Platelets in patients with homozygous familial hypercholesterolemia are sensitive to Ca(2+)-mobilizing activity of low density lipoproteins.
While some data suggest that Ca(2+)-mobilizing effects of low density lipoprotein (LDL) in platelets are mediated by a specific membrane receptor, the data about the nature of this lipoprotein-binding site are contradictory. This work was performed in order to assess possible involvement of apolipoprotein (apo) B,E receptor, present in most cell types. To answer the question we compared effects of LDL in normal platelets and those obtained from patients with homozygous familial hypercholesterolemia (HFH), characterized by absence of functional apo B,E receptors. We have found that in accordance with previous results LDL induced instant reversible elevation of free cytoplasmic calcium concentration ([Ca2+]i) in fura-2-loaded platelets. The effect was observed both in healthy and HFH groups. Neither half-maximal effective concentrations nor maximal effects of LDL differed significantly between two groups. Ca(2+)-mobilizing effects of lipoproteins were potentiated about 4-fold by epinephrine and completely blocked by prostaglandin E1 both in platelets of healthy and HFH subjects. The similarity of lipoprotein effects in control and HFH platelets is evidence that apo B,E receptor does not mediate the Ca(2+)-mobilizing activity of LDL in this cell type.
Bochkov
V N
VN
Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia.
Matchin
Y G
YG
Fuki
I V
IV
Lyakishev
A A
AA
Tkachuk
V A
VA
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D002648:Child; D003593:Cytoplasm / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000235:genetics; D008077:Lipoproteins, LDL / Q000502:physiology*; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D018110:Receptors, Lipoprotein
D008077:Lipoproteins, LDL; D010972:Platelet Activating Factor; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; C032531:apolipoprotein B,E receptor; D000244:Adenosine Diphosphate; D000527:Alprostadil; D002118:Calcium; D004837:Epinephrine