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Activation of lipoprotein lipase by blood platelets
Life Sciences Vol . 15, pp . 103-110 Printed in the U.S .A .
Pergamon Preae
ACTIVATION OF LIPOPROTEIIf LIPASB BT BLOOD PIATELETS Beung-Y11 Song, Arleae B . Oarfinkel and Michael C. Schotz Medical Service and Research, Veterans Administration Wadewrth Hospital Center, Los Angeles, Calif. 90073 and Dept . of Medicine, UCIA Bchool of Medicine, Los Angeles, Calif . 90024 (Received in final form 4 June 1974) Summery When an homogenate of human blood platelets is added to preparations of partially purified adipose tissue lipoprotein lipase, the lipase activity is markedly enhanced . The degree of activation is related to the amount of platelet hanogenate in the reaction mixture . The lipoprotein lipase activator in platelets is heat labile, nondielyzable, partially resistant to pepsin, and present mostly in the particulate fraction of platelet hamogenatee . Hydrolysis of plasma neutral lipid by the enzyme lipoprotein lipase ie an obligatory step in the deposition of triglyceride fatty acid in adipose tissue (1) .
A lipoprotein lipase modifier, heparin, has been used exten
sively as a tool in studying lipoprotein metabolism (2) .
In this regard it
is interesting that a part of the lipolytic activity of pre and post heparin blood has been reported to be associated with the platelets (3-5) " Several investigators have reported that lipoprotein lipase activity in post heparin plasma is inhibited by addition of platelet preparations (6-B) . In the current study we have reinvestigated the effect of platelets on lipo protein lipase activity using a partially purified adipose tissue preparation of the enzyme .
In contrast to the inhibition noted with post heparin plasma
our results show that platelets contain a factor which enhances adipose lipoprotein lipase activity .
103
104
Vol . 15, No . 1
Lipoprotein Lipase - Plat®lets
Materiale and Methode Preparation of platelets:
gach preparation required the platelets con-
centrated from 2 pints of human blood (type 0, Rh+ ) obtained from a commercial blood bank . 4' .
These conceatretee were centrilYiged at 100 xg for 10 min at
The sediments were washed in 0.9~ PaCl solvtion containing 1mM EATA and
centrifuged again at 2400 xg for 15 min at 4' .
The washed pellets Were re-
evspended in 0.05~I HH40H-NS4C1 buffer, pH8.6, containing 5'd sucrose, to give 2 to 4 x 109 platelets per ml . no red blood cells .
There were 105 white blood cells per ml but
The platelets were rapi8ly frozen in dry ice and thawed
at 3T two times and then homogenized at 4' with a Ten Hroeck glens tissue grinder.
The homogenates obtained were centrifY~ged at 2400 xg for 15 min,
and the homogenization and centrifugation steps repeated with the sediments . Hoth the supernatant fractions from the first hamogenizntlon and the rehamogenized aedimenta were combined and are referred to 1a this report ea platelet homogenate .
The time from venapuneture of the blood donor to enzyme assay
wne less than four hours .
For the localization study the platelet homog-
mates already treated as described above were centrifuged at 23,000 xg for 60 min and the pellet obtained suspended in 1~1~OH-AHlEC1 buffer. Lipoprotein lipase activity extracted from rat epididymal adipose tissue acetone powder vas fractionated by gel chromatography (9) . LPLa and LPI,b, were utilized in these studied .
Two fractions,
For measurement of lipopro
tein lipase activation partlaLty purified lipoprotein lipase fractions were mixed with platelet homogenate in a total volume of 0.4 ml and incubated for 5 min at 3'j' .
The combined platelet lipoprotein lipase mixtures were then
assayed for lipase activity by addition of 0.6 ml emulsified H3-triolein substrate mixture (10) .
Following a 60 min incubation at 3T the reaction was
terminated by adding 1 ml ](Y,1+ TCA.
The radioactive glycerol product was
assayed in s liquid scintillation counter (10) . described by Lowry, et al . (11) .
Protein was determined as
Vol.
