[New governing body of the German Hypertension League].
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Germany↗
Biomedical subjects
W Zidek
Publications and source records attributed to W Zidek.
MRI of the pharynx and treatment efficacy of a mandibular advancement device in obstructive sleep apnoea syndrome.
In obstructive sleep apnoea syndrome (OSAS), prosthetic mandibular advancement devices (MAD) seem to be a promising treatment alternative to conventional continuous positive airway pressure therapy. Unfortunately, while they are effective in some patients, they are ineffective in others or may even worsen OSAS. At present, it is not known whether predictors can be defined which allow for estimation of the potential effect of oral appliances on the severity of OSAS. Clinical and polysomnographical efficacy of a MAD was evaluated in 15 patients with OSAS. In addition, ultrafast magnetic resonance imaging (MRI) of the pharynx was performed in 13 of these patients at rest during transnasal shallow respiration and during performance of the Muller manoeuvre, both with and without the MAD, and the site of closure was determined. The MAD reduced the mean apnoea/hypopnoea index (AHI) from 19.8+/-14.5 to 7.2+/-7.4 x h(-1). Seven subjects (53.8%) had at least a 50% reduction in AHI to a value <10 x h(-1) with the MAD, whereas the MAD was ineffective in six patients. Five of the seven treatment responders had no significant pharyngeal obstruction during the manoeuvre with the device, while all of them had pharyngeal obstruction when not equipped with the device. Four of the six patients with treatment failure had a single velopharyngeal obstruction and two a combined obstruction of the velo- and glossopharynx during the Muller manoeuvre while wearing the device. The results of this study suggest that airway patency during the Muller manoeuvre while wearing a mandibular advancement device may be predictive of the success of obstructive sleep apnoea syndrome treatment with a mandibular advancement device.
Adult↗
[New guidelines in hypertension. What is relevant for general practice?].
The latest guidelines aim to help improve the diagnosis and treatment of hypertension. This purpose is served by the following recommendations: Blood pressure values of 140/90 must already be considered to signal hypertension. Normotension in turn, is subdivided into optimal, normal and high-normal blood pressure. This is relevant in particular to certain high risk groups, for whom an appreciable lowering of blood pressure is associated with a further decrease in mortality. Particular attention is warranted in isolated systolic hypertension, which represents a cardiovascular risk that should not be underestimated. Every hypertensive should undergo a basic examination during which pointers to secondary hypertension must be investigated. Evidence-based, non-medication measures include weight reduction, salt restriction, reduction of alcohol use, and regular "endurance" exercise. The selection of antihypertensive drugs should be determined by concomitant diseases. All in all, the therapeutic strategy will be increasingly be oriented to such additional risk factors as diabetes mellitus, dyslipidemia or already present organic damage.
Adult↗
Sleep-Disordered breathing in patients referred for angina evaluation--association with left ventricular dysfunction.
BACKGROUND: Clinical observations have linked sleep-disordered breathing to cardiovascular morbidity and mortality, and especially to coronary artery disease. HYPOTHESIS: The study was undertaken to determine the prevalence of sleep-disordered breathing in consecutive patients referred for angina evaluation, and analyzed the parameters influencing the severity of sleep-disordered breathing. METHODS: In all, 68 consecutive patients (53 men, 15 women, aged 63.4 +/- 10.0 years) referred for angina evaluation were studied. Coronary angiography, selective left ventriculography, and a polygraphic study with a validated six-channel monitoring device were performed. Full-night polysomnography was used to reevaluate patients with an apnea/hypopnea index > or = 10/h. RESULTS: Sleep-disordered breathing as defined by an apnea/hypopnea index > or = 10/h was found in 30.9% of patients; its prevalence was not increased in patients with and without coronary artery disease (26.5 vs. 42.1%). Multiple stepwise linear regression analysis revealed that the severity of sleep-disordered breathing was significantly and independently associated with left ventricular ejection fraction (r = -0.38; p = 0.002), but not with age, body mass index, gender, diabetes mellitus, hypertension, hyperuricemia, hypercholesterolemia, smoking habits, or coronary artery disease. In this group of patients, multiple logistic regression analysis could not demonstrate sleep-disordered breathing to be an independent predictor of coronary artery disease. CONCLUSIONS: Sleep-disordered breathing is common in patients referred for angina evaluation. The degree of sleep-disordered breathing is mainly determined by the extent of left ventricular dysfunction.
