BBA clinical最新文献

{"title":"Cumulus cell mitochondrial activity in relation to body mass index in women undergoing assisted reproductive therapy","authors":"Victoria K. Gorshinova ,&nbsp;Daria V. Tsvirkun ,&nbsp;Iuliia A. Sukhanova ,&nbsp;Nadezhda V. Tarasova ,&nbsp;Maria A. Volodina ,&nbsp;Maria V. Marey ,&nbsp;Veronika U. Smolnikova ,&nbsp;Mikhail Yu. Vysokikh ,&nbsp;Gennady T. Sukhikh","doi":"10.1016/j.bbacli.2017.03.005","DOIUrl":"10.1016/j.bbacli.2017.03.005","url":null,"abstract":"<div><p>Most studies have considered the negative influence of obesity on fertility in both genders. In the present study, we assessed mitochondrial activity expressed as the mitochondrial potential index (MPI) in cumulus cells from obese women and women with a normal body mass index (BMI) during assisted reproductive therapy. The results revealed a significant reduction of MPI with increased body mass. The lower MPI levels in cumulus cells from obese women may reflect mitochondrial dysfunction caused by oxidative stress, which can affect the cumulus-oocyte complex and have an impact on oocyte development.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2017.03.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35129741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signaling mechanisms implicated in cranial sutures pathophysiology: Craniosynostosis","authors":"Maria A. Katsianou ,&nbsp;Christos Adamopoulos ,&nbsp;Heleni Vastardis ,&nbsp;Efthimia K. Basdra","doi":"10.1016/j.bbacli.2016.04.006","DOIUrl":"10.1016/j.bbacli.2016.04.006","url":null,"abstract":"<div><p>Normal extension and skull expansion is a synchronized process that prevails along the osteogenic intersections of the cranial sutures. Cranial sutures operate as bone growth sites allowing swift bone generation at the edges of the bone fronts while they remain patent. Premature fusion of one or more cranial sutures can trigger craniosynostosis, a birth defect characterized by dramatic manifestations in appearance and functional impairment. Up until today, surgical correction is the only restorative measure for craniosynostosis associated with considerable mortality. Clinical studies have identified several genes implicated in the pathogenesis of craniosynostosis syndromes with useful insights into the underlying molecular signaling events that determine suture fate. In this review, we exploit the intracellular signal transduction pathways implicated in suture pathobiology, in an attempt to identify key signaling molecules for therapeutic targeting.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.04.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54180857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction","authors":"Poonam Verma ,&nbsp;Alpana Singh ,&nbsp;Dominic Ngima Nthenge-Ngumbau ,&nbsp;Usha Rajamma ,&nbsp;Swagata Sinha ,&nbsp;Kanchan Mukhopadhyay ,&nbsp;Kochupurackal P Mohanakumar","doi":"10.1016/j.bbacli.2016.10.003","DOIUrl":"10.1016/j.bbacli.2016.10.003","url":null,"abstract":"<div><h3>Background</h3><p>Pathophysiology of attention-deficit hyperactivity disorder (ADHD) is not known, and therefore the present study investigated mitochondrial defects, if any in cybrids created from patients and control population.</p></div><div><h3>Methods</h3><p>To investigate mitochondrial pathology in ADHD, cybrids cell lines were created from ADHD probands and controls by fusing their platelets with ρ⁰-cells prepared from SH-SY5Y neuroblastoma cell line. Cellular respiration, oxidative stress, mitochondrial membrane potential and morphology were evaluated employing oxygraph, mitochondria-specific fluorescence staining and evaluation by FACS, and immunocytochemistry. HPLC-electrochemical detection, quantitative RT-PCR and Blue Native PAGE were employed respectively for assays of serotonin, mitochondrial ATPase 6/8 subunits levels and complex V activity.</p></div><div><h3>Results</h3><p>Significantly low cellular and mitochondrial respiration, ATPase6/8 transcripts levels, mitochondrial complex V activity and loss of mitochondrial membrane potential and elevated oxidative stress were observed in ADHD cybrids. Expression of monoamine oxidizing mitochondrial enzymes, MAO-A and MAO-B levels remained unaffected. Two-fold increase in serotonin level was noted in differentiated cybrid-neurons.