15, No . 1
Lipoprotein Lipase - Platelets
10 5
Figure 1 ahovs the activation of tvo partially purified fractions of LPL by varying amounts of platelet homogenate .
Aliquots of LPLa and LPhb,
containing the same amount of protein, shoved relatively higher activity in the LPIs fraction .
The activity of both enayme fractions, LPLa and LPLh ,
markedly increased and reached a plateau after addition of a rather small amount of the platelet homogenate . observed .
A maximal 5 to 7 fold activation vas
The platelet homogenates appear to have a small amount of lipopro-
tein lipase activity relative to that present in adipose extracts after activation .
The lipoprotein lipase activity assayed is the presence of
platelet homogenate ie linear for at least 90 min (Fig . 2) . Figure 1 Effect of varying amounts of platelet protein on LPL activity .
IsO.; LPl9 ypLA7ELET a
a -
a 120
IPLbtPLATELET
~i
_________-__
one
alo
ml PLATELET
als
NOMOßENATE
~q__ ôso
Platelet homogenate (~} was reincubated with 0.18mg of partially purified LPIs (R) or LPLb (0~ for 5 min at 3~' in a total volume of 0.4 ml . Then the assay reaction vas started by addition of 0 .6m1 substrate mixture and the incubation continued for 60 min as described in the text . 0.9n1 platelet homogenate corneponds to 5.2mg protein. Lipoprotein lipase activity ie expressed in n moles glycerol per ml assay reaction mixture . These data are the mean of five determinations with the values of maximum activation varying from three to six times those of LPIg, and LPLb alone .
106
Vol . 15, No .
Lipoprotein Lipase - Platelets
Figure 2 Linearity of platelet-enhanced lipoprotein lipase activity with assay incubation time .
3 mg platelet homogenate (~) and 0 .07mg partially purified LPLb
(p) were assayed separately, and after combination and preincubation (0) for 5 min at 37 ° , in a total volume of 0 .4 ml . 0 .6 ml substrate mixture was added and the assay incubation continued for the time periods shown on the abscissa . Lipoprotein lipase activity is exprossed in n moles glycerol per ml assay reaction mixture . The results are the mean value of two experiments . To study the properties of the activation process, the activity of LPL was measured after varying the duration of preincubation of platelet hanogehates with enzyme fractions prior to addition of substrate .
Preincubations
for 1 to 15 min made no difference in the extent of activation .
The 11po-
protein lipase activator in platelet homogenates was found to be heat-labile
1
Vol . 15, No . 1
10 7
Lipoprotein Lipase - Platelets
since treatment of platelet homogenates at 62° for 15 min abolished the activating property .
After platelet homogenates were dialyzed overnight
against 0.05M NH40R-NS4C1 buffer, pR8.6, at 4° no loss of activator activity was observed .
When the platelet homogenate was separated into fractions by
centrifugation at 23,000 xg, most of the lipoprotein lipase activating principle appeared to be associated with the pellet .
The data for the relative
activation of LPLa by these centrifuged fractions are shown in Table I . Activation of the LPLb enzyme by the platelet fractions followed a similar pattern.
It is entirely possible that the small activation seen on addition
of the supernatant fraction (Table I) was due to psrticulates not separated by centrifugation .
When incubated with pepsin according to the method of
vanEyk (12), the activating principle in the platelet homogenate was only partially decreased (Table II), ie . slightly less than a 5096 decrease when assayed for activation of LPLa extracts . I TABLE Localization of LPL Activator in Platelet $omogenate .
PLATELEP FRACTION
HautocENATE suPSRNAT~ PRECIPITAT$
PROTEIN (mg)
65 20 45
LIPOPROTEIF LIPASE SPECIFIC TOTAL ACTIVITYC ACTIVITY (n moles (n moles glycerol glycerol) mg platelet prot .~hr) 29 .1 12 .9 35 " 3
1892 258 1588
PERCENT OF TOTAL ACTIVITY
loo 13 83
Platelet concentrates were homogenized as described in the text and centrifuged at 23,000 xg for 60 min at 4° to obtain fractions. Aliquots of the hamogermte and the fractions were preincubated for 5 min at 37° with 0 .18 mg partially purified LPLa is a total volume of 0.4 .m1 . Then 0 .6 ml substrate mixture was added and lipolytic activity determined . The results have been adjusted for lipase activity in the partially purified LPIg and the platelet fractions. The results are the mean of two experiments .
