Preeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes and symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, a comprehensive understanding of the immune microenvironment in the placenta of PE and the differences between PE and GDM is still lacking. In this study, cytometry by time of flight indicated that the frequencies of memory-like Th17 cells (CD45RA⁻CCR7⁺IL-17A⁺CD4⁺), memory-like CD8⁺ T cells (CD38⁺CXCR3⁻CCR7⁺Helios⁻CD127⁻CD8⁺) and pro-inflam Macs (CD206⁻CD163⁻CD38^midCD107a^lowCD86^midHLA-DR^midCD14⁺) were increased, while the frequencies of anti-inflam Macs (CD206⁺CD163⁻CD86^midCD33⁺HLA-DR⁺CD14⁺) and granulocyte myeloid-derived suppressor cells (gMDSCs, CD11b⁺CD15^hiHLA-DR^low) were decreased in the placenta of PE compared with that of normal pregnancy (NP), but not in that of GDM or GDM&PE. The pro-inflam Macs were positively correlated with memory-like Th17 cells and memory-like CD8⁺ T cells but negatively correlated with gMDSCs. Single-cell RNA sequencing revealed that transferring the F4/80⁺CD206⁻ pro-inflam Macs with a Folr2⁺Ccl7⁺Ccl8⁺C1qa⁺C1qb⁺C1qc⁺ phenotype from the uterus of PE mice to normal pregnant mice induced the production of memory-like IL-17a⁺Rora⁺Il1r1⁺TNF⁺Cxcr6⁺S100a4⁺CD44⁺ Th17 cells via IGF1–IGF1R, which contributed to the development and recurrence of PE. Pro-inflam Macs also induced the production of memory-like CD8⁺ T cells but inhibited the production of Ly6g⁺S100a8⁺S100a9⁺Retnlg⁺Wfdc21⁺ gMDSCs at the maternal–fetal interface, leading to PE-like symptoms in mice. In conclusion, this study revealed the PE-specific immune cell network, which was regulated by pro-inflam Macs, providing new ideas about the pathogenesis of PE.

Background: Several fields have described low reproducibility of scientific research and poor accessibility in research reporting practices. Although previous reports have investigated accessible reporting practices that lead to reproducible research in other fields, to date, no study has explored the extent of accessible and reproducible research practices in cardiovascular science literature.

Methods: To study accessibility and reproducibility in cardiovascular research reporting, we screened 639 randomly selected articles published in 2019 in three top cardiovascular science publications: Circulation, the European Heart Journal, and the Journal of the American College of Cardiology (JACC). Of those 639 articles, 393 were empirical research articles. We screened each paper for accessible and reproducible research practices using a set of accessibility criteria including protocol, materials, data, and analysis script availability, as well as accessibility of the publication itself. We also quantified the consistency of open research practices within and across cardiovascular study types and journal formats.

Results: We identified that fewer than 2% of cardiovascular research publications provide sufficient resources (materials, methods, data, and analysis scripts) to fully reproduce their studies. Of the 639 articles screened, 393 were empirical research studies for which reproducibility could be assessed using our protocol, as opposed to commentaries or reviews. After calculating an accessibility score as a measure of the extent to which an article makes its resources available, we also showed that the level of accessibility varies across study types with a score of 0.08 for Case Studies or Case Series and 0.39 for Clinical Trials (p = 5.500E-5) and across journals (0.19 through 0.34, p = 1.230E-2). We further showed that there are significant differences in which study types share which resources.

Conclusion: Although the degree to which reproducible reporting practices are present in publications varies significantly across journals and study types, current cardiovascular science reports frequently do not provide sufficient materials, protocols, data, or analysis information to reproduce a study. In the future, having higher standards of accessibility mandated by either journals or funding bodies will help increase the reproducibility of cardiovascular research.

Funding: Authors Gabriel Heckerman, Arely Campos-Melendez, and Chisomaga Ekwueme were supported by an NIH R25 grant from the National Heart, Lung and Blood Institute (R25HL147666). Eileen Tzng was supported by an AHA Institutional Training Award fellowship (18UFEL33960207).