Plasma Lipids and Platelet Membrane Fluidity in Essential Hypertension

Summary

Essential hypertension is often associated with high levels of plasma cholesterol or triglycerides. The relationships between plasma lipids and platelet lipids, membrane fluidity and functions in untreated hypertensive patients were investigated by measuring the fluorescence anisotropies of two fluorescent dyes (DPH and its cationic derivative, TMA-DPH, with different subcellular localization), cytosolic Ca²⁺ and pH, cyclic AMP content and aggregation to ADP and collagen. Hypercholesterolemia was found to be accompanied by a rise in platelet cholesterol content without changes in TMA-DPH or DPH anisotropies whereas hypertriglyceridemia was associated with a decreased cholesterol to phospholipid molar ratio, a decreased DPH anisotropy and a tendency of the cytosol to alkalinize. These results point out the differences between the effects of an acute cholesterol load and those of chronic hypercholesterolemia on platelet membrane microviscosity and aggregation. They demonstrate a strong association between plasma triglyceride levels and platelet membrane structure.

• References

• 1 Chobanian AV. Single risk factor intervention may be inadequate to inhibit atherosclerosis progression when hypertension and hypercholesterolemia coexist. Hypertension 1991; 18: 130-131
• 2 Cambien F, Jacqueson A, Richard JL, Warnet JM, Ducimetiere P, Claude JR. Is the level of serum triglyceride a significant predictor of coronary death in “normocholesterolemic” subjects? The Paris prospective study. Am J Epidemiol 1986; 124: 624-632
• 3 Austin MA. Plasma triglyceride as a risk factor for coronary heart disease. The epidemiologic evidence and beyond. Am J Epidemiol 1989; 129: 249-259
• 4 Carvalho ACA, Colman RW, Lees RS. Platelet function in hyperlipoproteinemia. N Engl J Med 1974; 290: 434-438
• 5 Zahavi J, Betteridge JD, Jones NAG, Galton DJ, Kakkar VV. Enhanced in vivo platelet release reaction and malondialdehyde formation in patients with hyperlipidemia. Am J Med 1981; 70: 59-65
• 6 Aviram M, Brook GJ. The effect of human plasma on platelet function in familial hypercholesterolemia. Thromb Res 1982; 26: 101-109
• 7 Colli S, Lombroso M, Madema P, Tremoli E, Nicosia S. Effect of PGI₂ on platelet aggregation and adenylate cyclase activity in human type IIA hypercholesterolemia. Biochem Pharmacol 1983; 32: 1989-1993
• 8 Tremoli H, Maderna P, Colli S, Morazzoni G, Sirtori M, Sirtori S. Increased platelet sensitivity and thromboxane B₂ formation in type-II hyperlipoproteinemic patients. Eur J Clin Invest 1984; 14: 329-333
• 9 Strobl-Jäger E, Widhalm K, Sinzinger H. Influence of type IIa, IIb and IV-hyperlipoproteinemia on platelet prostaglandin sensitivity, plasma thromboxane B₂ and platelet half-life. Prostagl Leukotr Med 1986; 25: 39-47
• 10 Croft KD, Beilin LJ, Vandongen R, Rouse I, Masarei J. Leukocyte and platelet function and eicosanoid production in subjects with hypercholesterolaemia. Atherosclerosis 1990; 83: 101-109
• 11 Malle E, Gries A, Kostner GM, Pfeiffer K, Nimpf J, Hermetter A. Is there any correlation between platelet aggregation, plasma lipoproteins, apoproteins and membrane fluidity of human blood platelets?. Thromb Res 1989; 53: 181-190
• 12 Muller S, Ziegler O, Donner M, Drouin P, Stoltz JF. Rheological properties and membrane fluidity of red blood cells and platelets in primary hyperlipoproteinemia. Atherosclerosis 1990; 83: 231-237
• 13 Duhm J, Behr J. Role of exogenous factors in alterations of red cell Na⁺-Li⁺ exchange and Na+-K+ cotransport in essential hypertension, primary hyperaldosteronism, and hypokalemia. Scand J Lab Invest 1986; Suppl 180: 83-95
• 14 Williams RR, Hunt SC, Hopkins PN. Familial dyslipidemic hypertension. Evidence form 58 Utah families for a syndrome present in approximately 12% of patients with essential hypertension. J Am Med Assoc 1988; 259: 3579-3586
• 15 Hespel P, Lijnen P, Fagard R, M’Buyamba-Kabangu JR, Van Hoof R, Lissens W, Rosseneu M, Amery A. Changes in erythrocyte sodium and plasma lipids associated with physical training. J Hypertension 1988; 6: 159-166
• 16 Nyrop M, Zweifler AJ. Platelet aggregation in hypertension and the effect of the antihypertensive treatment. J Hypertension 1988; 6: 263-269
• 17 De Clerck F. Blood platelets in human essential hypertension. Agents Actions 1985; 18: 563-580
• 18 Shattil SJ, Anaya-Galindo R, Bennett J, Colman RW, Cooper RA. Platelet hypersensitivity induced by cholesterol incorporation. J Clin Invest 1975; 55: 636-643
• 19 Valtier D, Guicheney P, Baudouin-Legros M, Meyer P. Platelets in human essential hypertension: in vitro reactivity to thrombin. J Hypertension 1986; 5: 551-555
