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Results for “CARDIOLIPIN”

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PubMed1999

[Cardiolipin antibodies in pregnancy of high risk].

Cardiolipin IgG and IgM antibodies (CAb) were studied in 116 cases of high-risk pregnancy. All the women were undergoing examination or treatment in regional perinatal center. CAb occurred more frequently in antenatal fetal death (50%). In blood hypertension, habitual abortions, history of infertility, gestational gestosis, CAb were encountered in 21.4, 20, 20 and 15.2% of cases, respectively. Intrauterine growth retardation was associated with CAb in 33.3% of cases. CAb occurred in pregnant women of different groups who had high uterine vascular resistance. The above findings indicate CAb contribution to genesis of gestational complications in high risk pregnancy.

Adolescent↗

PubMed2001

Some patients with antiphospholipid syndrome express hitherto undescribed antibodies to cardiolipin-binding proteins.

Contrary to infective anticardiolipin (aCL) antibodies, autoimmune aCL antibodies react with phospholipids (PL) mainly via binding to the plasma glycoprotein cofactor beta2-Glycoprotein I (beta2GPI). While there is a well-documented link between the risk of thrombosis and the presence of beta2GPI-dependent anticardiolipin antibodies, the pathological impact of other antiphospholipid antibodies is less clear. By means of cardiolipin affinity-chromatography, we isolated and identified 3 CL-binding proteins, complement component C4, complement factor H and a kallikrein-sensitive glycoprotein, and tested for the presence of autoantibodies against these proteins in patients with antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE) and other autoimmune diseases. High titers of autoantibodies to C4 as compared to age- and sex-matched healthy controls were present in 3 of 26 patients with APS, and weak titers were found in 2 of 26 patients with SLE and in none of 26 patients with other autoimmune diseases. Autoantibodies to complement factor H were found in 4 APS, 3 SLE and none of the other autoimmune patients. Autoantibodies to kallikrein-sensitive glycoprotein were detected in 6 APS patients, 1 SLE patient, and 1 patient with another autoimmune disease. A close relationship between these antibodies was found, suggesting their origin from a common macromolecular complex. However, no relationship with anti-beta2GPI antibodies was found, with the three patients with higher levels of autoantibodies having a low titer of anti-beta2GPI antibodies. In conclusion, some patients with APS harbor circulating antibodies to other CL-binding proteins which might be useful to further characterize these patients.

Adolescent↗

PubMed2002

Quantitative and compositional study of cardiolipin in platelets by electrospray ionization mass spectrometry: application for the identification of Barth syndrome patients.

BACKGROUND: The concentration of cardiolipin (CL) in cultured skin fibroblasts is a useful indicator of Barth syndrome (BTHS; MIM 302060), but the sampling and culturing of fibroblasts are burdensome and time-consuming procedures. We investigated whether the analysis of CL in platelets might help to identify BTHS in patients suspected of having this condition. METHODS: We used HPLC and online electrospray ionization mass spectrometry (HPLC-ESI-MS) to quantify CL molecular species. The CL content of platelets was studied in blood samples of BTHS and non-BTHS patients. Control blood samples drawn from healthy adults were collected and analyzed within 24 h (n = 10) and 48 h (n = 10) to characterize any effect of sample shipping time on the CL content in platelets. Samples were collected from children 1-10 years of age who were not affected by BTHS (n = 6) and from BTHS patients (n = 4) and analyzed within 24 h. Results for all four groups were compared by a Student t-test for all individual analyses. RESULTS: We found different CL molecular species, e.g., (C18:2)(4)-CL. BTHS patients had a specific decrease of tetralinoleyl-CL concentrations in platelets (0.1-0.5 nmol/mg of protein; n = 4) compared with all control groups (2.3-5.5 nmol/mg of protein; n = 26). Only minor differences were observed among the different control groups. CONCLUSIONS: Quantitative and compositional analyses of CL in platelets by the proposed method allow identification of BTHS patients more rapidly than gene analysis or analysis of CL in cultured skin fibroblasts. The abnormality of CL may explain the abnormal mitochondrial function observed in BTHS. The differences between the control groups did not cause any complication.

Adult↗

PubMed2002

Early changes in intramitochondrial cardiolipin distribution during apoptosis.