Lipoprotein Lipase - Platelets
10 8
Vol . 15, No . 1
II TAHLE Effect of Pepsin on LPL Activator In Platelet Homogenates .
Lipoprotein Lipase Activity of Platelet Homogenate + LPIg (n males g>,ycerol~ml assay mixture~hr)
(-)
Papain
(+)
109.7
56 .9
(1 hr)
116.9
65 .5
(2 hr)
28 mg Na7.4 mg pepsin we~ incubated with 4.6 mg cyeteine for 5 min at 37° . One aliquot EDTA and 90 mg . platelet homogenate were added to the mixture . of this mixture was incubated at 37 ° for 1 hr and a second aliquot similarly incubated for 2 hr . Then the two sampLea were dialyzed overnight against water at 4° to inactivate the pepsin . 0 .18 mg of partially purified LPIg rrea added to aliquots of the platelet homogenates in a total volume of 0.~ ml and incubated for 5 min et 37° . 0.6 ml of substrate mixture was added and LPL activity determined ss described in the text . 3lmilar treatment of platelet homogenates with no added pepsin showed that dialysis alone did not affect These values are the the LPL activity enhancing property of the homogenates . mean of two determinations . From our study it is clear that a platelet factor activates partially purified lipoprotein lipase prepared from rat epididymal fat pads . sible activation of di-and monog>tiyceride lipase was not studied .
The posIn regard
to the nature of this activator in platelets one possibility is that the pepsin - resistant factor may be a mucopolyseccharide-protein complex. Olsson and Gardell (13) reported isolation of a sulfated mucopolysaccharide from blood platelets which behaved like chondroitin sulfate rather than heparin.
However, although nonsulfsted mucopolyeacchardiee in smaller
amounts have also been found in blood platelets (14), our data are not yet extensive enough to draw any definite conclusion .
The lipoprotein lipase
assay used in the present study employs dog serum, at a saturating concentration for the activation of the triglyceride substrate (10) .
If it ie
presumed that the npopolypeptide R-glu is present in dog serum and, as in human serum it is the principal activator of the lipoprotein lipase system
Vol . 15, No . 1
10 9
Lipoprotein Lipase - Platelets
(15-17) then it is obvious that the platelet factor is not identical to the apopolypeptide activator R-glu. It is likely that inhibition of LPL activity by platelets previously reported on the basis of optical density changes (6-B) vas due to problems inherent in the methodology employed since the platelets themselves and the ability of platelets to aggregate markedly affect these optical density measurements . Though platelet adhesiveness appears inversely correlated with plasma lipoprotein-lipase activity(18),the physiological significance of a lipoprotein lipase activator in platelets is not clear.
It is of interest that
this activation of lipoprotein lipase by platelets may play a major role in the formation of atheroma . Zilversmit (19) recently proposed that "atherogenesis may result from the liberation of cholesterol-rich fragments in proximity to the arterial endothelium when pre-beta-lipoproteins or chylomicrons are degraded by arterial lipoprotein lipase .
High local concentra-
boas of cholesterol-rich lipoproteins resulting from surface lipolysis and the release of potentially injurious fatty acids would enhance the uptake of cholesterol by the arterial intima ."
It is known that when the endothelial
cells are injured by a variety of means one of the first events following injury is the appearance of platelets at the site of injury .
If platelets
could release the factor which enhances lipoprotein lipase activity, Zilveremu 's hypothesis, cited above, might explain why atheroma occur at defined sites along the aorta. Acknowledgmen ts This work is supported by United States Public Health Service Grant No . 4706 from the National Institute of Arthritis and Metabolic Diseases, by a Grant-in-Aid from the American Heart Association and funds contributed by the Los Angeles County Heart Association .
110
Lipoprotein Lipase - Platelets
Vol. 15, No . 1
References 1.
Robinson, D.S ., Comprehensive Biochemistry 18 51 1970 .
