Differentiation of HELLP patients from healthy pregnant women by proteome analysis—On the way towards a clinical marker set☆

Heitner, J C; Koy, Cornelia; Kreutzer, Michael; Gerber, Bernd; Reimer, Toralf; Glocker, Michael O.

doi:10.1016/j.jchromb.2006.06.002

Cited by 36 publications

(32 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…All of the above-mentioned pathways are reported to contribute to the pathogenesis of preeclampsia (45). Circulating levels of total fibrinogen increase 2-fold during the course of a healthy pregnancy (46) and are significantly increased in preeclampsia (7,47), providing a link with the hypercoagulable states of pregnancy and with preeclampsia in particular. Moreover, increased fibrinogen levels have been linked to an increased risk of coronary artery disease (48).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

An altered pattern of circulating apolipoprotein E3 isoforms is implicated in preeclampsia

Atkinson

Blumenstein

Black³

et al. 2009

Journal of Lipid Research

View full text Add to dashboard Cite

Preeclampsia is a common pregnancy complication that is an important cause of preterm birth and fetal growth restriction. Because there is no diagnostic test yet available for preeclampsia, we used a proteomic approach to identify novel serum/plasma biomarkers for this condition. We conducted case control studies comparing nulliparous women who developed preeclampsia at 36-38 weeks of gestation with healthy nulliparous women matched by gestational age at sampling. Serum/plasma was depleted of six abundant proteins and analyzed by two-dimensional gel electrophoresis (n 5 12 per group) and difference gel electrophoresis (n 5 12 per group). Differences in abundance of protein spots were detected by univariate and multivariate statistical analyses. Proteins were identified by mass spectrometry and expression of selected proteins was validated by immunoblotting. Proteins whose concentrations were selectively associated with preeclampsia included apolipoprotein E (apoE), apoC-II, complement factor C3c, fibrinogen, transthyretin, and complement factor H-related protein 2. An increase in a deglycosylated isoform of apoE3 and concomitantly decreased amounts of one apoE3 glycoisoform were identified in preeclamptic plasma and confirmed by immunoblotting. Altered production of these preeclampsia-related apoE3 isoforms might impair reverse cholesterol transport, contributing to arterial damage. These findings point to a novel mechanistic link between preeclampsia and subsequent cardiovascular disease.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Recently, two-dimensional gel electrophoresis (2DE) proteomic techniques have been used to investigate changes in the plasma proteome in preeclampsia (6,7). A 2DE study of HELLP syndrome, a severe form of preeclampsia, identified one downregulated and five upregulated plasma proteins (7).…”

mentioning

confidence: 99%

An altered pattern of circulating apolipoprotein E3 isoforms is implicated in preeclampsia

Atkinson

Blumenstein

Black³

et al. 2009

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…Its major complications are eclampsia and HELLP syndrome, both of which are potential life-threatening events. Eclampsia is characterized by grand mal-like seizures, whereas HELLP syndrome manifests itself with hemolysis, elevated liver enzymes, and low platelet counts [3]. Furthermore, the underlying condition has the potential to affect the fetus, as about 25% of babies born to women with preeclampsia are small for gestational age (SGA).…”

mentioning

confidence: 99%

“…Matrixassisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is an automated technique that can detect hundreds of peptide and/or protein ion signals from clinically obtained body fluids in one measurement with good reproducibility and robustness. Hence, MALDI-TOF MS has enabled the multiparametric analysis of the reservoir of proteins derived from high-abundance endogenous circulating molecules from pregnant women [3,17]. As a consequence, mass spectrometric measurements of the entire set of protein abundances in biological fluids (proteome signatures) allow the representation of a particular pathology, and the resulting signature is in the best case unique to the disease.…”

mentioning

confidence: 99%

Multifactorial analysis of affinity-mass spectrometry data from serum protein samples: A strategy to distinguish patients with preeclampsia from matching control individuals