Cardiolipin (CL) is essential for the functionality of several mitochondrial proteins. Its distribution between the inner and outer leaflet of the mitochondrial internal membrane is crucial for ATP synthesis. We have investigated alterations in CL distribution during the early phases of apoptosis. Using two classical models (staurosporine-treated HL-60 cells and tumor necrosis factor alpha-treated U937 cells), we found that in apoptotic cells CL moves to the outer leaflet of mitochondrial inner membrane in a time-dependent manner. This occurs before the appearance of apoptosis markers such as plasma-membrane exposure of phosphatidylserine, changes in mitochondrial membrane potential, DNA fragmentation, but after the production of reactive oxygen species. The exposure of a phospholipid on the outer surface during apoptosis thus occurs not only at the plasma membrane level but also in mitochondria, reinforcing the hypothesis of mitoptosis as a crucial regulating system for programmed cell death, also occurring in cancer cells after treatment with antineoplastic agents.

Apoptosis↗

PubMed2003

Inhibition of annexin V binding to cardiolipin and thrombin generation in an unselected population with venous thrombosis.

OBJECTIVE: To examine the effect on annexin V binding to cardiolipin (CL) and in vitro thrombin generation by plasma samples from an unselected population of patients with confirmed venous thrombosis and matched controls. The prevalence of autoimmune antiphospholipid antibodies (aPL) was also determined. METHODS: A total of 111 patients who presented to a single emergency room with symptoms suggestive of venous thromboembolic (VTE) disease were studied. In 34 patients the diagnosis of lower limb deep venous thrombosis (DVT) and/or pulmonary embolus (PE) was confirmed (VTE+ group). In the remaining 77 patients the diagnostic workup was negative (VTE- group). Plasma samples were collected prior to the initiation of anticoagulation and examined for IgG anticardiolipin (aCL), IgG anti-beta2-glycoprotein I (GPI), and IgG anti-prothrombin (aPT antibodies) by ELISA. In addition, the effect of individual patient and control plasma samples on annexin V binding to CL and on in vitro thrombin generation was determined by a competitive ELISA and a chromogenic assay, respectively. RESULTS: The prevalence and levels of IgG aCL, anti-beta2-GPI, and aPT antibodies were similar in the VTE+ and VTE- groups. However, plasma samples from the VTE+ group caused a significant inhibition of in vitro thrombin generation (mean +/- SD Z score: -0.66 +/- 0.97 vs 0.26 +/- 1.46; p < 0.001) and a concurrent but less impressive inhibition of annexin V binding to CL (mean +/- SD Z score: -2.53 +/- 1.44 vs -2.05 +/- 1.61; p = 0.123). Upon analyzing a panel of clinical and laboratory variables, only age and inhibition of thrombin generation were significantly associated with VTE disease. CONCLUSION: Our findings suggest that subtle abnormalities in annexin V physiology may contribute to the procoagulant state in patients with idiopathic venous thrombosis.

Annexin A5↗

PubMed1955

Comparative studies on lecithin as a component of cardiolipin antigens.

Egg-yolk lecithin prepared as described in the second edition of of the WHO monograph on cardiolipin antigens was known to be satisfactory, but documentation was incomplete. In this paper, the authors discuss results of comparisons between egg-yolk lecithin and lecithin of beef-heart origin, carried out in four separate laboratories.

Animals↗

PubMed1992

[Cardiolipin antibodies in acute rheumatic fever].

The paper presented the results obtained in studying the patients with acute rheumatic fever for antibodies to cardiolipin (ACL). The study resulted in the establishment that the development of immunopathies in the presence of acute rheumatic fever combined with the acute streptococcal infection was accompanied by hyperproduction of ACL (more common IgG versus IgM isotypes). The phenomenon mentioned widened the spectrum of acute infectious diseases associated with an increase in ACL synthesis. It was also stated that increased ACL contents were closely related with the involvement of the cardiac valves. Authentic clinical and echocardiological signs of the heart disease were mainly revealed in the patients with high contents of IgG and IgM isotypes of ACL. A certain relationship between the laboratory activity of the disease and ACL hyperproduction was noted as well. The latter permitted the discussion on the impact of streptococcal infection initiating the development of acute inflammation on the hyperproduction of ACL.