Angina Pectoris↗
Mass-spectrometry-linked screening of protein fractions for enzymatic activities--a tool for functional genomics.
A simple and rapid strategy is described to screen protein fractions for defined enzymatic activity. A protein fraction from a porcine kidney extract was immobilized by covalent coupling to activated affinity beads. The immobilized proteins were incubated with probes specific for different enzyme activities. The reaction products were analyzed by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. The MALDI spectra indicate the presence of 5'-nucleotidase, phosphatase, kinase, glutathione reductase, and renin activities in the kidney protein extract. Furthermore, the method can be used to screen for inhibitors of enzymatic reactions. The method is adaptable to high-throughput sample handling and automated mass spectrometric analysis and therefore suited for functional genomics.
Animals↗
CoenzymeA glutathione disulfide is a potent modulator of angiotensin II-induced vasoconstriction.
CoenzymeA glutathione disulfide (CoASSG) has recently been isolated from bovine adrenal glands and is assumed to play an important role in blood pressure (BP) control. We used the isolated perfused rat kidney to investigate the modulating effects of CoASSG on angiotensin II (AngII)-induced vasoconstriction. Permanent perfusion with CoASSG (1 micromol/L) for 60 min induced a significant (P < .05) shift to the left in the dose-response curve for AngII (about 3.1-fold), whereas the dose-response curve for norepinephrine (NE) was unaffected. During continuous perfusion with 1 micromol/L CoASSG, the repetitive application of 10 pmol AngII significantly increased its vasoconstriction by 170% +/- 14% (P < .05) and 235% +/- 50% (P < .05) for 60 and 120 min, respectively. The potentiation of AngII by permanent perfusion with CoASSG is dose- and time-dependent and shows a plateau at 120 min. Glutathione, oxidized coenzymeA, and coenzymeA (each 1 micromol/L) are not able to enhance the vasoconstriction induced by AngII. We conclude that CoASSG is able to potentiate the vasoactive properties of AngII, and that CoASSG might play an important role in BP regulation via modulating effects of AngII.
Angiotensin II↗
The critical role of adenosine and guanosine in the affinity of dinucleoside polyphosphates to P(2X)-receptors in the isolated perfused rat kidney.
1. The activation of P(2x)-receptors in the rat renal vasculature by dinucleoside polyphosphates with variable phosphate group chain length (Xp(n)X; X=Adenin (A) /Guanin (G), n=4 - 6) was studied by measuring their effects on perfusion pressure of the isolated perfused rat kidney at constant flow in an open circuit. 2. Like Ap(4)A, Ap(5)A and Ap(6)A the dinucleoside polyphosphates Ap(4)G, Ap(5)G and Ap(6)G exerted a vasoconstriction which could be blocked by suramin and pyridoxal-phosphate-6-azophenyl-2; 4-disulphonic acid (PPADS). 3. Gp(4)G, Gp(5)G and Gp(6)G showed only very weak vasoconstriction at high doses. 4. Ap(6)A and alpha, beta-meATP could not be blocked by the selective P(2x1)-receptor antagonisten NF023 (30 microM), whereas Ap(4)A, Ap(4)G, Ap(5)A, Ap(5)G and Ap(6)G were partially blocked by NF023. 5. Inhibition of endothelial NO-synthase by N(omega)-nitro-L-arginine methyl ester (L-NAME) did not affect vasoconstrictions induced by dinucleosidepolyphosphates. 6. P(2x)-receptor can only be activated if at least one adenosine moiety is present in the molecule. 7. Ap(n)G show a weaker vasoconstrictive action than corresponding Ap(n)A, concluding that two adenosine moieties enhance the P(2x)-receptor binding and activation. 8. Xp(n)X containing five phosphate groups show the most pronounced vasoconstrictive effect whereas four phosphate groups show the less effect, therefore the number of phosphate groups critically changes receptor affinity. 9. Additional experiments using permanent perfusion with alpha, beta-methylene ATP (alpha,beta-meATP) and the selective P(2x1)-receptor antagonist NF023 showed that the newly discovered human dinucleoside polyphosphates activated the vascular P(2x1)-receptor and an recently identified new P(2x)-receptor subtype. 10. The differential effects of dinucleoside polyphosphates allow a fine tuning of local perfusion via composition of Xp(n)Xs.
Adenosine↗
Increased vascular growth in hemodialysis patients induced by platelet-derived diadenosine polyphosphates.