</p></div><div><h3>Conclusions</h3><p>Since cybrids are shown to replicate mitochondrial defects seen in post-mortem brains, these observed defects in ADHD cybrids strongly suggest mitochondrial pathology in this disorder.</p></div><div><h3>General significance</h3><p>Mitochondrial defects are detected in ADHD cybrids created from patients' platelets, implying bioenergetics crisis in the mitochondria could be a contributory factor for ADHD pathology and/or phenotypes.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.10.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54181399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The broken “Off” switch in cancer signaling: PP2A as a regulator of tumorigenesis, drug resistance, and immune surveillance","authors":"Peter P. Ruvolo","doi":"10.1016/j.bbacli.2016.08.002","DOIUrl":"10.1016/j.bbacli.2016.08.002","url":null,"abstract":"<div><p>Aberrant activation of signal transduction pathways can transform a normal cell to a malignant one and can impart survival properties that render cancer cells resistant to therapy. A diverse set of cascades have been implicated in various cancers including those mediated by serine/threonine kinases such RAS, PI3K/AKT, and PKC. Signal transduction is a dynamic process involving both “On” and “Off” switches. Activating mutations of RAS or PI3K can be viewed as the switch being stuck in the “On” position resulting in continued signaling by a survival and/or proliferation pathway. On the other hand, inactivation of protein phosphatases such as the PP2A family can be seen as the defective “Off” switch that similarly can activate these pathways. A problem for therapeutic targeting of PP2A is that the enzyme is a hetero-trimer and thus drug targeting involves complex structures. More importantly, since PP2A isoforms generally act as tumor suppressors one would want to activate these enzymes rather than suppress them. The elucidation of the role of cellular inhibitors like SET and CIP2A in cancer suggests that targeting these proteins can have therapeutic efficacy by mechanisms involving PP2A activation. Furthermore, drugs such as FTY-720 can activate PP2A isoforms directly. This review will cover the current state of knowledge of PP2A role as a tumor suppressor in cancer cells and as a mediator of processes that can impact drug resistance and immune surveillance.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.08.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34677212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of reactive oxygen species in the anterior eye segment. Synergistic codrugs of N-acetylcarnosine lubricant eye drops and mitochondria-targeted antioxidant act as a powerful therapeutic platform for the treatment of cataracts and primary open-angle glaucoma","authors":"Mark A. Babizhayev","doi":"10.1016/j.bbacli.2016.04.004","DOIUrl":"10.1016/j.bbacli.2016.04.004","url":null,"abstract":"<div><p>Senile cataract is a clouding of the lens in the aging eye leading to a decrease in vision. Symptoms may include faded colors, blurry vision, halos around light, trouble with bright lights, and trouble seeing at night. This may result in trouble driving, reading, or recognizing faces. Cataracts are the cause of half of blindness and 33% of visual impairment worldwide. Cataracts result from the deposition of aggregated proteins in the eye lens and lens fiber cells plasma membrane damage which causes clouding of the lens, light scattering, and obstruction of vision. ROS induced damage in the lens cell may consist of oxidation of proteins, DNA damage and/or lipid peroxidation, all of which have been implicated in cataractogenesis. The inner eye pressure (also called intraocular pressure or IOP) rises because the correct amount of fluid can't drain out of the eye. With primary open-angle glaucoma, the entrances to the drainage canals are clear and should be working correctly. The clogging problem occurs further inside the drainage canals, similar to a clogged pipe below the drain in a sink.