Acute Disease↗

PubMed1992

Micelle-assisted protein folding. Denatured rhodanese binding to cardiolipin-containing lauryl maltoside micelles results in slower refolding kinetics but greater enzyme reactivation.

Unfolded (inactive) rhodanese (thiosulfate:cyanide sulfurtransferase, EC 2.8.1.1) can be reactivated in the presence of detergents, e.g. lauryl maltoside (LM). Here, we report the reactivation of urea-unfolded rhodanese in the presence of mixed micelles containing LM and the anionic mitochondrial phospholipid, cardiolipin (CL). Reactivation times increased as the number of CL molecules/micelle was increased. A maximum of 94% of the activity was recovered at 2.2 CL/micelle. Only 71% of the activity was recovered in the absence of CL. The major zwitterionic mitochondrial phospholipid, phosphatidylcholine (PC), had no effect on the LM-assisted reactivation of rhodanese. Size exclusion chromatography showed that denatured, but not native, rhodanese apparently binds to micellar amounts of LM and CL/LM, but not to PC/LM micelles. The lifetime of the enzyme-micelle complex increased with the number of CL molecules/micelle. Furthermore, chromatographic fractions containing micelle-bound enzyme had no activity, while renatured rhodanese-containing fractions were active. These results suggest that transient complexes form between enzyme and both LM and CL/LM micelles, and that this complex formation may be necessary for reactivation. For CL/LM micelles, interactions may occur between the positively charged amino-terminal sequence of rhodanese and the negatively charged CL phosphate. Finally, this work shows that there are similarities between "micelle-assisted" and chaperonin-assisted rhodanese refolding.

Animals↗

PubMed2005

[Effects of Eupolyphaga Sinensis Walker on erythrocyte's CR1 activity and anti-cardiolipin antibody level in rats with stagnation of blood].

AIM: To study the effect of Eupolyphaga Sinensis Walker(ESW) on red blood cell immune adherence (RCIA) and serum anticardiolipin antibody level in rat model of Yin-deficiency Huo-excess with chronic blood stasis. METHODS: The model was made by i.m. injection of dexamethasone (0.5 mg/kg) and adrenaline (0.84 mg/kg). The serum anti-cardiolipin antibodies (ACA) ACA-IgG, ACA-IgA and ACA-IgM and the plasma D-dimmer levels were measured by using enzyme-linked immunosorbent assay (ELISA). The body and organ weight of the rats were measured. RESULTS: For rats of Yin-deficiency Huo-excess, rosette rates of red blood cell C3b receptors (RBC-C3b RR) and red blood cell cancer (RBC-CaR) decreased, the serum ACA-IgG, ACA-IgA, ACA-IgM and the plasma D-dimmer levels markedly increased, body weight and the weight of spleen and thymus all decreased. ESW (5 mg/kg, 10 mg/kg) increased RBC-C3bRR and RBC-CaR, reduced serum ACA-IgG, ACA-IgA, ACA-IgM and plasma D-dimmer levels, and increased spleen weight of the rats. CONCLUSION: ESW can boost the immune function in rats of Yin-deficiency Huo-excess with chronic blood stasis.

Animals↗

PubMed2005

Systemic delivery of RafsiRNA using cationic cardiolipin liposomes silences Raf-1 expression and inhibits tumor growth in xenograft model of human prostate cancer.

Raf-1, a protein serine-threonine kinase, plays a critical role in mitogen-activated protein kinase kinase (MKK/MEK)- mitogen-activated protein kinase (extracellular signal-regulated kinase) (MAPK/ERK) pathways. We show here that systemically delivered novel cationic cardiolipin liposomes (NeoPhectin-AT) containing a small interfering RNA (siRNA) against Raf-1 silence the expression of Raf-1 in tumor tissues and inhibit tumor growth in xenograft model of human prostate cancer. The knockdown of Raf-1 expression by siRNA is also associated with down-regulation of cyclin D1 expression in vivo.

Cardiolipins↗

PubMed1991

[Immobilized granulated drugs with magnetic properties based on nDNA, RNA, cardiolipin in the diagnosis and treatment of systemic lupus erythematosus].