Pecks

Seidenspinner

Röwer

et al. 2010

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

A multifactorial differential analysis of serum proteins using mass spectrometry distinguished samples from pregnant women with severe early-onset preeclampsia (n ϭ 11) from those of control individuals with uneventful pregnancies (n ϭ 13). Serum proteins were fractionated by either their affinities to reversed-phase material coated magnetic beads or by fractionated precipitation. The on-average most abundant ion signals were observed at m/z 9390, 9103, and 8886. The best differentiating ion signals between the two sample groups were found at m/z 13,715, 13,834, and 13,891. The normalized intensities of these ion signals were on-average lower in the preeclampsia group than in the control group. The six ion signal intensities enabled sorting of the individual spectra with high accuracy. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed that a protein band migrating just above the 14 kDa marker band contained transthyretin (P02766; M r (avg.): 13,761). Densitometric analysis of the transthyretin bands showed lower intensities in the preeclampsia samples with respect to those of the controls. Nephelometric analysis of the serum samples determined the mean concentration of transthyretin in the preeclampsia group were lower (0.16 mg/mL; range: 0.13 to 0.20; SD: 0.03) than that in the control group (0.19 mg/mL; range: 0.14 to 0.22; SD: 0.02), substantiating the role of transthyretin concentration differences in the comparison of the two groups. Altogether, our findings support the theory of preeclampsia being a heterogeneous disorder that might be sub-classified by a defined proteome signature in maternal blood using multifactorial analysis of affinity-fractionated serum samples. (J Am

show abstract

“…Ayr›ca preeklmepside, fibronektin düzeyindeki bir art›fl damarsal bir tutulumu gösterir. ‹kinci trimestirde, yüksek alfa fetoprotein (AFP) ve human korionik gonadotropin (hCG) de¤erleri, HELLP sendromu riskini 47 kat artt›r›r (15) . Karaci¤erde subkapsüler veya parankim içi hematom ve karaci¤er rüptürü olan hamileler için, iyonize radyasyon vermeyen ultrasonografi (USG) ve Magnetik rezonans (MR) tercih edilir.…”

Section: Patogenezunclassified

HELLP Sendromunda Acil Yaklaşım

Baştürk¹

2009

jaem

View full text Add to dashboard Cite

HELLP syndrome (haemolysis, elevated liver enzymes, low platelet count) is a multisystemic disorder that has a poor prognosis and occurring usually in older multiparous women in the third trimester of pregnancy due to a generalized microangiopathy. If patient has complications such as hepatic rupture, cerebral hemorrhage and disseminated intravascular coagulation (DIC), materno-fetal mortality is high. Severe thrombocytopenia worsens prognosis. The early recognition of HELLP syndrome and the rapid initiation of therapy are required for the improvement of materno-fetal prognosis. The only specific therapy in HELLP syndrome is induction of delivery.ÖZET HELLP sendromu (Hemoliz, karaci¤er enzimlerinde yükselme ve plateletlerde azalma), yayg›n mikroanjiopatilere ba¤l› olarak genellikle multipar bayanlar›n üçüncü trimestirinde ortaya ç›kan kötü prognozlu multisistemik bir hastal›kt›r. E¤er hastada, karaci¤er rüptürü, beyin kanamas› ve yayg›n damar içi p›ht›laflmas› (D‹C) varsa, anne-bebek mortalitesi yüksektir. Ciddi trombositopeni prognozu kötülefltirir. HELLP tablosunun erken tan›nmas› ve tedavinin h›zl› bafllanmas›, anne-bebek prognozunun düzeltilmesi için gereklidir. HELLP tablosunun özellikli tedavisi, do¤um eyleminin gerçeklefltirilmesidir.

show abstract

Differentiation of HELLP patients from healthy pregnant women by proteome analysis—On the way towards a clinical marker set☆

Cited by 36 publications

References 32 publications

An altered pattern of circulating apolipoprotein E3 isoforms is implicated in preeclampsia

An altered pattern of circulating apolipoprotein E3 isoforms is implicated in preeclampsia

Multifactorial analysis of affinity-mass spectrometry data from serum protein samples: A strategy to distinguish patients with preeclampsia from matching control individuals

HELLP Sendromunda Acil Yaklaşım

Contact Info

Product

Resources

About