</p><p>The excessive oxidative damage is a major factor of the ocular diseases because the mitochondrial respiratory chain in mitochondria of the vital cells is a significant source of the damaging reactive oxygen species superoxide and hydrogen peroxide. However, despite the clinical importance of mitochondrial oxidative damage, antioxidants have been of limited therapeutic success. This may be because the antioxidants are not selectively taken up by mitochondria, but instead are dispersed throughout the body, ocular tissues and fluids' moieties.</p><p>This work is an attempt to integrate how mitochondrial reactive oxygen species (ROS) are altered in the aging eye, along with those protective and repair therapeutic systems believed to regulate ROS levels in ocular tissues and how damage to these systems contributes to age-onset eye disease and cataract formation.</p><p>Mitochondria-targeted antioxidants might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner mitochondrial membrane in vivo. The authors developed and patented the new ophthalmic compositions including N-acetylcarnosine acting as a prodrug of naturally targeted to mitochondria <span>l</span>-carnosine endowed with pluripotent antioxidant activities, combined with mitochondria-targeted rechargeable antioxidant (either MitoVit E, Mito Q or SkQs) as a potent medicine to treat ocular diseases. Such specificity is explained by the fact that developed compositions might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner mitochondrial membrane in vivo and outside mitochondria in the cellular and tissue structures of the lens and eye compartments.</p><p>Mitochondrial targeting of compounds with universal types of antioxidant activity represents a promising approach for treating a number of ROS-related ocular diseases of the a","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.04.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34668434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ST-elevation myocardial infarction risk in the very elderly","authors":"Alessandra M. Campos PhD ,&nbsp;Andrea Placido-Sposito MSc ,&nbsp;Wladimir M. Freitas MD MSc ,&nbsp;Filipe A. Moura MD ,&nbsp;Maria Elena Guariento MD PhD ,&nbsp;Wilson Nadruz Junior MD PhD ,&nbsp;Emilio H. Moriguchi MD PhD ,&nbsp;Andrei C. Sposito MD PhD ,&nbsp;on behalf of Brasilia Study on Healthy Aging and Brasilia Heart Study","doi":"10.1016/j.bbacli.2016.09.001","DOIUrl":"10.1016/j.bbacli.2016.09.001","url":null,"abstract":"<div><h3>Background</h3><p>Despite the high incidence and mortality of ST-segment elevation myocardial infarction (STEMI) among the very elderly, risk markers for this condition remain poorly defined. This study was designed to identify independent markers of STEMI among individuals carefully selected for being healthy or manifesting STEMI in &lt;<!--> <!-->24<!--> <!-->h.</p></div><div><h3>Methods</h3><p>We enrolled participants aged 80<!--> <!-->years or older of whom 50 were STEMI patients and 207 had never manifested cardiovascular diseases. Blood tests, medical and psychological evaluations were obtained at study admission. Odds Ratio (OR) and attributed risk (AR) were obtained by multivariate regression models using STEMI as dependent variable.</p></div><div><h3>Results</h3><p>Low glomerular filtration rate (GFR) [OR:4.41 (1.78–10.95); <em>p</em> <!-->=<!--> <!-->0.001], reduced levels of HDL-C [OR:10.70 (3.88–29.46); <em>p</em> <!-->=<!--> <!-->0.001], male gender [OR:12.08 (5.82–25.08); p<!--> <!-->=<!--> <!-->0.001], moderate to severe depressive symptoms [OR:10.00 (2.82–35.50); p<!--> <!-->=<!--> <!-->0.001], prior smoking [OR:2.00 (1.05–3.80); <em>p</em> <!-->=<!--> <!-->0.034] and current smoking [OR:6.58 (1.99–21.70); <em>p</em> <!-->=<!--> <!-->0.002] were significantly associated with STEMI. No association was found between STEMI and age, diabetes, hypertension, mild depressive symptoms, triglyceride or LDL-C.</p></div><div><h3>Conclusions</h3><p>This is the first case–control study carried out with very elderlies to assess STEMI risk. Our findings indicate that reduced HDL-C, GFR, male gender, smoking habits and moderate to severe depressive symptoms are markers of STEMI in this age group.