Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) protein is one of the factors associated with oxidative stress and dyslipidemia disorders. Objective: This study aimed to evaluate the lipid profile, PCSK9 levels, and oxidative stress in preeclampsia. Materials and Methods: This case-control study was conducted at Sina hospital in Hamadan University of Medical Sciences, Hamadan, Iran from August 2020-May 2021. The average maternal age of included participants was 30 yr with 30 preeclampsia and 30 healthy pregnant women. After clinical examination, the fasting blood samples were collected, and the serum PCSK9 protein concentration, superoxide dismutase, glutathione peroxidase activities, and glutathione levels were determined by enzyme-linked immunosorbent assay. Total antioxidant capacity, total oxidant status, and malondialdehyde levels were determined manually. Results: The average maternal age of participants were 29. 97 ± 4. 75 and 31. 23 ± 5. 85 yr, respectively. The concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), PCSK9, total antioxidant capacity, and malondialdehyde levels were higher in the preeclampsia group compared with control (p < 0. 02). Total oxidant status, glutathione levels, superoxide dismutase, glutathione peroxidase activities were lower in the cases group compared with the control group (p < 0. 01). The PCSK9 variable had a significant negative association with antioxidant parameters,however, a significant positive association was observed between PCSK9 level and parameters of LDL-C. Conclusion: PCSK9 is associated with increased serum levels of LDL-C and oxidative factors in pregnant women that increase the risk of endothelial damage and hypertension in preeclampsia.

Furin is a Ca2+ -dependent serine protease which cleaves proprotein substrates at the Arg-Xaa-(Lys/Arg)-Arg ↓ site to generate biologically active proteins. Furin’s critical role in many cellular events associated with health disorders such as HIV, SARS, anthrax, and influenza as well as cancer has made inhibitors of this enzyme as therapeutic targets. To this date, the most potent inhibitor of furin is the bioengineered serpin (serine protease inhibitors) protein namely α -PDX. It was already demonstrated that the reactive site loop (RSL) of all serpins are prime interactive domains responsible for their protease inhibitory function. Therefore, the objective of the present study was to develop small peptides with the RSL structure of serpin α -PDX, as inhibitors of furin activity. Fifteen peptides were designed from reactive site loop structure of α-PDX (sequences 367-394) with different mutations in this site, and were synthesized using a solid-phase peptide synthesizer, and characterized by MALDI-tof mass spectrometry and amino acid analysis. The inhibitory effects of the designed peptides against furin activity were evaluated by spectroflourometry using QVEGF-C [Abz-QVHSIIRRßSLP-Y(NO2)-A-CONH2, Abz = 2-amino benzoic acid and Y(NO2) = 3-nitro tyrosine] as substrate. The results showed that all of the designed peptides inhibit furin activity with different efficacies in a time and concentration dependent pattern. Peptides containing His or straight alkyl side chain amino acids in positions P2, P3, P6 and P8 have higher efficacy for blocking furin activity in comparison with peptides containing Arg or Lys in that position. The study further revealed that the peptides inactivate furin in a slow tight binding pattern. Our study provides an alternate strategy for development of efficient peptide-based inhibitors of proprotein convertases such as furin.

Background: Proprotein convertase subtilisin / Kexin type 9 (PCSK9) inhibitors are efficacious lipid-lowering agents. This drug is related to improving the prognosis of patients with cardiovascular disease (CVD). The pur-pose of this meta-analysis was to systematically analyze the safety and efficacy of PCSK9 inhibitors in all pub-lished randomized controlled trials (RCTs). Methods: As of October 25, 2021, we searched PubMed, EMBASE, MEDLINE, Cochrane Library and web of science. Results: From 684 articles, we included 11 trials for meta-analysis, including 52511 participants (26938 in the PCSK9 inhibitor group and 25573 in the control group). In terms of effectiveness, PCSK9 inhibitors reduced the risk of major adverse cardiovascular events(MACE) (OR=0. 89, 95% Cl: 0. 83-0. 95, P=0. 0009), but did not significantly reduce the risk of cardiovascular death (OR=0. 95, 95% Cl: 0. 84-1. 07, P=0. 38) or all-cause death (OR=0. 93, 95% Cl: 0. 85-1. 03, P=0. 18),In terms of safety, PCSK9 did not increase the risk of treatment-emergent adverse events (TEAE)(OR=0. 98, 95% Cl: 0. 94-1. 02, P=0. 28). Conclusion: PCSK9 inhibitors can significantly reduce the risk of MACE in patients with high cardiovascular risk, which is well tolerated, but the impact on the risk of death is unclear.

Background: Melanoma Inhibitory Activity 3 regulates the plasma level of LDL cholesterol. The c.3169+315G>A single-nucleotide polymorphism of the MIA3 gene has been reported to be associated with serum coronary artery disease (CAD). However, there have been no studies analyzing the association of this polymorphism with CAD in Iranian individuals with CAD.Objectives: Therefore, in the present study we have investigated the potential protective effect of the rs3008621 MIA3polymorphism in 188 subjects with and without CAD.Materials and Methods: Genotyping of the MIA3 gene was undertaken using Taq Man real-time PCR in all subjects. Anthropometric and biochemical features, including HDL, LDL, and TG were assessed in all subjects.Results: The CAD patients had significantly (P<0.05) higher BMI and significantly higher levels of TG, LDL, SBP, and DBP, while the level of HDL was lower compared to that of the control group. the MIA3 gene polymorphism was not associated with CAD in our population sample.Conclusions: The MIA3 polymorphism is unlikely to play an important role in CAD in the Iranian population. However, further studies are needed in a larger population to confirm this.