BACKGROUND: Enhanced vascular smooth muscle cell (VSMC) growth is one hallmark of atherosclerosis. One mechanism responsible for stimulating arterial smooth muscle cell growth is the release of growth factors from platelets aggregating at endothelial lesions. Since in end-stage renal failure (ESRF) atherogenesis is markedly accelerated, the release of VSMC growth factors on aggregation of platelets from hemodialysis patients, ESRF patients in the predialysis stage, and healthy subjects was examined. METHODS: Platelets were activated by thrombin, and the supernatant was tested for growth stimulation in VSMCs from rat aorta. The cell proliferation rate was determined by [(3)H]-thymidine incorporation in VSMCs. The diadenosine polyphosphate (Ap(n)A with N = 3 to 6) content in the supernatant and in intact platelets was determined using a chromatographic assay established on the basis of affinity- and reversed-phase chromatographic methods. RESULTS: The thrombin-activated platelet supernatant from hemodialysis patients (N = 15) increased the [(3)H]-thymidine incorporation rate in VSMC s in comparison to the supernatant of healthy control subjects (N = 17, counts/supernatant of 10(6) stimulated platelets +/- SEM, 604 +/- 71 vs. 364 +/- 45, P < 0.05). The addition of the selective P2-receptor blocker pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid to supernatants inhibited the stimulatory effects of Ap(n)A on the growth of vascular smooth muscle cells (219 +/- 53 vs. 156 +/- 71 counts/supernatant of 106 stimulated platelets +/- SEM). The Ap(n)A (N = 3 to 6) amount of thrombin-activated platelet supernatants from hemodialysis patients was significantly higher than in platelets from 10 healthy control subjects (Ap(3)A, 119 +/- 32 vs. 12 +/- 3; Ap(4)A, 154 +/- 59 vs. 43 +/- 20; Ap(5)A, 39 +/- 14 vs. 13 +/- 6; Ap(6)A, 42 +/- 19 vs. 2 +/- 1 fg/platelet +/- SEM, each P < 0.05, N = 10). The intracellular Ap(n)A (N = 3 to 6) amount of intact platelets from hemodialysis patients (N = 61) was significantly higher than that from healthy control subjects [N = 30, Ap(n)A amount (fg/platelet +/- SEM): Ap(3)A, 366 +/- 68 vs. 14.7 +/- 1; Ap(4)A, 336 +/- 48 vs. 19 +/- 2; Ap(5)A, 227 +/- 35 vs. 10 +/- 1; Ap(6)A, 141 +/- 45 vs. 4 +/- 1; each P < 0.01]. CONCLUSIONS: The increased amount of dinucleoside polyphosphate in platelets from hemodialysis patients may be an important additional atherogenic factor.
Animals↗
Characterization of p-hydroxy-hippuric acid as an inhibitor of Ca2+-ATPase in end-stage renal failure.
Characterization of p-hydroxy-hippuric acid as an inhibitor of Ca2+-ATPase in end-stage renal failure. In patients with end-stage renal failure (ESRF), disturbances of Ca2+ metabolism are common. Besides hormonal changes, inhibition of cellular Ca2+-ATPase was postulated to contribute to uremic toxicity. We purified a potent inhibitor of the Ca2+-ATPase from the ultrafiltrate of patients with ESRF by multiple steps of high-performance liquid chromatography to homogeneity, and identified the isolated inhibitor by mass spectrometric methods as p-hydroxy-hippuric acid. The enzyme used for the Ca2+-ATPase assay system was isolated from red blood cells by cross-flow filtration. The activity of the Ca2+-ATPase was measured spectrophotometrically as the difference in hydrolysis of adenosine 5'-triphosphate (ATP) in the presence and absence of Ca2+ with different concentrations of ATP and p-hydroxyhippuric acid. The Ca2+-ATPase was found to be inhibited by p-hydroxy-hippuric acid at a concentration above 11.7 micromol/L. p-Hydroxyhippuric acid inhibited the erythrocyte Ca2+-ATPase by reducing Vmax and increasing the Km value. The EC50 (log mol/L; mean +/- SEM) for p-hydroxy-hippuric acid was calculated as 4.82 +/- 0.14. In conclusion, p-hydroxy-hippuric acid may play a role in disturbed Ca2+ metabolism in end-stage renal failure.
