Human SPON1 blocking peptide

The anti-implantation effects of high oestradiol (E-2) concentrations could be mediated by E-2 metabolites. Herein, we examined whether 2-methoxyoestradiol (2ME) impairs embryo implantation via its target protein F-spondin. Mice on Day 3 of pregnancy were treated with E-2 concomitantly with the cathecol-O-methyl transferase inhibitor OR486 and the number of implanted embryos was recorded 5 days later. The effect of 2ME or 4-methoxyoestradiol (4ME) on embryo implantation was also investigated. Plasma and uterine levels of 2ME were measured 0.5, 1 or 3h after E-2 treatment while the mRNA for spondin 1 (Spon1) and F-spondin were determined in the uterus 3, 6, 12 or 24h after 2ME treatment. Finally, the effect of a neutralising F-spondin antibody on the anti-implantation effect of 2ME was explored. OR486 blocked the anti-implantation effect of E-2; 2ME, but not 4ME, affected embryo implantation. The 2ME concentration was increased after 0.5 and 1h in plasma and 3h in uterine fluid following E-2 treatment. 2ME increased levels of Spon1 at 12 and 24h although F-spondin was increased at 12h. F-spondin antibody blocked the effect of 2ME on embryo implantation. We conclude that 2ME impairs mouse embryo implantation via activation of F-spondin in the uterus.

Aims To identify novel risk markers for incident heart failure using proteomic profiling of 80 proteins previously associated with cardiovascular pathology. Methods and results Proteomic profiling (proximity extension assay) was performed in two community-based prospective cohorts of elderly individuals without heart failure at baseline: the Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS, n = 901, median age 70.2 (interquartile range 70.0-70.3) years, 80 events]; and the Uppsala Longitudinal Study of Adult Men [ULSAM, n= 685, median age 77.8 (interquartile range 76.9-78.1) years, 90 events]. Twenty-nine proteins were associated with incident heart failure in the discovery cohort PIVUS after adjustment for age and sex, and correction for multiple testing. Eighteen associations replicated in ULSAM. In pooled analysis of both cohorts, higher levels of nine proteins were associated with incident heart failure after adjustment for established risk factors: growth differentiation factor 15 (GDF-15), T-cell immunoglobulin and mucin domain 1 (TIM-1), tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), spondin-1 (SPON1), matrix metalloproteinase-12 (MMP-12), follistatin (FS), urokinase-type plasminogen activator surface receptor (U-PAR), osteoprotegerin (OPG), and suppression of tumorigenicity 2 (ST2). Of these, GDF-15, U-PAR, MMP-12, TRAIL-R2, SPON1 and FS were associated with worsened echocardiographic left ventricular systolic function at baseline, while only TIM-1 was positively associated with worsened diastolic function (P < 0.02 for all). Conclusion Proteomic profiling identified several novel associations between proteins involved in apoptosis, inflammation, matrix remodelling, and fibrinolysis with incident heart failure in elderly individuals. Our results encourage additional studies investigating the underlying mechanisms and the clinical utility of our findings.