2.
Robinson, D.S . and P,M. Harris, Quant. J. Exptl. Phyeiol. 44 80 1959 .
3.
Smith, J.C . and J.J . Barboriak, Am . J. Physiol. 212 n13 1967 .
4.
Engelberg, H., J. Atheroscler . Rea . 10 353 1969 .
5.
Bucher, H.~d., Helv . Med. Acta 37 47 1973 .
6.
Mitchell, J.R .A ., Lancet 1 169 1959 "
?
Gardikas, C ., D. Thamopoulous, G. Arapakie, and H. Nassi, Acta Haemat . (Hasel) 24 274 19F~ .
8.
Honett, C. and P,J. Nestel, Am . J. Physiol. 199 803 1960 .
9.
Garfinkel, A.S . and M,C. Schotz, J. Lipid Ree . 13 63 1972 .
10 .
Schotz, M.C . and A .S, Carfinkel, J. Lipid Res. 13 824 1972 .
11 .
Lowry, O.H ., N.J . Rosebrough, A,L. Farr, and R,J. Randall, J. Biol . Chem . 193 265 1951 .
12 .
VanEyk, H.G ., Biothun. Biophye. Acta 127 241 1966 .
13 .
Olsson, I. and S . Garden, Hiochim. Biophys. Acta, 141 348 1967 .
14 .
Odell, T.T ., Jr . and B. Anderson, Proc . Soc. Exptl. Biol . Med., 94 151 1957 .
15 .
IaRosa, J.C ., R,I. Levy, P. Herbert, S.E. Lux and D.S, Fredrickson, Biochem . Hiophys . Res . Comet. 41 57 1970 .
16 .
Hovel, R.J ., V.G, Shore, H. Shore and D.M . Bier, Circ . Ree. 27 595 1970 .
17 .
Brown, W.V . and M. L. Haginsky, Biochem. Hiophys. Res. Comet. 46 375 1972 .
18 .
Negus, D., D.J . Pinto, and W.W, Slack, Lancet 1 1202 1971 .
19 .
Zilversmit, D.B ., Circulation Ree . 33 633 1973 .
Pergamon Preae
ACTIVATION OF LIPOPROTEIIf LIPASB BT BLOOD PIATELETS Beung-Y11 Song, Arleae B . Oarfinkel and Michael C. Schotz Medical Service and Research, Veterans Administration Wadewrth Hospital Center, Los Angeles, Calif. 90073 and Dept . of Medicine, UCIA Bchool of Medicine, Los Angeles, Calif . 90024 (Received in final form 4 June 1974) Summery When an homogenate of human blood platelets is added to preparations of partially purified adipose tissue lipoprotein lipase, the lipase activity is markedly enhanced . The degree of activation is related to the amount of platelet hanogenate in the reaction mixture . The lipoprotein lipase activator in platelets is heat labile, nondielyzable, partially resistant to pepsin, and present mostly in the particulate fraction of platelet hamogenatee . Hydrolysis of plasma neutral lipid by the enzyme lipoprotein lipase ie an obligatory step in the deposition of triglyceride fatty acid in adipose tissue (1) .
A lipoprotein lipase modifier, heparin, has been used exten
sively as a tool in studying lipoprotein metabolism (2) .
In this regard it
is interesting that a part of the lipolytic activity of pre and post heparin blood has been reported to be associated with the platelets (3-5) " Several investigators have reported that lipoprotein lipase activity in post heparin plasma is inhibited by addition of platelet preparations (6-B) . In the current study we have reinvestigated the effect of platelets on lipo protein lipase activity using a partially purified adipose tissue preparation of the enzyme .
In contrast to the inhibition noted with post heparin plasma
our results show that platelets contain a factor which enhances adipose lipoprotein lipase activity .
103
104
Vol . 15, No . 1
Lipoprotein Lipase - Plat®lets
Materiale and Methode Preparation of platelets:
gach preparation required the platelets con-
centrated from 2 pints of human blood (type 0, Rh+ ) obtained from a commercial blood bank . 4' .
