جستجوی مقالات مرتبط با کلیدواژه « pcsk9 » در نشریات گروه « پزشکی »

The effectiveness of immunotherapy for most cancer patients remains low, with approximately 10–30% of those treated surviving. Thus, much effort is being put into finding new ways to improve immune checkpoint therapy. Our review concludes that the inhibition of proprotein convertase subtilisin/Kexin type 9 (PCSK9), which plays a critical role in regulating cholesterol metabolism, can cause T cells to move toward tumors, with increased sensitivity to immune checkpoint therapies.We searched PubMed, NCBI, Scopus, and Google Scholar for the published articles without limitations on publication dates. We used the following terms: “PCSK9”, “Cancer”, “Immune Checkpoint”, and “Cancer Prognosis” in the title and/or abstract. Our search initially revealed 600 records on the subject and stored them in the used databases under EndNote X8 management software. We selected about 161 articles that were carefully read and among them, 76 were included in our research.We concluded that PCSK9 reduces the number of LDL receptors (LDL-R) on the cell surface, which is linked to its ability to regulate cholesterol levels in the body. Also, we discuss how suppressing PCSK9 leads to the MHC-1 accumulation on the surface of cancer cells, which results in T lymphocyte invasion. Finally, we believe that inhibiting PCSK9 may be an effective strategy for improving cancer immunotherapy.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) protein is one of the factors associated with oxidative stress and dyslipidemia disorders.

This study aimed to evaluate the lipid profile, PCSK9 levels, and oxidative stress in preeclampsia.

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.

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.

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.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulatory protein in lipid metabolism and a candidate gene in the etiology of cardiovascular diseases. The present study aimed to evaluate the prevalence and significance of PCSK9 rs505151 and rs11591147 variants with myocardial infarction (MI) risk in the Iranian population. Patients and

The frequency of the PCSK9 rs505151 and rs11591147 variants were compared between 600 cases of MI and 600 healthy age- and sex-matched individuals. Tetraprimer amplification refractory mutation system-polymerase chain reaction (T-ARMS PCR) was used for rs505151, and amplification refractory mutation system-polymerase chain (ARMS-PCR) was utilized to detect the rs11591147 polymorphism. Finally, SPSS and SHEsis software were applied for data analysis.

Carriers of the GG genotype of rs505151 polymorphism (OR: 1.57, 95% CI: 1.05– 2.35, P=0.02; age-adjusted; OR: 1.54, 95% CI: 1.03–2.32, P=0.03) and at least one G-allele including GG+AG vs. AA (OR: 1.54, 95% CI: 1.04–2.28, P=0.03; age-adjusted; OR: 1.51, 95% CI: 1.01–2.24, P=0.04) have an increased risk of MI. No association between PCSK9 rs505151 alleles and MI risk was observed. The ratio of individuals with the rs11591147GT variant was higher in healthy individuals vs. patients with MI (48.6% vs. 41.7%), indicating a reduced risk of developing MI (OR: 0.75; 95% CI: 0.59–0.95; P=0.01; age-adjusted; OR: 0.74; 95% CI: 0.58– 0.95; P=0.01). The carriers of at least one T allele (TT+GT vs. GG) (OR: 0.78; 95% CI: 0.62–0.98; P=0.03; age-adjusted; OR: 0.78; 95% CI: 0.62–0.98; P=0.03) showed a significant reduction in MI risk. The allelic frequencies at this polymorphic site did not differ between MI patients and healthy counterparts. No association was found between the haplotypes constructed from the alleles of these two polymorphisms.

Our study provides the first evidence that PCSK9 gene polymorphisms may serve as independent prognostic markers for MI patients in Iran.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), as a vital modulator of low-densitylipoprotein cholesterol (LDL-C) , is raised in hepatocytes and released into plasma where it bindsto LDL receptors (LDLR), leading to their cleavage. PCSK9 adheres to the epidermal growthfactor-like repeat A (EGF-A) domain of the LDLR which is confirmed by crystallography. LDLRexpression is adjusted at the transcriptional level through sterol regulatory element bindingprotein 2 (SREBP-2) and at the post translational stages, specifically through PCSK9, and theinducible degrader of the LDLR PCSK9 inhibition is an appealing new method for reducing theconcentration of LDL-C. In this review the role of PCSK9 in lipid homeostasis was elucidated, theeffect of PCSK9 on atherosclerosis was highlighted, and contemporary therapeutic techniquesthat focused on PCSK9 were summarized. Several restoration methods to inhibit PCSK9 havebeen proposed which concentrate on both extracellular and intracellular PCSK9, and theyinclude blockage of PCSK9 production by using gene silencing agents and blockage of it’sbinding to LDLR through antibodies and inhibition of PCSK9 autocatalytic processes by tinymolecule inhibitors.

Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9), a serine protease, plays an important role in the regulation of cholesterol metabolism. PCSK9 interacts with Low Density Lipoprotein Receptor (LDLR) on the surface of hepatocytes, promoting its lysosomal degradation, thus leading to the accumulation of cholesterol outside the cells followed by hypercholesterolemia.

This study aimed to assess three polymorphisms (rs662145, rs505151, and rs562556) of the PCSK9 gene in two Iranian ethnic groups (Turk and Lur) with Coronary Artery Disease (CAD) in Fars province.

In this cross-sectional study, 114 Turk and 73 Lur patients with CAD were selected based on the clinical examination by a cardiologist. The three polymorphisms were assessed by Real-Time Polymerase Chain Reaction (PCR) method using specific primers and probes. Chi-square test was used to compare the two groups regarding the qualitative variables. All analyses were performed using the SPSS 18 software and P < 0.05 was considered to be statistically significant.

The results revealed no significant difference between the Turk and Lur groups regarding the three polymorphisms (P > 0.05). In addition, no significant relationship was observed between the rs662145 polymorphism and clinical characteristics like family history of CAD, diabetes, Myocardial Infarction (MI), Body Mass Index (BMI), and High Density Lipoprotein (HDL) level (P > 0.05). However, a significant relationship was found between the rs505151 polymorphism and MI (P = 0.03) and Low Density Lipoprotein (LDL) level (P = 0.04) in Turk patients. Nonetheless, no significant correlation was detected between the rs505151 polymorphism and clinical parameters (P > 0.05). The results also showed no significant relationship between the rs505151 polymorphism and clinical parameters in Lur patients (P > 0.05). Analysis of the rs562556 polymorphism also revealed no significant relationship between this polymorphism and clinical characteristics in both Turk and Lur samples (P > 0.05).

rs662145 polymorphism was associated with LDL and Triglyceride (TG) levels in both Turk and Lur samples. Besides, rs505151 polymorphism was correlated to LDL level and MI in Turk patients. Therefore, in addition to other predisposing genes to CAD, analysis of PCSK9 mutations can be used for predicting hypercholesterolemia and premature CAD.