</p></div><div><h3>General Significance</h3><p>In Individuals aged 80 or more years, a greater attention must be paid to low HDL-C and GFR at the expense of conventional STEMI risk factors for younger adults such as diabetes mellitus, hypertension and high LDL-C or triglyceride.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.09.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54181470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetics in heart failure phenotypes","authors":"Alexander Berezin","doi":"10.1016/j.bbacli.2016.05.005","DOIUrl":"10.1016/j.bbacli.2016.05.005","url":null,"abstract":"<div><p>Chronic heart failure (HF) is a leading clinical and public problem posing a higher risk of morbidity and mortality in different populations. HF appears to be in both phenotypic forms: HF with reduced left ventricular ejection fraction (HFrEF) and HF with preserved left ventricular ejection fraction (HFpEF). Although both HF phenotypes can be distinguished through clinical features, co-morbidity status, prediction score, and treatment, the clinical outcomes in patients with HFrEF and HFpEF are similar. In this context, investigation of various molecular and cellular mechanisms leading to the development and progression of both HF phenotypes is very important. There is emerging evidence that epigenetic regulation may have a clue in the pathogenesis of HF. This review represents current available evidence regarding the implication of epigenetic modifications in the development of different HF phenotypes and perspectives of epigenetic-based therapies of HF.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.05.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34494002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment with recombinant human bone morphogenetic protein 7 leads to a transient induction of neutralizing autoantibodies in a subset of patients","authors":"Andrea Schuette ,&nbsp;Arash Moghaddam ,&nbsp;Petra Seemann ,&nbsp;Georg N. Duda ,&nbsp;Gerhard Schmidmaier ,&nbsp;Lutz Schomburg","doi":"10.1016/j.bbacli.2016.08.001","DOIUrl":"10.1016/j.bbacli.2016.08.001","url":null,"abstract":"<div><h3>Background</h3><p>Recombinant human bone morphogenetic protein 7 (rhBMP7) is applied for treatment of bone fractures, especially tibial non-unions. Its application may induce autoantibodies (aAB) affecting the targeted and endogenous signaling pathways and in turn negatively impact treatment efficacy.</p></div><div><h3>Methods</h3><p>Novel and sensitive assays for the quantification of BMP7-aAB and BMP2-aAB were established and used to analyze serum samples from healthy controls (n<!--> <!-->=<!--> <!-->100 men, n<!--> <!-->=<!--> <!-->100 women) and patients with long bone fracture (n<!--> <!-->=<!--> <!-->265) treated or not with rhBMP7. Sera from three to nine time points per patient were available and enabled the evaluation of aAB over a time course of up to one year. Functional activity of the BMP-aAB was tested with a BMP-responsive cell-based reporter assay. Consolidation of the fracture was evaluated as clinical outcome potentially affected by BMP7-aAB.</p></div><div><h3>Results</h3><p>Prevalence of BMP7-aAB and BMP2-aAB was 1–2.5% in non-treated patients or healthy controls. The rhBMP7 treatment induced a transient increase in BMP7-aAB in a subset of patients, returning to non-detectable levels within six months. IgG from BMP7-aAB positive sera inhibited dose dependently the BMP7-reporter gene activity, whereas control sera were without effect. Successful consolidation of the fracture was observed in the majority of both aAB-positive and aAB-negative patients.</p></div><div><h3>General significance</h3><p>We conclude that BMP7-aAB can be detected as natural aAB in healthy subjects, and are transiently induced by rhBMP7 therapy in a subset of patients. The aAB are capable of antagonizing BMP7 signaling in vitro, but do not preclude treatment success in patients.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.08.