Calcium-Transporting ATPases↗
Vasoactive diadenosine polyphosphates in human placenta: possible candidates in the pathophysiology of pre-eclampsia?
BACKGROUND: One hypothesis of the pathophysiology of pre-eclampsia is that placentally derived, yet unidentified, vasoactive factors are released into the maternal circulation, causing hypertension. OBJECTIVE: To determine if diadenosine polyphosphates, new potent vasoconstrictors, are present in human placenta. METHODS AND RESULTS: Human placental tissue was homogenated and fractionated by size-exclusion chromatography, affinity chromatography, anion-exchange chromatography and reversed-phase chromatography. In fractions purified to homogeneity, diadenosine diphosphate, diadenosine triphosphate, diadenosine tetraphosphate, diadenosine pentaphosphate, diadenosine hexaphosphate and diadenosine heptaphosphate were identified by matrix-assisted laser desorption/ionization mass spectrometry, retention-time comparison and enzymatic cleavage analysis. CONCLUSIONS: The presence of diadenosine polyphosphates in human placenta makes them possible candidates for involvement in the pathophysiology of pre-eclampsia. However, their contribution to the pathophysiology of eclampsia requires substantiation in further studies.
Blood Vessels↗
Acetylcysteine for radiocontrast nephropathy.
Radiocontrast nephropathy may in part be mediated by generation of reactive oxygen species causing direct toxic damage to renal tubular epithelial cell and renal medullary ischemia. Data from experimental studies indicated that antioxidants, eg, acetylcysteine, may prevent radiocontrast-induced nephropathy. Recently, one prospective, randomized, placebo-controlled study in patients with moderate renal insufficiency confirmed that the prophylactic oral administration of acetylcysteine at a dose of 600 mg twice daily along with hydration prevents the reduction in renal function by a nonionic, low-osmolality radiocontrast agent.
Acetylcysteine↗
Effect of continuous positive airway pressure therapy on infectious complications in patients with obstructive sleep apnea syndrome.
BACKGROUND: Nasal continuous positive airway pressure (CPAP) is a well-established, widely used and effective treatment of obstructive sleep apnea syndrome (OSAS). Unfortunately, side effects are frequent during CPAP treatment. OBJECTIVES: Little is known about the effects of CPAP on infectious complications in patients with OSAS. METHODS: We retrospectively analyzed the kinds and rate of infections of the upper airway in 246 consecutive patients (mean age, 59.7 years) with polysomnographically verified OSAS using CPAP with or without a heated humidifier and compared them with OSAS patients who received non-CPAP therapy. RESULTS: Of the 246 patients, 40 received conservative therapy and 206 CPAP treatment, 36 of them with a heated humidifier. The mean follow-up period of the study group was 165.4 +/- 92.1 weeks and did not differ between the three groups. Infectious diseases were frequent in all three groups, but patients using CPAP without humidifier suffered from upper airway infections significantly more frequently than controls (42.9 vs. 25%; p < 0.05), and more patients on CPAP therapy with humidifier than controls (22.2 vs. 2.5%; p < 0.01) reported an increased rate of upper airway infections since initiation of CPAP therapy or diagnosis of OSAS. Especially patients using a hot water bath humidifier who cleaned their devices inadequately had significantly more upper airway infections since diagnosis (57.1 vs. 20%; p < 0.05) or during the past 6 months (52.4 vs. 13.3%; p < 0.05) than patients who regularly cleaned CPAP machines, humidifiers and ventilatory circuits. CONCLUSIONS: Our results suggest that patients using CPAP therapy either with or without heated humidity seem to be at an increased risk of upper airway infections compared to conservatively treated patients.
Adult↗
Efficacy and tolerability of angiotensin II type 1 receptor antagonists in dialysis patients using AN69 dialysis membranes.
AIMS AND METHODS: Our aim was to evaluate the antihypertensive efficacy and tolerability of angiotensin II type 1 (AT1) receptor antagonists. Valsartan or candesartan cilexetil was administered to 11 dialysis patients with elevated blood pressure. The patients (6 male, 5 female; mean age +/- SD 61+/-11 years) were on regular bicarbonate hemodialysis three times weekly for more than 3 months using acrylonitrile and sodium methallyl sulfonate copolymer (AN69) dialysis membranes. RESULTS: Within 252 days after administration of the AT1 receptor antagonists the systolic blood pressure was significantly reduced from 161+/-13 to 130+/-12 mmHg (p<0.001), whereas the diastolic blood pressure did not change significantly (76+/-8 vs. 71+/-8 mmHg; p>0.05). In addition, heart rate (75+/-7 vs. 80+/-8/min), body weight, and laboratory variables (hemoglobin, creatinine, blood urea nitrogen, serum potassium, serum sodium, serum calcium, and total protein) showed no significant changes. During 1,188 hemodialysis sessions using AN69 membranes, no hypersensitivity reactions occurred after administration of AT1 receptor antagonists. CONCLUSION: The results indicate that once-daily administration of AT1 receptor antagonists efficiently reduces the systolic blood pressure in hemodialysis patients.
