. Biochemistry. 1995 Jun 6;34(22):7401-8 - PubMed
  153. J Biol Chem. 2003 Oct 24;278(43):41804-9 - PubMed
  154. Endocrinology. 2005 Nov;146(11):4943-50 - PubMed
  155. PLoS One. 2015 Mar 26;10(3):e0123088 - PubMed
  156. J Lipid Res. 2013 Apr;54(4):1124-34 - PubMed
  157. Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17450-5 - PubMed
  158. Clin Genet. 1999 Jun;55(6):450-4 - PubMed
  159. J Biol Chem. 1990 Dec 25;265(36):22453-9 - PubMed
  160. Clin Chim Acta. 2018 Mar;478:200-215 - PubMed
  161. Mol Metab. 2020 Oct;40:101033 - PubMed
  162. Ann N Y Acad Sci. 1997 Apr 15;811:311-22; 322-4 - PubMed
  163. Clin Chem. 2005 Feb;51(2):351-9 - PubMed
  164. Drugs. 2019 Aug;79(12):1349-1354 - PubMed
  165. Curr Atheroscler Rep. 2019 May 20;21(8):27 - PubMed
  166. N Engl J Med. 2014 Jul 3;371(1):32-41 - PubMed
  167. Scand J Clin Lab Invest Suppl. 1978;150:53-8 - PubMed
  168. Biochem Biophys Res Commun. 2000 Apr 29;271(1):15-21 - PubMed
  169. Cell Metab. 2010 Jul 7;12(1):42-52 - PubMed
  170. J Biol Chem. 1988 May 25;263(15):7277-86 - PubMed
  171. J Am Coll Cardiol. 2005 Apr 5;45(7):1013-7 - PubMed
  172. Cell Metab. 2010 Dec 1;12(6):580-92 - PubMed
  173. Circ Res. 2007 Oct 12;101(8):777-83 - PubMed
  174. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2748-53 - PubMed
  175. J Lipid Res. 2011 Aug;52(8):1575-82 - PubMed
  176. J Biol Chem. 2000 Feb 25;275(8):5694-701 - PubMed
  177. Biochem Biophys Res Commun. 1972 Jan 31;46(2):375-82 - PubMed
  178. Biochim Biophys Acta. 1977 Jun 22;487(3):472-86 - PubMed
  179. J Biol Chem. 2015 May 8;290(19):11865-77 - PubMed
  180. Biochemistry. 1985 Sep 24;24(20):5606-11 - PubMed
  181. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9252-6 - PubMed
  182. Proc Natl Acad Sci U S A. 2020 Feb 25;117(8):4337-4346 - PubMed
  183. Mol Metab. 2017 Jun 19;6(8):809-818 - PubMed
  184. N Engl J Med. 2010 Dec 2;363(23):2220-7 - PubMed
  185. J Atheroscler Thromb. 1994;1(2):98-102 - PubMed
  186. Biochem Biophys Res Commun. 2008 Dec 26;377(4):1294-8 - PubMed
  187. Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):366-72 - PubMed
  188. J Lipid Res. 1993 Sep;34(9):1555-64 - PubMed
  189. J Biol Chem. 1991 Sep 25;266(27):18259-67 - PubMed
  190. Nat Genet. 2002 Feb;30(2):151-7 - PubMed
  191. Biochim Biophys Acta. 1979 Jun 21;573(3):501-9 - PubMed
  192. Cell Metab. 2018 May 01;27(5):1055-1066.e3 - PubMed
  193. Endocrinology. 2017 May 1;158(5):1252-1259 - PubMed
  194. J Clin Invest. 1973 Jul;52(7):1578-85 - PubMed
  195. J Lipid Res. 2005 Jul;46(7):1484-90 - PubMed
  196. J Lipid Res. 1999 Oct;40(10):1875-82 - PubMed
  197. Am J Cardiol. 2004 Sep 15;94(6):720-4 - PubMed
  198. JCI Insight. 2020 Sep 3;5(17): - PubMed
  199. J Lipid Res. 2001 Aug;42(8):1180-6 - PubMed
  200. Biochemistry. 2003 Feb 25;42(7):1872-89 - PubMed
  201. Ann Intern Med. 2020 Nov 3;173(9):764-765 - PubMed
  202. J Biol Chem. 1970 Dec 25;245(24):6588-94 - PubMed
  203. J Biol Chem. 2015 Jul 17;290(29):18029-18044 - PubMed
  204. J Biol Chem. 2014 Jul 11;289(28):19491-9 - PubMed
  205. J Biol Chem. 2000 Dec 1;275(48):37504-9 - PubMed
  206. N Engl J Med. 2019 Aug 8;381(6):531-542 - PubMed
  207. J Biol Chem. 1999 Dec 3;274(49):34629-36 - PubMed
  208. J Biol Chem. 2002 Aug 30;277(35):31900-8 - PubMed
  209. J Clin Invest. 1994 Apr;93(4):1683-90 - PubMed
  210. J Lipid Res. 2009 Dec;50(12):2421-9 - PubMed
  211. J Clin Endocrinol Metab. 2009 Nov;94(11):4584-90 - PubMed
  212. J Clin Invest. 2013 Jun;123(6):2742-51 - PubMed
  213. J Clin Invest. 1992 Feb;89(2):373-80 - PubMed
  214. Elife. 2016 Dec 08;5: - PubMed
  215. J Biol Chem. 2001 Nov 30;276(48):44512-20 - PubMed
  216. Proc Natl Acad Sci U S A. 2019 May 21;116(21):10360-10365 - PubMed
  217. J Lipid Res. 1992 Aug;33(8):1165-70 - PubMed
  218. Curr Opin Lipidol. 2010 Jun;21(3):218-28 - PubMed
  219. J Lipid Res. 2020 Mar;61(3):365-375 - PubMed
  220. N Engl J Med. 2017 Jul 20;377(3):222-232 - PubMed
  221. J Lipid Res. 2017 May;58(5):840-852 - PubMed
  222. J Biol Chem. 1998 Nov 20;273(47):30979-84 - PubMed
  223. Clin Chim Acta. 2006 May;367(1-2):36-47 - PubMed
  224. Front Endocrinol (Lausanne). 2014 Jan 23;5:4 - PubMed
  225. J Lipid Res. 2010 Apr;51(4):824-31 - PubMed
  226. N Engl J Med. 2016 Mar 24;374(12):1123-33 - PubMed
  227. Nat Genet. 2016 Jun;48(6):634-9 - PubMed
  228. Sci Rep. 2018 Jul 12;8(1):10516 - PubMed
  229. Biochim Biophys Acta. 2015 Feb;1851(2):163-71 - PubMed
  230. J Biol Chem. 2004 Mar 12;279(11):10643-8 - PubMed
  231. J Biol Chem. 1955 Jul;215(1):15-26 - PubMed
  232. Cell Metab. 2014 May 6;19(5):849-60 - PubMed
  233. Physiol Rev. 2004 Oct;84(4):1381-478 - PubMed
  234. J Lipid Res. 1992 Feb;33(2):141-66 - PubMed
  235. Arterioscler Thromb Vasc Biol. 2013 Jul;33(7):1529-37 - PubMed

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