These conceatretee were centrilYiged at 100 xg for 10 min at
The sediments were washed in 0.9~ PaCl solvtion containing 1mM EATA and
centrifuged again at 2400 xg for 15 min at 4' .
The washed pellets Were re-
evspended in 0.05~I HH40H-NS4C1 buffer, pH8.6, containing 5'd sucrose, to give 2 to 4 x 109 platelets per ml . no red blood cells .
There were 105 white blood cells per ml but
The platelets were rapi8ly frozen in dry ice and thawed
at 3T two times and then homogenized at 4' with a Ten Hroeck glens tissue grinder.
The homogenates obtained were centrifY~ged at 2400 xg for 15 min,
and the homogenization and centrifugation steps repeated with the sediments . Hoth the supernatant fractions from the first hamogenizntlon and the rehamogenized aedimenta were combined and are referred to 1a this report ea platelet homogenate .
The time from venapuneture of the blood donor to enzyme assay
wne less than four hours .
For the localization study the platelet homog-
mates already treated as described above were centrifuged at 23,000 xg for 60 min and the pellet obtained suspended in 1~1~OH-AHlEC1 buffer. Lipoprotein lipase activity extracted from rat epididymal adipose tissue acetone powder vas fractionated by gel chromatography (9) . LPLa and LPI,b, were utilized in these studied .
Two fractions,
For measurement of lipopro
tein lipase activation partlaLty purified lipoprotein lipase fractions were mixed with platelet homogenate in a total volume of 0.4 ml and incubated for 5 min at 3'j' .
The combined platelet lipoprotein lipase mixtures were then
assayed for lipase activity by addition of 0.6 ml emulsified H3-triolein substrate mixture (10) .
Following a 60 min incubation at 3T the reaction was
terminated by adding 1 ml ](Y,1+ TCA.
The radioactive glycerol product was
assayed in s liquid scintillation counter (10) . described by Lowry, et al . (11) .
Protein was determined as
Vol.
15, No . 1
Lipoprotein Lipase - Platelets
10 5
Figure 1 ahovs the activation of tvo partially purified fractions of LPL by varying amounts of platelet homogenate .
Aliquots of LPLa and LPhb,
containing the same amount of protein, shoved relatively higher activity in the LPIs fraction .
The activity of both enayme fractions, LPLa and LPLh ,
markedly increased and reached a plateau after addition of a rather small amount of the platelet homogenate . observed .
A maximal 5 to 7 fold activation vas
The platelet homogenates appear to have a small amount of lipopro-
tein lipase activity relative to that present in adipose extracts after activation .
The lipoprotein lipase activity assayed is the presence of
platelet homogenate ie linear for at least 90 min (Fig . 2) . Figure 1 Effect of varying amounts of platelet protein on LPL activity .
IsO.; LPl9 ypLA7ELET a
a -
a 120
IPLbtPLATELET
~i
_________-__
one
alo
ml PLATELET
als
NOMOßENATE
~q__ ôso
Platelet homogenate (~} was reincubated with 0.18mg of partially purified LPIs (R) or LPLb (0~ for 5 min at 3~' in a total volume of 0.4 ml . Then the assay reaction vas started by addition of 0 .6m1 substrate mixture and the incubation continued for 60 min as described in the text . 0.9n1 platelet homogenate corneponds to 5.2mg protein. Lipoprotein lipase activity ie expressed in n moles glycerol per ml assay reaction mixture . These data are the mean of five determinations with the values of maximum activation varying from three to six times those of LPIg, and LPLb alone .
106
Vol . 15, No .
Lipoprotein Lipase - Platelets
Figure 2 Linearity of platelet-enhanced lipoprotein lipase activity with assay incubation time .
3 mg platelet homogenate (~) and 0 .07mg partially purified LPLb
(p) were assayed separately, and after combination and preincubation (0) for 5 min at 37 ° , in a total volume of 0 .4 ml . 0 .6 ml substrate mixture was added and the assay incubation continued for the time periods shown on the abscissa . Lipoprotein lipase activity is exprossed in n moles glycerol per ml assay reaction mixture . The results are the mean value of two experiments . To study the properties of the activation process, the activity of LPL was measured after varying the duration of preincubation of platelet hanogehates with enzyme fractions prior to addition of substrate .