• 20 Stuart MJ, Gerrard JM, White JG. Effect of cholesterol on production of thromboxane B₂ by platelets in vitro. N Engl J Med 1980; 302: 6-10
• 21 Erne P, Bolli P, Burgisser FR, Bühler FR. Correlation of platelet calcium with blood pressure. Effect of an antihypertensive therapy. N Engl J Med 1984; 310: 331-332
• 22 Le Quan Sang KH, Levenson J, Simon A, Meyer P, Devynck MA. Platelet cytosolic free Ca²⁺ concentration and plasma cholesterol in untreated hypertension. J Hypertension 1987; 5 (Suppl. 05) S251-S254
• 23 Locher R, Knorr M, Edmonds D, Neyses L, Vetter W. Influence of cholesterol on intracellular free calcium concentration in human platelets. J Hypertension 1986; 4 (Suppl. 06) S358-S360
• 24 Dimitrov D, Resink TJ, Müller FB, Bühler FR. Altered platelet phosphatidylinositol metabolism in essential hypertension. J Hypertension 1986; 4 (Suppl. 06) S346-S348
• 25 Heagerty AM, Ollerenshaw JD. The phosphoinositide signalling system and hypertension. J Hypertension 1987; 5: 515-524
• 26 Kramer RM, Jakubowski A, Vaillancourt R, Deykin D. Effect of membrane cholesterol on phospholipid metablism in thrombin-stimulated platelets. J Biol Chem 1982; 257: 6844-6849
• 27 Shastri KM, Carvalho ACA, Roberts RS. Platelet function and platelet lipid composition in the dyslipoproteinemias. J Lipid Res 1980; 21: 467-472
• 28 Benjamin N, Graham JM, Robinson BF, Wilson RBJ. Cholesterol/phospholipid ratio is increased in the plasma membrane of platelets from patients with primary hypertension. J Hypertension 1988; 6 (Suppl. 04) S706-S707
• 29 Naftilan AJ, Dzau VJ, Loscalzo J. Preliminary observations on abnormalities of membrane structure and function in essential hypertension. Hypertension 1986; 8 (Suppl. 02) II: 174-179
• 30 Le Quan Sang KH, Montenay-Garestier R, Devynck MA. Alterations of platelet membrane microviscosity in essential hypertension. Clin Sci 1991; 80: 205-211
• 31 Shattil SJ, Cooper RA. Membrane microviscosity and human platelet function. Biochemistry 1976; 15: 4832-4837
• 32 Prendergast FG, Haugland RP, Callahan PJ. 1-[4-(Trimethylamino)phenyl]-6-phenylhexa-1, 3, 5-triene: synthesis, fluorescence properties, and use as a fluorescence probe of lipid bilayers. Biochemistry 1981; 20: 7333-7338
• 33 Ellefson RD, Caraway WT. Blood lipids. In: Fundamentals of Clinical Chemistry. Trietz NW. (ed). WB Saunders Co; Philadelphia, PA: 1982: 509-510
• 34 Le Quan Sang KH, Devynck MA. Increased platelet cytosolic free calcium in essential hypertension. J Hypertension 1986; 4: 564-574
• 35 Astarie C, Levenson J, Simon A, Meyer P, Devynck MA. Platelet cytosolic proton and free calcium concentrations in essential hypertension. J Hypertension 1989; 7: 485-491
• 36 Mazeaud MM, Le Quan Sang KH, Devynck MA. Platelet cyclic AMP in essential hypertension. J Hypertension 1989; 7: 501-506
• 37 Muggli R, Tschopp TB, Mittelholzer E, Baumgartner HR. 7-bromi-1,5-dihydro-3,6-dimethylimidazo(2,1-b)quinazolin-2(3H)-one (Ro 15-2041), a potent antithrombotic agent that selectively inhibits platelet cyclic AMP-phosphodiesterase. J Pharmacol Exp Ther 1985; 235: 212-219
• 38 Born GVR. Aggregation of blood platelets by adenosine and its reversal. Nature 1962; 195: 927-935
• 39 Levin RI, Weksler BB, Jaffe EA. The interaction of sodium nitroprusside with human endothelial cells and platelets: nitroprusside and prostacyclin synergistically inhibit platelet function. Circulation 1982; 66: 1299-1307
• 40 Folch J, Lees M, Sloane-Stanley GH. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957; 226: 497-509
• 41 Rouser G, Fleischer S, Yamamoto A. Two dimensional thin layer chromatography separation of polar lipids and determination of phospholipids by phosphorus analysis of spots. Lipids 1970; 5: 494-496
• 42 Aviram M, Brook JG. Platelet interaction with high and low density lipoproteins. Atherosclerosis 1983; 46: 259-268
• 43 Shinitzky M. Membrane fluidity and cellular functions. In: Physiology of Membrane Fluidity. Shinitzky M. (ed). CRC Press Inc; Boca Raton, FL: 1984. 1 1-51
• 44 Aviram M, Williams KJ, Deckelbaum RJ. Macrophage cholesterol removal by triglyceride-phospholipid emulsions. Biochem Biophys Res Commun 1988; 155: 709-713
• 45 Berlin E, Bhathena SJ, Judd JT, Nair PP, Jones DY, Taylor PR. Dietary fat and hormonal effects on erythrocyte membrane fluidity and lipid composition in adult women. Metabolism 1989; 38: 790-796
• 46 Mazeaud M, Driss F, Le Quan Sang KH, Duranthon V, Levenson J, Simon A, Devynck MA. Biochemical and functional alterations associated with hypercholesterolemia in platelets from hypertensive patients. Atherosclerosis 1992; 94: 201-211
• 47 Astarie C, Le Quan Sang KH, David-Dufilho M, Devynck MA. Further investigations on platelet cytosolic alkalinization in essential hypertension. J Hypertension 1992; 10: 849-854