ATHERQSCLEROSIS UPDATE ATHEROSCLEROSE: LE POINT Canadian Atherosclerosis Society/Societe canadienne d'atherosclerose
Lipoprotein lipase Philip W. Connelly, PhD L ipoprotein lipase (LPL) is the primary enzyme involved in lipolysis of the plasma triglycerides (TG) of chylomicrons and verylow-density lipoproteins (VLDL). It is activated by plasma apolipoprotein C-II (apo C-1I). Deficiency of LPL or apo C-II results in hyperchylomicro-
nemia.' 2
nary bypass graft recipients treated for 2 years with agents that lowered the VLDL and LDL levels and elevated the HDL level.5'6 The distribution of apo C-III may be a marker of the balance between VLDL and HDL that reflects the "efficiency" of the LPL/apo C-II system. These provocative new observations will certainly prompt re-evaluation of the relation between plasma TG and HDL as predictors of atherosclerotic disease risk. They are consistent with the hypothesis that the LPL/apo C-Il system plays a central role in the metabolism of atherogenic and antiatherogenic lipoproteins. An understanding of this system is valuable in the prevention and reversal of athero-
LPL hydrolysis of plasma lipoprotein TG releases fatty acids to be used by tissues. LPL activity is regulated through hormone action by fasting, feeding, diet and exercise. The functional pool of LPL is bound at the luminal surface of endothelial cells by ionic interaction with a glycosaminoglycan. The major sites of functional LPL are the capillary endothelium of adipose tissue, heart muscle, skeletal sclerosis. muscle and lactating mammary gland. The enzyme is also found in lung, brain and kidney. References Newly secreted chylomicrons and VLDL acquire apolipoproteins, including apo C-II and apo C-III, 1. Brunzell JD, Austin MA: Plasma triglyceride levels and corofrom high-density lipoproteins (HDL). When chylonary disease. N Engi J Med 1989; 320: 1273-1274 micron TG or VLDL TG is hydrolyzed by LPL the WC, Little JA, Steiner G et al: Hypertriapo C-IT and apo C-III, as well as apo C-I, apo E, 2. Breckenridge associated with deficiency of apolipoprotein C-II. glyceridemia phospholipid and cholesterol, are transferred to N Engl J Med 1978; 298: 1265-1273 HDL.3 Thus, the LPL/apo C-II system is important in the reciprocal relationship between VLDL and 3. Alaupovic P: David Rubinstein Memorial Lecture: The biochemical and clinical significance of the interrelationship HDL. When LPL activity is high the VLDL concenbetween very low density and high density lipoproteins. Can J tration is typically low and the HDL concentration Biochem 1981; 59: 565-579 high, and vice versa.4 The plasma VLDL level represents the balance between hepatic production of 4. Kuusi T, Ehnholm C, Viikari J et al: Postheparin plasma lipoprotein and hepatic lipase are determinants of hypo- and VLDL and catabolism of VLDL by the LPL/apo C-II hyperalphalipoproteinemia. J Lipid Res 1989; 30: 1117-1126 system. Partial deficiencies of LPL may be a frequent cause of hypertriglyceridemias, including hy- 5. Blankenhorn DH, Alaupovic P, Wickham MS et al: Prediction of angiographic change in native human coronary arteries and perprebetalipoproteinemia alone or combined with aortocoronary bypass grafts: lipid and nonlipid risk factors. hyperbetalipoproteinemia. I Circulation 1990; 81: 470-476 The amount of apo C-III in HDL was recently found to be the most significant predictor of regres- 6. Havel RJ: Role of triglyceride-rich lipoproteins in progression of atherosclerosis. Ibid: 694-696 sion of coronary artery disease in a group of coroDr. Connelly is director of the Core Laboratory, Lipid Research Clinic, St. Michael's Hospital, Toronto.
