Platelet Membrane Lipid Composition Research Articles

Condition of platelet factor of hemostasis system in pathogenesis of chronic periodontitis progression

Аim. Тo evaluate the structural and functional condition of platelets as a cellular component of the hemostasis system in chronic generalized periodontitis of different severity, and to establish its role in the progression of the disease.
 Materials and Мethods. Clinical studies included 83 patients (47 men and 36 women) with chronic generalized periodontitis, comparable in age and sex, divided into three groups according to the severity of the disease: the first group (n=21) – periodontitis of mild severity; the second group (n=36) – moderate degree of severity; the third group (n=26) – severe periodontitis. Methods of the study included evaluation of the structural and functional characteristics of periodontal tissues, general hygienic condition of the oral cavity, the severity of the inflammatory process according to index parameters; study of microcirculation of periodontal tissues, determination of the evidence of oxidative processes in saliva, blood plasma, platelets, study of lipid composition of platelets.
 Results. In chronic generalized periodontitis, pathological changes in the lipid composition of platelet membranes (an increase in the percentage of lysophospholipids and free fatty acids) were associated with systemic activation of oxidative processes and of phospholipase enzyme systems, which was accompanied by an increase in their aggregation activity.The degree of increase in the activity of platelets was associated with the severity of microcirculatory disturbances in the periodontal tissues. The condition of the cellular component of the hemostasis system correlated with the severity of the pathological process in the periodontium. In severe degree of chronic periodontitis, structural and functional changes in platelets were maximal.
 Conclusion. In chronic periodontitis, the systemic activation of oxidative processes leads to a modification of the lipid composition of platelet membranes, which contributes to increase in their aggregation activity playing an important role in the induction of hypercoagulation, microcirculation disturbances and progression of inflammation in the periodontal tissues.

ATP‐binding cassette transporter 1 (ABCA1) deficiency decreases platelet reactivity and reduces thromboxane A2 production independently of hematopoietic ABCA1

ESSENTIALS: The role of ATP-binding cassette transporter 1 (ABCA1) in platelet functions is poorly characterized. We studied the impact of ABCA1 deficiency on platelet responses in a mouse model and two Tangier patients. ABCA1-deficient platelets exhibit reduced positive feedback loop mechanisms. This reduced reactivity is dependent on external environment and independent of hematopoietic ABCA1. The ATP-binding cassette transporter ABCA1 is required for the conversion of apolipoprotein A-1 to high-density lipoprotein (HDL), and its defect causes Tangier disease, a rare disorder characterized by an absence of HDL and accumulation of cholesterol in peripheral tissues. The role of ABCA1 in platelet functions remains poorly characterized. To determine the role of ABCA1 in platelet functions and to clarify controversies concerning its implication in processes as fundamental as platelet phosphatidylserine exposure and control of platelet membrane lipid composition. We studied the impact of ABCA1 deficiency on platelet responses in a mouse model and in two Tangier patients. We show that platelets in ABCA1-deficient mice are slightly larger in size and exhibit aggregation and secretion defects in response to low concentrations of thrombin and collagen. These platelets have normal cholesterol and major phospholipid composition, granule morphology, or calcium-induced phosphatidylserine exposure. Interestingly, ABCA1-deficient platelets display a reduction in positive feedback loop mechanisms, particularly in thromboxane A2 (TXA2) production. Hematopoietic chimera mice demonstrated that defective eicosanoids production, particularly TXA2, was primarily dependent on external environment and not on the hematopoietic ABCA1. Decreased aggregation and production of TXA2 and eicosanoids were also observed in platelets from Tangier patients. Absence of ABCA1 and low HDL level induce reduction of platelet reactivity by decreasing positive feedback loops, particularly TXA2 production through a hematopoietic ABCA1-independent mechanism.

Response of Northern Elephant Seal platelets to pressure and temperature changes: A comparison with human platelets

Mammalian blood platelets are activated by physiological agonists such as collagen or thrombin, or by physical stimuli such as cold temperatures and rapid decompression. Marine mammals regularly experience cold temperatures, high pressures and rapid decompression while diving, yet do not appear to suffer from thrombotic events during routine dive activity. We evaluated the effects of cold temperature and high pressure excursions on Northern Elephant Seal (NES) platelets and compared NES platelet response to that of human platelets subjected to identical stimuli. NES platelets undergo cold-induced activation when chilled to 4°C, and 3 distinct phase transitions can be measured using Fourier Transform Infrared Spectroscopy. NES platelet membrane lipid composition was determined using thin layer chromatography and NES platelets were found to have three times the amount of cholesterol (21% by weight) as human platelets. When exposed to high pressure-rapid decompression excursion, NES platelets did not undergo morphological shape change nor bind increased amounts of fibrinogen, while human platelets were significantly activated by the same excursion. These results demonstrate that while NES platelets are activated by the physical stimulus of cold temperatures, they are resistant to decompression-induced activation. We suggest that the composition of NES platelet membranes may play an important role in preventing pressure-related activation.