To advance diagnosis and treatment of systemic lupus erythematosus (SLE), the authors have developed a number of specific diagnostic preparations basing on nDNA, RNA, cardiolipin immobilized into the three-dimensional lattice of polyacrylamide gel. Using such granulated antigenic preparations with magnetic properties, a correlation has been derived between SLE activity, visceral pathology and a level of specific antibodies. In view of a successful experimental use of the preparations as selective sorbents, they may be introduced into extracorporeal treatment. Immobilized granulated preparations can be used in immunofluorescent tests and enzyme immunoassays.

Autoantibodies↗

PubMed1991

Comparison of two syphilis antibody assays based on cardiolipin antigen.

Two different antisyphilis screening tests based on cardiolipin antigen, the VDRL test and an RPR test (Sysmic, Diagast), were compared. A total of 2155 sera were examined by both tests. Positive results were confirmed with TPHA and TPI tests. RPR Sysmic test was as sensitive and specific as the VDRL. However, the RPR Sysmic test was easier and quicker, especially when the number of sera tested was high.

Antibodies, Bacterial↗

PubMed1991

Cerebrospinal fluid anti-cardiolipin antibodies in patients with HIV-1 infection.

Both cerebrospinal fluid (CSF) immunologic abnormalities and serum anti-cardiolipin antibodies (aCL) have been reported in patients with HIV-1 infection. The antibody specificity of only a small amount of the total CSF IgG in these patients is known, and is directed against a variety of HIV-1 antigens. The specificity of the remaining CSF IgG is unknown. We report the results of the first study of CSF aCL in an HIV-1-infected population. We measured aCL IgG and IgM in the CSF of 21 HIV-1-infected patients without nervous system symptoms or AIDS, and in four HIV-1-negative controls. Twelve HIV-1-infected patients had an abnormal serum aCL value and CSF immunologic abnormalities and 9 HIV-1-infected patients had either abnormal serum aCL or CSF immunologic abnormalities but not both, or were normal in both regards. There was no difference between any HIV-1-infected patient and controls for CSF aCL IgM. Nine of 12 patients with an abnormal serum aCL and CSF immunologic abnormalities had CSF aCL IgG values that were at least 5 SD above normal control values, whereas none of the remaining patients had abnormal CSF aCL IgG values. All patients with abnormal CSF aCL IgG values had an intact blood-brain barrier as evidenced by an albumin index of less than 9, and all had nonreactive CSF VDRL tests. These data demonstrate that aCL IgG is produced intrathecally in some HIV-1-infected patients.

Adult↗

PubMed1990

Crossreactivity of antibodies directed against cardiolipin, DNA, endothelial cells and blood platelets.

The interrelationship of antibodies directed against cardiolipin (CL), double stranded DNA (dsDNA), endothelial cells (EC) and blood platelets was investigated. IgG fractions, reactive with these antigens, were isolated from the plasmas from 8 patients with systemic lupus erythematosus and tested for crossreactivity with anionic phospholipids (CL, phosphatidylserine, phosphatidylinositol), zwitterionic phospholipids (phosphatidylethanolamine, phosphatidylcholine), dsDNA, EC and platelets by enzyme-linked immunosorbent assays and for lupus anticoagulant (LAC) activity with a coagulation assay. Our results demonstrate the frequent occurrence of crossreactivity between antibodies to anionic phospholipids, EC and platelets. Crossreactivities between these antibodies and antibodies to dsDNA or zwitterionic phospholipids are exceptional. LAC activity was found in the anti-CL, anti-EC and anti-platelet fractions of only one patient. These findings support the hypothesis that subpopulations of antibodies directed against negatively charged phospholipids can bind to EC and blood platelets, which may have implications for the pathogenetic potential of antiphospholipid antibodies.

Antibody Specificity↗

PubMed1990

Silicic acid HPLC of cardiolipin, mono- and dilysocardiolipin, and several of their chemical derivatives.

