scholarly journals PCSK9: A Potential Therapeutic Target for Sepsis

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuan Yuan ◽  
Wei Wu ◽  
Shanshan Sun ◽  
Yi Zhang ◽  
Zhi Chen

Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host response to infection. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is often upregulated in the presence of sepsis and infectious diseases. In sepsis, PCSK9 degraded the low-density lipoprotein cholesterol (LDL) receptors (LDL-R) of the hepatocytes and the very low-density lipoprotein cholesterol receptors (VLDL-R) of the adipocytes, which then subsequently reduced pathogenic lipid uptake and clearance/sequestration. Moreover, it might improve cholesterol accumulation and augment toll-like receptor function in macrophages, which supported inflammatory responses. Accordingly, PCSK9 might show detrimental effects on immune host response and survival in sepsis. However, the exact roles of PCSK9 in the pathogenesis of sepsis are still not well defined. In this review, we summarized the literatures focusing on the roles of PCSK9 in sepsis. Our review provided an additional insight in the role of PCSK9 in sepsis, which might serve as a potential target for the treatment of sepsis.

2018 ◽  
Vol 268 ◽  
pp. 196-206 ◽  
Author(s):  
Yu-Xin Xu ◽  
Valeska Redon ◽  
Haojie Yu ◽  
William Querbes ◽  
James Pirruccello ◽  
...  

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1216.2-1217
Author(s):  
K. Gudkevich ◽  
N. Martusevich ◽  
E. Dashkevich

Background:Avascular necrosis (AN) is a disabling disease affecting predominantly young men. It steadily progresses to secondary osteoarthritis. The rate of disability is high, because hip joint is most commonly affected by AN; moreover, the rate of bilateral hip joint involvement is also high. The key event in the pathogenesis of AN is circulation disorder which results in ischemia and, furthermore, death of bone tissue.Nowadays the data about lipid metabolism in patients with AN. Besides, there is contradictory data about the role of homocysteine in the risk of cardiovascular events. Based on these, it is topical to investigate lipid metabolism and endothelial function in patients with AN.Objectives:The aim of the present study was to investigate lipid metabolism and endothelial function in patients with different stages of AN in order to find risk factors for incidence and progression of this disease.Methods:We recruited 41 patients with AN of the femoral head or femoral condyles aged 51 (35-64) years, 56,1% (n=23) were male. The inclusion criteria was diagnosis of AN confirmed by X-Ray, CT or MRI. The exclusion criteria were: traumatic AN, Legg-Calve-Pertes disease, connective tissue systemic diseases. Also we divided patients into subgroups with early (39% (n=16)) and late (61,0% (n=25)) stages of AN.Patients of the control group (n=32) were comparable by age and gender. The data was proceeded using non-parametric and descriptive statistics. We evaluated the following parameters: homocysteine, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, cholesterol ratio, apolipoprotein A1, apolipoprotein B.Results:In patients with AN we observed higher level of homocysteine (12,119 (7,771-14,38) vs. 7,911 (6,612-10,54) mcmol/l, p=0,05). The results are consistent with the data that higher homocyseine level is associated with higher risk for cardiovascular events (1). There is literature data about elevated homocysteine level in patients with AN, which was associated with lower levels of vitamin B12 and folic acid. Thus, interpretation of homocystene significance is more reliable in association with vitamin B12 and folic acid levels.Also, we observed that level of HDLP-C is higher in patients with early stages than in pate stages of AN (1,55 (1,31-1,57) vs. 1,23 (1,04-1,36) mmol/l, р=0,04). Thus, HDLP-C can be interpreted as a protective factor against contralateral joint involvement in AN patients. The data obtained is consistent with the existing data that HDLP-C lowers the risk for cardiovascular events.Conclusion:The data obtained indicate a significant role of dyslypidemia in the pathogenesis of AN in the context of vascular theory.References:[1]Steven G. Chrysant & George S. Chrysant (2018) The current status of homocysteine as a risk factor for cardiovascular disease: a mini review, Expert Review of Cardiovascular Therapy, 16:8, 559-565, DOI: 10.1080/14779072.2018.1497974.[2]Narayanan, A., Khanchandani, P., Borkar, R.M.et al.Avascular Necrosis of Femoral Head: A Metabolomic, Biophysical, Biochemical, Electron Microscopic and Histopathological Characterization.Sci Rep7, 10721 (2017).https://doi.org/10.1038/.Disclosure of Interests:Katsiarina Gudkevich: None declared, Natalia Martusevich Shareholder of: k, Elena Dashkevich: None declared


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