Lipolysis of triglyceride-rich lipoproteins activates coagulant factor XII: a study in familial lipoprotein-lipase deficiency.
A high factor VII coagulant activity (VIIc), a marker of increased risk of coronary heart disease, is frequently found in types IIb and IV hyperlipidaemia, but its cause is not fully understood. Factor VII can be activated by factor XIIa, generated from factor XII upon activation of the contact system of coagulation. Ten patients with familial lipoprotein-lipase (LPL) deficiency and 10 healthy control subjects were therefore compared to explore the hypothesis that high concentrations of unesterified fatty acids (UFA), released from triglyceride-rich lipoproteins by LPL, are a source of factor XII activation and hence the increased VIIc that is observed post-prandially and in non-LPL-deficient hypertriglyceridaemic states. Mean plasma cholesterol and triglyceride concentrations were, respectively, 1.5- and 19-fold higher in the patients than controls, due to increases in very-low-density lipoproteins and chylomicrons. The concentration and composition of plasma UFA were similar in both groups. In conformity with the hypothesis, VIIc was not increased in the LPL-deficient group, despite their massive hypertriglyceridaemia. Furthermore, when the patients' plasma was treated with LPL, factor XII was activated promptly and substantially, whereas no similar effect was observed in the controls. These results suggest that high concentrations of circulating triglyceride-rich lipoproteins will increase VIIc in the presence of LPL.
Mitropoulos
K A
KA
MRC Epidemiology Medical Care Unit, Wolfson Institute of Preventive Medicine, St Bartholomew's Medical College, London, UK.
Miller
G J
GJ
Watts
G F
GF
Durrington
P N
PN
D000328:Adult; D005167:Factor VII / Q000378:metabolism; D005174:Factor XII / Q000378:metabolism / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000145:classification; D005260:Female; D006801:Humans; D008066:Lipolysis; D008071:Lipoprotein Lipase / Q000172:deficiency*; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D008074:Lipoproteins; D014280:Triglycerides; D005167:Factor VII; D005174:Factor XII; D008071:Lipoprotein Lipase