The opinions expressed in this article are those of the author and not necessarily those of the Canadian Atherosclerosis Society. Reprint requests to: Dr. Philip W. Connelly, Rm. 102 WA, St. Michael's Hospital, 38 Shuter St., Toronto, Ont. M5B IA6 -
For prescribing information see page 327
CAN MED ASSOC J 1990; 143 (4)
295
Lipoprotein lipase Philip W. Connelly, PhD L ipoprotein lipase (LPL) is the primary enzyme involved in lipolysis of the plasma triglycerides (TG) of chylomicrons and verylow-density lipoproteins (VLDL). It is activated by plasma apolipoprotein C-II (apo C-1I). Deficiency of LPL or apo C-II results in hyperchylomicro-
nemia.' 2
nary bypass graft recipients treated for 2 years with agents that lowered the VLDL and LDL levels and elevated the HDL level.5'6 The distribution of apo C-III may be a marker of the balance between VLDL and HDL that reflects the "efficiency" of the LPL/apo C-II system. These provocative new observations will certainly prompt re-evaluation of the relation between plasma TG and HDL as predictors of atherosclerotic disease risk. They are consistent with the hypothesis that the LPL/apo C-Il system plays a central role in the metabolism of atherogenic and antiatherogenic lipoproteins. An understanding of this system is valuable in the prevention and reversal of athero-
LPL hydrolysis of plasma lipoprotein TG releases fatty acids to be used by tissues. LPL activity is regulated through hormone action by fasting, feeding, diet and exercise. The functional pool of LPL is bound at the luminal surface of endothelial cells by ionic interaction with a glycosaminoglycan. The major sites of functional LPL are the capillary endothelium of adipose tissue, heart muscle, skeletal sclerosis. muscle and lactating mammary gland. The enzyme is also found in lung, brain and kidney. References Newly secreted chylomicrons and VLDL acquire apolipoproteins, including apo C-II and apo C-III, 1. Brunzell JD, Austin MA: Plasma triglyceride levels and corofrom high-density lipoproteins (HDL). When chylonary disease. N Engi J Med 1989; 320: 1273-1274 micron TG or VLDL TG is hydrolyzed by LPL the WC, Little JA, Steiner G et al: Hypertriapo C-IT and apo C-III, as well as apo C-I, apo E, 2. Breckenridge associated with deficiency of apolipoprotein C-II. glyceridemia phospholipid and cholesterol, are transferred to N Engl J Med 1978; 298: 1265-1273 HDL.3 Thus, the LPL/apo C-II system is important in the reciprocal relationship between VLDL and 3. Alaupovic P: David Rubinstein Memorial Lecture: The biochemical and clinical significance of the interrelationship HDL. When LPL activity is high the VLDL concenbetween very low density and high density lipoproteins. Can J tration is typically low and the HDL concentration Biochem 1981; 59: 565-579 high, and vice versa.4 The plasma VLDL level represents the balance between hepatic production of 4. Kuusi T, Ehnholm C, Viikari J et al: Postheparin plasma lipoprotein and hepatic lipase are determinants of hypo- and VLDL and catabolism of VLDL by the LPL/apo C-II hyperalphalipoproteinemia. J Lipid Res 1989; 30: 1117-1126 system. Partial deficiencies of LPL may be a frequent cause of hypertriglyceridemias, including hy- 5. Blankenhorn DH, Alaupovic P, Wickham MS et al: Prediction of angiographic change in native human coronary arteries and perprebetalipoproteinemia alone or combined with aortocoronary bypass grafts: lipid and nonlipid risk factors. hyperbetalipoproteinemia. I Circulation 1990; 81: 470-476 The amount of apo C-III in HDL was recently found to be the most significant predictor of regres- 6. Havel RJ: Role of triglyceride-rich lipoproteins in progression of atherosclerosis. Ibid: 694-696 sion of coronary artery disease in a group of coroDr. Connelly is director of the Core Laboratory, Lipid Research Clinic, St. Michael's Hospital, Toronto.
The opinions expressed in this article are those of the author and not necessarily those of the Canadian Atherosclerosis Society. Reprint requests to: Dr. Philip W. Connelly, Rm. 102 WA, St. Michael's Hospital, 38 Shuter St., Toronto, Ont. M5B IA6 -
For prescribing information see page 327
CAN MED ASSOC J 1990; 143 (4)
295