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54180972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apoptotic and stress signaling markers are augmented in preeclamptic placenta and umbilical cord","authors":"Syeda H. Afroze ,&nbsp;Ram R. Kalagiri ,&nbsp;Michelle Reyes ,&nbsp;Jacqueline D. Zimmerman ,&nbsp;Madhava R. Beeram ,&nbsp;Nathan Drever ,&nbsp;David C. Zawieja ,&nbsp;Thomas J. Kuehl ,&nbsp;Mohammad N. Uddin","doi":"10.1016/j.bbacli.2016.05.003","DOIUrl":"10.1016/j.bbacli.2016.05.003","url":null,"abstract":"<div><h3>Objective</h3><p>Preeclampsia (preE) has a significant link to alterations of placental function leading to stress and apoptotic signaling, which pass the placental barrier and leave persistent defect in the circulation of the offspring. We assessed apoptotic signaling in placentas and umbilical cords from patients with and without preE.</p></div><div><h3>Methods</h3><p>We collected placental and cord tissues from 27 normal pregnant (NP) women and 20 preE consenting patients after delivery in an IRB approved prospective study. p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, pro-apoptotic Bcl-2-associated X (Bax), anti-apoptotic Bcl-2, caspase-9, and pro-inflammatory cyclooxygenase-2 (Cox-2) were evaluated by western blot and immunohistochemistry. Comparisons were performed using Student's <em>t</em>-test.</p></div><div><h3>Results</h3><p>p38 phosphorylation (Placenta: 1.5 fold, Cord: 1.7 fold), ratio of Bax/Bcl-2 (Placenta: 1.7 fold, Cord: 2.2 fold), caspase-9 (Placenta: 1.5 fold, Cord: 1.8 fold) and Cox-2 (Placenta: 2.5 fold, Cord: 2.3 fold) were up-regulated (p<!--> <!-->&lt;<!--> <!-->0.05) in preE compared to NP patients. Average hospital stays for preE babies were longer than NP babies. No complications were reported for NP babies; however, all of preE babies had multiple complications.</p></div><div><h3>Conclusions</h3><p>Apoptotic and stress signaling are augmented in preE placenta and cord tissue that alter the intrauterine environment and activates the detrimental signaling that is transported to fetus.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.05.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34604852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid profile of platelets and platelet-derived microparticles in ovarian cancer","authors":"Qianghua Hu ,&nbsp;Miao Wang ,&nbsp;Min Soon Cho ,&nbsp;Chunyan Wang ,&nbsp;Alpa M. Nick ,&nbsp;Perumal Thiagarajan ,&nbsp;Fleur M. Aung ,&nbsp;Xianlin Han ,&nbsp;Anil K. Sood ,&nbsp;Vahid Afshar-Kharghan","doi":"10.1016/j.bbacli.2016.06.003","DOIUrl":"10.1016/j.bbacli.2016.06.003","url":null,"abstract":"<div><h3>Background</h3><p>Ovarian cancer patients have a high risk of developing venous thrombosis. The membrane lipid bilayer of platelets and platelet-derived microparticles (PMP) provides a platform for assembly of coagulation proteins and generation of blood clots.</p></div><div><h3>Methods</h3><p>We compared the lipid composition of platelets and PMPs in patients with ovarian cancer to those in healthy subjects. We used shotgun lipidomics to quantify 12 classes and 177 species of lipids.</p></div><div><h3>Results</h3><p>We found a significant change in 2 classes of lipids in platelets and PMPs isolated from ovarian cancer patients: higher phosphatidylinositol and lower lyso-phosphatidylcholine. The level of 28 species of lipids was also significantly altered in the direction of an increase in the pro-coagulant and a reduction in the anticoagulant lipids. We found that cancer platelets expressed less lipid phosphate phosphatase 1 (LPP1), a key enzyme in phospholipid biosynthesis pathways, than normal platelets. The reduction in LPP1 might contribute to the changes in the lipid profile of cancer platelets.</p></div><div><h3>Conclusion</h3><p>Our results support a procoagulant lipid profile of platelets in ovarian cancer patients that can play a role in the increased risk of venous thrombosis in these patients.</p></div><div><h3>General significance</h3><p>As far as we are aware, our study is the first study on platelet lipidomics in ovarian cancer. The importance of our findings for the future studies are: 1) a similar change in lipid profile of platelets and PMP may be responsible for hypercoagulability in other cancers, and 2) plasma level of high-risk lipids for venous thrombosis may be useful biomarkers.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.06.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34699792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}