Preincubations
for 1 to 15 min made no difference in the extent of activation .
The 11po-
protein lipase activator in platelet homogenates was found to be heat-labile
1
Vol . 15, No . 1
10 7
Lipoprotein Lipase - Platelets
since treatment of platelet homogenates at 62° for 15 min abolished the activating property .
After platelet homogenates were dialyzed overnight
against 0.05M NH40R-NS4C1 buffer, pR8.6, at 4° no loss of activator activity was observed .
When the platelet homogenate was separated into fractions by
centrifugation at 23,000 xg, most of the lipoprotein lipase activating principle appeared to be associated with the pellet .
The data for the relative
activation of LPLa by these centrifuged fractions are shown in Table I . Activation of the LPLb enzyme by the platelet fractions followed a similar pattern.
It is entirely possible that the small activation seen on addition
of the supernatant fraction (Table I) was due to psrticulates not separated by centrifugation .
When incubated with pepsin according to the method of
vanEyk (12), the activating principle in the platelet homogenate was only partially decreased (Table II), ie . slightly less than a 5096 decrease when assayed for activation of LPLa extracts . I TABLE Localization of LPL Activator in Platelet $omogenate .
PLATELEP FRACTION
HautocENATE suPSRNAT~ PRECIPITAT$
PROTEIN (mg)
65 20 45
LIPOPROTEIF LIPASE SPECIFIC TOTAL ACTIVITYC ACTIVITY (n moles (n moles glycerol glycerol) mg platelet prot .~hr) 29 .1 12 .9 35 " 3
1892 258 1588
PERCENT OF TOTAL ACTIVITY
loo 13 83
Platelet concentrates were homogenized as described in the text and centrifuged at 23,000 xg for 60 min at 4° to obtain fractions. Aliquots of the hamogermte and the fractions were preincubated for 5 min at 37° with 0 .18 mg partially purified LPLa is a total volume of 0.4 .m1 . Then 0 .6 ml substrate mixture was added and lipolytic activity determined . The results have been adjusted for lipase activity in the partially purified LPIg and the platelet fractions. The results are the mean of two experiments .
Lipoprotein Lipase - Platelets
10 8
Vol . 15, No . 1
II TAHLE Effect of Pepsin on LPL Activator In Platelet Homogenates .
Lipoprotein Lipase Activity of Platelet Homogenate + LPIg (n males g>,ycerol~ml assay mixture~hr)
(-)
Papain
(+)
109.7
56 .9
(1 hr)
116.9
65 .5
(2 hr)
28 mg Na7.4 mg pepsin we~ incubated with 4.6 mg cyeteine for 5 min at 37° . One aliquot EDTA and 90 mg . platelet homogenate were added to the mixture . of this mixture was incubated at 37 ° for 1 hr and a second aliquot similarly incubated for 2 hr . Then the two sampLea were dialyzed overnight against water at 4° to inactivate the pepsin . 0 .18 mg of partially purified LPIg rrea added to aliquots of the platelet homogenates in a total volume of 0.~ ml and incubated for 5 min et 37° . 0.6 ml of substrate mixture was added and LPL activity determined ss described in the text . 3lmilar treatment of platelet homogenates with no added pepsin showed that dialysis alone did not affect These values are the the LPL activity enhancing property of the homogenates . mean of two determinations . From our study it is clear that a platelet factor activates partially purified lipoprotein lipase prepared from rat epididymal fat pads . sible activation of di-and monog>tiyceride lipase was not studied .
The posIn regard
to the nature of this activator in platelets one possibility is that the pepsin - resistant factor may be a mucopolyseccharide-protein complex. Olsson and Gardell (13) reported isolation of a sulfated mucopolysaccharide from blood platelets which behaved like chondroitin sulfate rather than heparin.
However, although nonsulfsted mucopolyeacchardiee in smaller
amounts have also been found in blood platelets (14), our data are not yet extensive enough to draw any definite conclusion .