A silicic acid HPLC system in hexane-2-propanol-1 mM H3PO4 50:50:3.5 (v/v/v) is described for the analysis and/or purification of cardiolipin (CL), monolysocardiolipin (MLCL), dilysocardiolipin (DLCL), and several of their chemical derivatives. Derivatives that have been successfully analyzed include CL that is acetylated, succinylated, or tetrahydropyranylated at the 2-hydroxyl; MLCL acetylated at the 2 and 2'-hydroxyls; DLCL acetylated at the 2-hydroxyl and both 2'-hydroxyls; and MLCL tetrahydropyranylated at only the 2-hydroxyl. Water can replace 1 mM H3PO4 in the eluting solvent, but prior conditioning of the silicic acid column with the phosphoric acid solvent is necessary for acceptable chromatography. The most significant factor affecting the elution times of these compounds is the percentage of aqueous component, i.e., water or 1 mM H3PO4.

Cardiolipins↗

PubMed1990

Determination of anti-cardiolipin and other antibodies in HIV-1-infected patients.

Anti-cardiolipin antibodies (ACA) were determined by an ELISA assay in 116 HIV-1-infected patients. A positive test was found in 27 patients (23.3%) with a predominance of IgG ACA isotype. No significant difference in ACA positivity was observed between homosexuals (22.2%) and intravenous drug users (25.8%). The presence of different immunological markers was compared in ACA-positive and ACA-negative patients: ACA-positive patients had higher IgG levels (p less than 0.05) and a tendency to higher frequencies of anti-ss DNA, anti-ds DNA, anti-i antibodies, as well as circulating immune complexes. When patients were classified according to CDC criteria, no significant difference was observed for the prevalence of ACA in class II (21.2%), in class III (25%), and in class IV (21%). Our results indicate that ACA antibodies occur with other immunological alterations in HIV-1-infected patients, but do not confirm that ACA is a useful prognostic marker for development of AIDS.

Adult↗

PubMed1989

Detection of anti-phospholipid (cardiolipin, phosphatidylserine) antibodies in the serum of patients with non insulin-dependent (type 2) diabetes mellitus and macroangiopathy. Coexistence of anti-platelet reactivity.

IgA and IgG antibodies against cardiolipin and/or phosphatidylserine were detected in the sera of patients with non insulin-dependent (type 2) diabetes mellitus. The highest prevalence was observed in particular in patients with macrovascular complications (86%). A significant increase of platelet bound IgA and IgG was observed also in patients with sera positive for anti-phospholipid antibodies suggesting the coexistence of reactivity against phospholipid and platelets. Several reports have focused on a new clinical entity characterized by the presence of anti-phospholipid and by a tendency to venous and arterial thrombosis. In addition to their acute thrombogenic effects, we suggest that anti-phospholipid antibodies may play a role in the impairment of the thromboresistant property of vascular endothelium and in the enhancement of platelet aggregation leading to the pathogenesis and/or progression of the macrovascular diabetic complications.

Aged↗

PubMed1987

Antibody-independent activation of C1. I. Differences in the mechanism of C1 activation by nonimmune activators and by immune complexes: C1r-independent activation of C1s by cardiolipin vesicles.

C1 activation is controlled by the regulatory protein C1-inhibitor (C1-INH). In contrast to immune-complex-induced activation, which is insensitive to C1-INH, antibody-independent activation of C1 is modulated by C1-INH. The mechanisms regulating nonimmune activation were studied with two phospholipids varying in their capacity to activate C1 in the presence of C1-INH: cardiolipin (CL) and phosphatidylglycerol (PG). Whereas C1-INH consistently suppressed activation by PG vesicles, a dose-dependent increase in C1 activation was measured with CL vesicles above 40 mole %. A similar dose-response binding of C1s requiring C1q, but not C1r, was detected only on CL vesicles, but neither on PG vesicles nor on immune complexes. This binding was Ca2+-dependent, suggesting that dimeric C1s is involved and was inhibited by spermine. The C1q-bound C1s was specifically cleaved at 37 degrees C into its active 58 kDa and 28 kDa chains, in the absence of C1r. On the addition of anti-CL antibodies, the C1q-mediated cleavage of C1s by CL vesicles was specifically inhibited. The cleavage of C1r on CL vesicles was also determined. When macromolecular C1 was offered in the presence of C1-INH, C1r cleavage was detected; however, the presence of C1s was a critical factor for C1r activation, because it was required on CL vesicles, but not on immune complexes. These results show that nonimmune activation of C1 presents specific features which distinguish it from immune complex-induced activation. These characteristics varied with the capacity of antibody-independent activators to activate C1 in the presence of C1-INH.

Antigen-Antibody Complex↗