Bruising and the ketogenic diet: evidence for diet-induced changes in platelet function.

Excessive bruising is a symptom noted by parents of some children treated with the ketogenic diet for epilepsy control, although this side effect is not reported in the literature. We evaluated our cohort of current and past diet-treated patients for symptoms of bruising or bleeding through chart review and prospective screening at clinic follow-up visits. A significant increase in bruising or other minor bleeding was reported and/or observed in 16 of 51 patients (31.4%). There were no differences in sex distribution or number of anticonvulsants used between patients with bruising/bleeding and those without this symptom, although the group with bruising/bleeding was significantly younger. No specific anticonvulsant was associated with bruising/bleeding. Six patients with diet-induced bruising/bleeding underwent an investigation for bleeding diathesis. Five of these patients had prolonged bleeding times and all had diminished responsiveness to various platelet aggregating agents, with no evidence of a release defect. The abnormalities all normalized in the 1 patient tested after ceasing the diet. No patients had serious hemorrhage. One patient had mild von Willebrand disease, which had been asymptomatic before diet initiation. Some patients were Stimate responsive, suggesting a treatment for more severe bouts of symptoms. These data suggest that a ketogenic diet-related bleeding tendency occurs in about one third of treated patients owing to preexisting factors defining susceptibility in combination with diet-induced depression of platelet responsiveness, possibly related to changes in platelet membrane lipid composition and/or concentration and resultant effects on function of membrane-embedded proteins. Patients on the diet undergoing anticoagulation or surgery should be evaluated carefully for symptoms of bleeding tendency.

Lipid composition of platelets in patients suffering from migraine without aura.

Patients with migraine have a platelet hyperaggregability. As this alteration could be the consequence of an abnormal lipid composition of platelet membranes, we studied the phospholipid specimens and the cholesterol/phospholipid ratio in platelet of neuron patients suffering from migraine. The cholesterol/phospholipid ratio was 0.7 +/- 0.1 (normal 0.6 +/- 0.1, molar ratio). The proportion of five main platelet phospholipids components including phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, and phosphatidylinositol, were also normal. These data suggest that platelet hyperactivity in patients with migraine is not due to an altered lipid content of those cells.

An Abnormal Platelet Membrane Lipid Composition in Patients with Low and High Blood Cholesterol

Platelet lipid composition was determined in subjects with hypercholesterolemia (HC) (9.17 ± 2.15 mmol/L), hypocholesterolemia (HYPOC) (3.29 ± 1.01 mmol/L), and normocholesterolemic controls (NC) (5.29 ± 0.82 mmol/L). Lipid composition was quantitated in washed platelets by measuring platelet cholesterol (C) and phospholipid (PL) content, C/PL molar ratio and platelet PL phosphatidylcholine (PC) to sphingmyelin (SM) ratio. There was a significant increase and a significant decrease in C/PL molar ratio in subjects with HC and HYPOC compared to normals (0.74 ± 0.06 and 0.53 ± 0.06 vs 0.59 ± 0.04, p<0.01, respectively). These alterations were due to a significant change in platelet C content, whereas, platelet PL content was stable. PC/SM ratio was markedly decreased in HYPOC compared to NC (0.80 ± 0.18 vs 2.03 ± 0.18, p<0.01, respectively). These results indicate that blood cholesterol is a major determinant of platelet membrane lipid composition. This effect may be of concern in relation to a possible excess morbidity in patients not only with HC, but also with a low blood cholesterol.

Platelet thromboxane A2 receptor number and function in normal and hypertensive pregnancy.

Our study evaluated the number and function of platelets for thromboxane A2/prostaglandin H2 (TxA2/PGH2) and the platelet response to TxA2 receptor agonists in normal and hypertensive pregnancy. In addition, correlations between platelet membrane lipid composition and TxA2 receptor number and function were evaluated. Ten normotensive healthy pregnant women (GC), 10 hypertensive pregnant women (PIH), and 10 normotensive nonpregnant healthy women (C) were examined. Radioligand binding and aggregation studies were performed. Lipid composition of platelet membrane was assessed as cholesterol to phospholipids ratio (CH/PL) and normalized to protein content. TxA2/PGH2 receptor binding sites and affinity did not differ among the groups. An enhanced response to TxA2 receptor agonist U46619 in GC and in PIH compared to C was observed, while platelet response to thrombin was not different among the groups. CH/PL was altered in PIH respect to GC and C. No significant correlation was found between CH/PL and number and function of platelet TxA2 receptors in PIH. In PIH there is no alteration of number or function of TxA2 receptors on platelet membrane. However, the enhanced TxA2 production associated with the increased sensitivity of platelet to TxA2 in pregnancy may contribute to the microcirculatory thrombotic changes of PIH.