The lipoprotein lipase
assay used in the present study employs dog serum, at a saturating concentration for the activation of the triglyceride substrate (10) .
If it ie
presumed that the npopolypeptide R-glu is present in dog serum and, as in human serum it is the principal activator of the lipoprotein lipase system
Vol . 15, No . 1
10 9
Lipoprotein Lipase - Platelets
(15-17) then it is obvious that the platelet factor is not identical to the apopolypeptide activator R-glu. It is likely that inhibition of LPL activity by platelets previously reported on the basis of optical density changes (6-B) vas due to problems inherent in the methodology employed since the platelets themselves and the ability of platelets to aggregate markedly affect these optical density measurements . Though platelet adhesiveness appears inversely correlated with plasma lipoprotein-lipase activity(18),the physiological significance of a lipoprotein lipase activator in platelets is not clear.
It is of interest that
this activation of lipoprotein lipase by platelets may play a major role in the formation of atheroma . Zilversmit (19) recently proposed that "atherogenesis may result from the liberation of cholesterol-rich fragments in proximity to the arterial endothelium when pre-beta-lipoproteins or chylomicrons are degraded by arterial lipoprotein lipase .
High local concentra-
boas of cholesterol-rich lipoproteins resulting from surface lipolysis and the release of potentially injurious fatty acids would enhance the uptake of cholesterol by the arterial intima ."
It is known that when the endothelial
cells are injured by a variety of means one of the first events following injury is the appearance of platelets at the site of injury .
If platelets
could release the factor which enhances lipoprotein lipase activity, Zilveremu 's hypothesis, cited above, might explain why atheroma occur at defined sites along the aorta. Acknowledgmen ts This work is supported by United States Public Health Service Grant No . 4706 from the National Institute of Arthritis and Metabolic Diseases, by a Grant-in-Aid from the American Heart Association and funds contributed by the Los Angeles County Heart Association .
110
Lipoprotein Lipase - Platelets
Vol. 15, No . 1
References 1.
Robinson, D.S ., Comprehensive Biochemistry 18 51 1970 .
2.
Robinson, D.S . and P,M. Harris, Quant. J. Exptl. Phyeiol. 44 80 1959 .
3.
Smith, J.C . and J.J . Barboriak, Am . J. Physiol. 212 n13 1967 .
4.
Engelberg, H., J. Atheroscler . Rea . 10 353 1969 .
5.
Bucher, H.~d., Helv . Med. Acta 37 47 1973 .
6.
Mitchell, J.R .A ., Lancet 1 169 1959 "
?
Gardikas, C ., D. Thamopoulous, G. Arapakie, and H. Nassi, Acta Haemat . (Hasel) 24 274 19F~ .
8.
Honett, C. and P,J. Nestel, Am . J. Physiol. 199 803 1960 .
9.
Garfinkel, A.S . and M,C. Schotz, J. Lipid Ree . 13 63 1972 .
10 .
Schotz, M.C . and A .S, Carfinkel, J. Lipid Res. 13 824 1972 .
11 .
Lowry, O.H ., N.J . Rosebrough, A,L. Farr, and R,J. Randall, J. Biol . Chem . 193 265 1951 .
12 .
VanEyk, H.G ., Biothun. Biophye. Acta 127 241 1966 .
13 .
Olsson, I. and S . Garden, Hiochim. Biophys. Acta, 141 348 1967 .
14 .
Odell, T.T ., Jr . and B. Anderson, Proc . Soc. Exptl. Biol . Med., 94 151 1957 .
15 .
IaRosa, J.C ., R,I. Levy, P. Herbert, S.E. Lux and D.S, Fredrickson, Biochem . Hiophys . Res . Comet. 41 57 1970 .
16 .
Hovel, R.J ., V.G, Shore, H. Shore and D.M . Bier, Circ . Ree. 27 595 1970 .
17 .
Brown, W.V . and M. L. Haginsky, Biochem. Hiophys. Res. Comet. 46 375 1972 .
18 .
Negus, D., D.J . Pinto, and W.W, Slack, Lancet 1 1202 1971 .
19 .
Zilversmit, D.B ., Circulation Ree . 33 633 1973 .