Circulating heat shock protein 27 (HSPB1) levels in prediction of pre‐eclampsia: A pilot study

Martin, Raquel L.; Sottile, Mayra L.; Redondo, Analía Lourdes; Gómez, Laura Collados; Gauna, Gisel V.; Flamini, Marina Inés; Grajeda, Carina; Anzalone, Alfonsa C.; Rodríguez-Echandía, E. L.; Nadin, Silvina B.; Vargas–Roig, Laura M.

doi:10.1002/ijgo.13982

Cited by 5 publications

(6 citation statements)

References 24 publications

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“…To gain insights into the identified proteins’ dynamics during hypertensive vs normotensive pregnancies, we performed a systematic review of studies reporting observational associations of the prioritized proteins with HDPs. Forty-three studies met our inclusion criteria (eFigure 3 in Supplement 1), encompassing 9749 pregnant individuals with protein measurements who enrolled from 1998 to 2020 in their respective studies. Of those, 3122 individuals (32.0%) experienced an HDP, including 939 (9.6%) with gestational hypertension, 2167 (22.2%) with preeclampsia, and 16 (0.2%) without information on HDP subtype.…”

Section: Resultsmentioning

confidence: 99%

Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia

Schuermans,

Truong,

Ardissino

et al. 2024

JAMA Cardiol

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ImportanceHypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease.ObjectiveTo identify proteins in the circulation associated with HDPs.Design, Setting, and ParticipantsTwo-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease–related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins’ dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP–related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease–related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023.ExposuresGenetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs).Main Outcomes and MeasuresGestational hypertension and preeclampsia.ResultsGenetic association data for cardiovascular disease–related proteins were obtained from 21 758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393 238 female individuals (8636 cases and 384 602 controls) for gestational hypertension and 606 903 female individuals (16 032 cases and 590 871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro–brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP–related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins.Conclusions and RelevanceStudy findings suggest genetic associations of 4 cardiovascular disease–related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.

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Section: Resultsmentioning

confidence: 99%

Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia

Schuermans,

Truong,

Ardissino

et al. 2024

JAMA Cardiol

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“…(A) Tissue of human health, decidual cells are observed normal and arterioles without alterations. At 12‐weeks' gestation the cytotrophoblast secreted e Hsp‐27 55 and active production of anti‐inflammatory interleukin (IL)‐10 via intracellular p38MAPK pathways which reduce the secretion of proteins associated with oxidative stress, apoptosis, and the inflammatory response. 68 (B) However, this secretion profile changes in the development of preeclampsia.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Martin et al 55 showed that the e Hsp‐27 concentration increases up to twofold in the first and second trimesters in patients with PE compared with healthy term patients. Also, this was associated with a decrease in placental protein‐13, which is involved in normal placentation 56,57 .…”

Section: Discussionmentioning

confidence: 99%

First‐trimester plasma extracellular heat shock proteins levels and risk of preeclampsia

Robellada-Zárate

Luna-Palacios

Caballero

et al. 2023

J Cellular Molecular Medi

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Preeclampsia (PE) occurs annually in 8% of pregnancies. Patients without risk factors represent 10% of these. There are currently no first‐trimester biochemical markers that accurately predict PE. An increase in serum 60‐ and 70‐KDa extracellular heat shock proteins (eHsp) has been shown in patients who developed PE at 34 weeks. We sought to determine whether there is a relationship between first‐trimester eHsp and the development of PE. This was a prospective cohort study performed at a third level hospital in Mexico City from 2019 to 2020. eHsp levels were measured during the first‐trimester ultrasound in singleton pregnancies with no comorbidities. First‐trimester eHsp levels and biochemical parameters of organ dysfunction were compared between patients who developed preeclampsia and those who did not. All statistical analyses and model of correlation (r) between eHsp and clinical parameter were performed using bootstrapping R‐software. p‐values <0.05 were considered significant. The final analysis included 41 patients. PE occurred in 11 cases. eHsp‐60 and eHsp−70 were significantly higher at 12 weeks in patients who developed PE (p = 0.001), while eHsp‐27 was significantly lower (p = 0.004). Significant differences in first‐trimester eHsp concentration suggest that these are possible early biomarkers useful for the prediction of PE.

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“…34 The HSF1-HSPB1 pathway is well known for its role in maintaining cancer cell survival, 35 and HSPB1 has also been shown to be upregulated in preeclampsia. 36 However, their expression patterns and roles in EMS remain unclear. Our findings suggest that PTGES3, HSP90AA1, and HSPB1 are involved in the downstream mechanism of HSF1 in EMS, but further studies are warranted to validate their roles in EMS pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…HSP90AA1, a member of the HSP90 family, is a potential molecular target for cancer treatment 34 . The HSF1‐HSPB1 pathway is well known for its role in maintaining cancer cell survival, 35 and HSPB1 has also been shown to be upregulated in preeclampsia 36 . However, their expression patterns and roles in EMS remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Serum HSF1 is upregulated in endometriosis patients and serves as a potential diagnostic biomarker

Pan

Wan

2023

The Kaohsiung J of Med Scie

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Endometriosis (EMS) is a prevalent gynecological condition lacking reliable diagnostic biomarkers. This prospective study aimed to analyze the potential of serum heat shock transcription factor 1 (HSF1) as a diagnostic marker for EMS. Clinical features of 92 EMS patients and 52 controls were recorded, revealing significant differences in dysmenorrhea, dyspareunia, pelvic pain, nulliparity, and CA125 levels. Serum HSF1 was upregulated in EMS patients, with higher levels in American Society for Reproductive Medicine (ASRM) III/IV than ASRM I/II. Receiver operating characteristic curve analysis demonstrated good diagnostic function for serum HSF1 (AUC: 0.857, sensitivity: 91.30%, specificity: 63.46%). Serum HSF1, dysmenorrhea, dyspareunia, and nulliparity were independent risk factors for EMS, while dysmenorrhea and serum HSF1 were independent risk factors for EMS severity. Additionally, the GSE25628 dataset was downloaded from the GEO database for differential analysis of gene expression. The HSF1 downstream target genes PTGES3, HSP90AA1, and HSPB1 showed significant differential expression in EMS, suggesting their involvement in the regulatory mechanism of HSF1 in EMS.

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Circulating heat shock protein 27 (HSPB1) levels in prediction of pre‐eclampsia: A pilot study

Cited by 5 publications

References 24 publications

Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia

Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia

First‐trimester plasma extracellular heat shock proteins levels and risk of preeclampsia

Serum HSF1 is upregulated in endometriosis patients and serves as a potential diagnostic biomarker

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