Effects of synvinolin on platelet aggregation and thromboxane B 2 synthesis in type IIa hypercholesterolemic patients

An increased susceptibility of platelets to aggregation induced by various agents and a higher production of active arachidonate metabolism have been described in type IIa hypercholesterolemia. This study was designed to evaluate whether changes in platelet function could be observed in hypercholesterolemic patients after synvinolin therapy. Administration of synvinolin to 12 type IIa hypercholesterolemic patients for 24 weeks had a lipid lowering effect and resulted in a marked reduction of platelet aggregation and thromboxane formation induced by collagen and arachidonate. Maximum response was achieved at 4–8 weeks and lipid lowering effects at 2 weeks. This finding indicates that platelet changes cannot be explained by a direct effect of synvinolin on platelets, and the antiplatelet response may therefore depend on platelet membrane lipid composition changes, particularly in the platelet cholesterol content of platelet membranes, following substantial reductions of total plasma cholesterol and LDL-cholesterol.

Altered membrane fatty acid composition and increased thromboxane A 2 generation in platelets from patients with diabetes

Lipid composition of platelet membranes and thromboxane A 2 (TxA 2) generation by platelets were investigated in 42 diabetic patients (14 with macroangiopathic complications, 10 with microangiopathy and 18 without vascular complications) and in 42 clinically healthy subjects of similar age. All subjects were on a similar dietary regimen and the adherence to diet was checked by analysis of red blood cell lipids. Platelets from all groups of diabetic patients produced increased amounts of TxA 2 than platelets from controls (at least p < 0.01) and patients with macroangiopathy produced more TxA 2 than patients without vascular complications and patients with microangiopathy (p < 0.01) Platelet cholesterol and total platelet phospholipids were higher in patients with macroangiopathy, while the relative percentage of the different phospholipid fractions in platelet membrane and their saturated and unsaturated fatty acids were similar in the different groups. Arachidonic acid (AA) content in phosphatidylcholine (PC) was found to be significantly higher in diabetic patients than in controls (at least p < 0.005). Moreover patients with macroangiopathy had higher AA (p < 0.001) and lower eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) levels in PC (p < 0.001) than the other groups of patients and controls.

Increased thromboxane a2 generation and altered membrane fatty acid composition in platelets from patients with active angina pectoris

Lipid composition of platelet membranes and thromboxane A2 (TxA2) generation by platelets were investigated in eighty-seven anginal patients (forty-two with resting angina in active phase and forty-five with effort stable angina or rest angina in inactive phase) and in forty-five clinically healthy subjects of similar age. All subjects were on the same dietary regimen and the adherence to diet was checked by analysis of red blood cell lipids. Platelets from active angina patients produced more TxA2 than platelets from both inactive patients and controls (p<0.001). Moreover patients with active angina had higher arachidonic acid (AA, p<0.001) and lower eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) levels in phosphatidylcholine (PC, p<0.001), than inactive patients and controls. AA and EPA changes in membrane PC significantly correlated with TxA2 production (p<0.001) but not with coronary pathoanatomy. Plasma lipids, content of cholesterol, total phospholipids (and their saturated and unsaturated fatty acids) and the different phospholipid fractions in platelet membrane were not different in the three groups. Present results indicate that in platelets from anginal patients phospholipid fatty acid composition is at least in part independent of plasma composition and that in active angina there are modifications leading to increased TxA2 formation and possibly contributing to the occurrence of ischemic attacks.

Platelet membrane lipid composition and the frequency of migraine.

SYNOPSIS A variety of evidence associates abnormalities in platelet function with the development of migraine. Given the pivotal role of platelet membranes in these functions, it was proposed that migraine patients have abnormalities in their platelet membrane composition. To examine this hypothesis, platelet membrane lipid composition was analyzed in 16 migraine patients and 10 control subjects. The content of phosphatidylcholine, the amount of arachidonic acid in phosphatidylcholine, and the amount of unsaturated fatty acids in most phospholipids were significantly increased in patients with infrequent migraine as compared to controls or patients with frequent migraine. These results suggest that membrane lipid composition may play a role in the frequency and severity of migraine attacks.

Inhibition of Platelet Aggregation by Ethanol in Vitro Shows Specificity for Aggregating Agent Used and Is Influenced by Platelet Lipid Composition

Ethanol at physiologically tolerable concentrations inhibited platelet aggregation in vitro in a relatively specific way, which may be influenced by platelet membrane lipid composition. Aggregation to collagen, calcium ionophore A23187 and thrombin (low doses) were often markedly inhibited by ethanol, adrenaline and ADP responses were little affected, and aggregation to exogenous arachidonic acid was actually potentiated by ethanol. Aggregation to collagen, thrombin and A23187 was inhibited more by ethanol in platelets enriched with saturated fatty acids than in those enriched with unsaturated fats. Platelets enriched with cholesterol showed increased sensitivity to ADP, arachidonate and adrenaline but this increase in cholesterol content did not appear to influence the inhibition by ethanol of platelet responses. The results suggest that ethanol may inhibit aggregation by an effect on membrane fluidity and/or calcium mobilization resulting in decreased activity of a membrane-bound phospholipase.