Distinct cholesterol and phospholipid incorporation at the platelet plasmamembrane of hyperlipidemic subjects: structural order and function

Plasma lipid composition, platelet aggregation, cholesterol (Ch)/glycoprote in IIb-IIIa (GP) and phospholipid (Ph)/GP molar ratios, fatty acid composit ion and structural order (1, 6-diphenyl-1, 3, 5-hexatriene (DPH) fluorescen ce anisotropy at 35 degrees C (r(DPH,35)) of human platelet plasma membrane s (HPPM) were measured in four groups of hyperlipidemic patients (II: plasm a Ch < 250 mg/dl and TG (triglycerides) <220 mg/dl, n = 21; III: Ch > 250 m g/dl and TG < 220 mg/dl, n = 23; IV: Ch < 250 mg/dl and TG > 220 mg/dl, n = 18; and V: Ch > 250 mg/dl and TG > 220 mg/dl, II = 12) and compared with t hose of the control group (I). Our results were: (i) in groups III, Iv and V the HPPM (Ch + Ph)/GP molar ratio increased 7.0 +/- 7.7 % (mean +/- SD); (ii) the Ph/GP molar ratio increased significantly in groups III, IV and V, but most in IV and V, while the Ch/GP molar ratio increased only in groups III and V; (iii) the mean relative increase of Ch with respect to Ph in th e HPPM of groups III, IV and V was 140% 21% and 54%, respectively; (iv) the Ch/GP molar ratio was correlated with LDL-Ch (0.41 +/- 0.16, P < 0.002, It = 55, for all the subjects and 0.60 +/- 0.11, P < 2.10(-4), n = 33, for su bjects with TG > 220 mg/dl), however, it was totally uncorrelated with HDL- Ch; (v) the HPPM Ch/Ph molar ratio was positively correlated with plasma Ch (r = 0.51 +/- 0.08, P < 1.10(-6), n = 83) and with (LDL + HDL) Ch (r = 0.6 4 +/- 0.07, P < 1.10(-6), n = 73), the former correlation increased signifi cantly (r = 0.67 +/- 0.07, P < 1.10(-6), n = 53) when done only for subject s with TG < 220 mg/dl; (vi) the Ch/Ph molar ratio was only increased in gro up III (0.70 +/- 0.03, P < 3.10(-5) n = 23) and decreased in group IV (0.62 +/- 0.02, P < 0.001, n = 18); (vii) the fatty acid/GP molar ratio was sign ificantly increased in groups IV and V, however, a significant absolute and relative increase of C16:0 and C18:1 was observed only in severe hypertrig lyceridemia (> 500 mg/dl), together with a relative decrease of C18:0 and C 20:4 (n - 6); (viii) the HPPM structural order, as probed by r(DPH,35), was negatively correlated with plasma TG (r = - 0.61 +/- 0.10, P < 4.10(-5), n = 39), the Ph/GP molar ratio (r = -0.58 +/- 0.10, P < 2.10(-4), n = 39) an d the the (C18:1 + C18:2))/GP molar ratio (r = - 0.80 +/- 0.05, P < 1.10(-6 ), it = 39), however, it was independent of plasma and HPPM Ch; (ix) the hi gher HPPM Ch/Ph molar ratio in group III was associated (r = 0.58 +/- 0.12, P < 0.005, it = 22) with a moderately higher platelet reactivity to collag en. We conclude that Ch and Ph were distinctly incorporated to HPPM in the different groups of hyperlipidemia and, therefore, that the absolute increa se of Ch and Ph was more informative to understand the structural and funct ional modifications of the HPPM in hyperlipidemias, than the Ch/Ph molar ra tio. On the other hand, the r(DPH,35) was sensitive to the increase in the content of HPPM Ph and C18:1 + C18:2 and it was insensitive to the increase in the Ch content.