Aged↗
Insulin, blood pressure and elevated Na+/H+ exchange activity--novel therapeutic implications.
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Animals↗
Homocyst(e)ine metabolism in hemodialysis patients treated with vitamins B6, B12 and folate.
Hyperhomocyst(e)inemia is commonly accepted as an independent atherosclerotic risk factor. In most hemodialysis patients, serum homocyst(e)ine is markedly elevated and may contribute to premature atherosclerosis in these patients. Whereas the beneficial effect of folate supplementation on serum homocyst(e)ine has been extensively studied, there are less detailed studies on the effects of cobalamin and pyridoxal phosphate alone, or in combination with folate. We examined the effect of a four-week course of intravenous treatment with folate (1.1 mg), cobalamin (1.0 mg), and pyridoxal phosphate (5.0 mg), administered once (group 1), twice (group 2) or thrice (group 3) weekly in 33 hemodialysis patients divided in three groups of 11 patients. All patients were followed for a further four weeks after treatment was stopped. Serum homocyst(e)ine, cobalamin, folate and pyridoxal phosphate, as well as the metabolites of homocyst(e)ine, methylmalonate, 2-methylcitrate and cystathionine, were determined before, during and after treatment. Baseline serum homocyst(e)ine correlated significantly with serum folate (P=0.0149), cobalamin (P=0.0047) and pyridoxal phosphate (P=0.0408). Correlations independent from the other metabolites or vitamins were found for methylmalonate (P=0.003) and folate (P=0.029). All regimens increased serum cobalamin significantly (in group 1 from 444 +/- 215 to 17,303 +/- 11,989 pg/ml, P<0.01; in group 2 from 542 +/- 633 to 44,896 +/- 15,772 pg/ml, P<0.001; in group 3 from 548 +/- 394 to 77,961 +/- 31,546 pg/ml, P<0.001), but did not increase any of the other vitamin levels. Serum homocyst(e)ine was lowered significantly by 39.8% +/- 31.9% (P<0.05) with two and by 30.1% +/- 26.9% (P<0.05) with three vitamin dosages weekly, but not with one dosage weekly. Since methylmalonate is known to be a sensitive marker of cobalamin deficiency, the data support an important influence of cobalamin levels on baseline homocyst(e)ine levels. Increasing cobalamin levels and additional treatment with folate and pyridoxal phosphate 156 may decrease serum homocyst(e)ine in the same way as high doses of folate alone.
Female↗
Selective agonism of group I P2X receptors by dinucleotides dependent on a single adenine moiety.
We have investigated the activity of naturally occurring high-performance liquid chromatography-purified diadenosine polyphosphates (Ap(n)A, n = 5-6), adenosine polyphospho guanosines (Ap(n)G, n = 5-6), and diguanosine polyphosphates (Gp(n)G, n = 5-6) under voltage-clamp conditions at recombinant rat P2X1-4 purinoceptor subtypes expressed in Xenopus laevis oocytes. At rP2X1 and rP2X3 receptors, Ap(n)As and Ap(n)Gs evoked concentration-dependent inward currents. Gp(n)Gs were not active at these receptors. At rP2X2 and rP2X4 receptors, dinucleotides did not show significant activity. For the rP2X1 receptor, Ap(n)As and Ap(n)Gs were partial agonists; for the P2X3 receptor, only Ap5G was full agonist, whereas the other tested substances were partial agonists. The rank order of potency at rP2X1 was ATP > or = Ap6A > or = Ap5A > or = Ap6G > or = Ap5G, and rank order of efficacy was ATP > or = Ap5A > or = Ap6A > Ap5G > Ap6G, whereas at rP2X3 the rank order of potency was ATP > Ap5G > or = Ap5A > or = Ap6A > or = Ap6G and the rank order of efficacy was ATP approximately Ap5G > or = Ap5A approximately Ap6A > or = Ap6G. For rP2X1 and rP2X3 it is evident that receptor agonism depended on the presence of at least one adenine moiety in the dinucleotide, while the presence of a guanine moiety had a significant impact and decreased agonist efficacy. The data suggest that naturally occurring Ap(n)As and Ap(n)Gs may play an important physiological role in different human tissues and systems by activating group I P2X receptors.
Adenine↗
Dinucleotides as growth-promoting extracellular mediators. Presence of dinucleoside diphosphates Ap2A, Ap2G, and Gp2G in releasable granules of platelets.
Dinucleoside diphosphates, Ap(2)A, Ap(2)G, and Gp(2)G represent a new class of growth-promoting extracellular mediators, which are released from granules after activation of platelets. The presence of theses substances was shown after purification from a platelet concentrate. The substances were identified by UV spectrometry, retention time comparison with authentic substances, matrix-assisted laser desorption/ionization mass spectrometry, post-source-decay matrix-assisted laser desorption/ionization mass spectrometry, and enzymatic analysis. Ap(2)A, Ap(2)G, and Gp(2)G have growth-stimulating effects on vascular smooth muscle cells in nanomolar concentrations as shown by [(3)H]thymidine incorporation measurements. The calculated EC(50) (log m; mean +/- S.E.) values were -6.07 +/- 0.14 for Ap(2)A, -6.27 +/- 0.25 for Ap(2)G, and -6.91 +/- 0.44 for Gp(2)G. At least 61.5 +/- 4.3% of the dinucleoside polyphosphates are released by platelet activation. The intraplatelet concentrations suggest that, in the close environment of a platelet thrombus, similar dinucleoside polyphosphate concentrations can be found as in platelets. Intraplatelet concentration can be estimated in the range of 1/20 to 1/100 of the concentration of ATP. In conclusion, Ap(2)A, Ap(2)G, and Gp(2)G derived from releasable granules of human platelets may play a regulatory role in vascular smooth muscle growth as growth-promoting mediators.
Animals↗
Activation of phosphatidylinositol-specific phospholipase C by HDL-associated lysosphingolipid. Involvement in mitogenesis but not in cholesterol efflux.
Our earlier studies demonstrated that high-density lipoproteins (HDLs) stimulate multiple signaling pathways, including activation of phosphatidylcholine-specific phospholipases C and D (PC-PLs) and phosphatidylinositol-specific phospholipase C (PI-PLC). However, only activation of PC-PLs was linked to the HDL-induced cholesterol efflux. In the study presented here, the role of HDL-induced PI-PLC activation was studied. In human skin fibroblasts, HDL potently induced PI-PLC as inferred from enhanced phosphatidylinositol bisphosphate (PtdInsP(2)) turnover and Ca(2+) mobilization. The major protein component of HDL, apo A-I, did not induce PtdInsP(2) turnover or Ca(2+) mobilization in these cells. Both HDL and apo A-I promoted cellular cholesterol efflux, whereas only HDL induced fibroblast proliferation. Inhibition of PI-PLC with U73122 or blocking intracellular Ca(2+) elevation with Ni(2+) or EGTA markedly reduced the extent of HDL-induced cell proliferation but had no effect on cholesterol efflux. In fibroblasts from patients with Tangier disease which are characterized by defective cholesterol efflux, neither HDL-induced PtdInsP(2) breakdown and Ca(2+) mobilization nor cell proliferation was impaired. HDL-induced fibroblast proliferation, PtdInsP(2) turnover, and Ca(2+) mobilization were fully mimicked by the lipid fraction isolated from HDL. Analysis of this fraction with high-performance liquid chromatography (HPLC) and time-of-flight secondary ion mass spectroscopy (TOF-SIMS) revealed that the PI-PLC-inducing activity is identical with two bioactive lysosphingolipids, namely, lysosulfatide (LSF) and sphingosylphosphorylcholine (SPC). Like native HDL, LSF and SPC induced PtdInsP(2) turnover, Ca(2+) mobilization, and fibroblast proliferation. However, both compounds did not promote cholesterol efflux. In conclusion, two agonist activities are carried by HDL. Apo A-I stimulates phosphatidylcholine breakdown and thereby facilitates cholesterol efflux, whereas LSF and SPC trigger PI-PLC activation and thereby stimulate cell proliferation.
Apolipoprotein A-I↗