Article
Biochemistry & Molecular Biology
Vittoria Cammisotto, Francesco Baratta, Paola G. Simeone, Cristina Barale, Enrico Lupia, Gioacchino Galardo, Francesca Santilli, Isabella Russo, Pasquale Pignatelli
Summary: PCSK9 is involved in cholesterol metabolism and plays a role in the development of atherosclerosis and atherothrombotic processes, promoting plaque formation and oxidative stress.
Article
Medical Laboratory Technology
Antonin Jabor, Tereza Vackova, Zdenek Kubicek, Jitka Komrskova, Marek Protus, Janka Franekova
Summary: The study evaluated the biological variation of serum PCSK9, finding a high within-subject variability in healthy individuals, suggesting that common reference intervals can be used to interpret its values.
CLINICA CHIMICA ACTA
(2021)
Article
Medical Laboratory Technology
Jia-ni Xu, Ting-ting Wang, Hong Shu, Shun-yi Shi, Li-chan Tao, Jian-Jun Li
Summary: Diabetes mellitus (DM) is strongly associated with atherosclerotic cardiovascular disease (ASCVD), and the protein PCSK9 has been identified as a key regulator of LDL-C levels and a potential target for improving cardiovascular outcomes. Recent studies have also linked PCSK9 to glucose metabolism, and clinical trials suggest that PCSK9 inhibitors are more effective in treating patients with DM. This review summarizes the current findings on the association between PCSK9 and glucose metabolism, including the effects of PCSK9 genetic mutations, plasma PCSK9 concentrations, and glucose-lowering drugs on metabolic parameters, as well as the impact of PCSK9 inhibitors on cardiovascular outcomes in patients with DM.
CLINICA CHIMICA ACTA
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Jia Peng, Cheng-Gang Zhu, Jian-Jun Li
Summary: Increasing data suggest that PCSK9 may play a role in the development of type 2 diabetes and be associated with clinical outcomes in diabetic patients, but there is currently no general agreement about the association of PCSK9 with T2DM. The utility of circulating PCSK9 concentration as a predictor for the risk of new-onset T2DM should be considered clinically prudent.
CARDIOVASCULAR DIABETOLOGY
(2021)
Review
Pharmacology & Pharmacy
Fang Jia, Si-Fan Fei, De-Bing Tong, Cong Xue, Jian-Jun Li
Summary: PCSK9 increases circulating LDL-C levels by degrading LDL receptors and has direct effects on atherosclerosis and coronary plaque inflammation. Emerging data show higher PCSK9 concentrations in women than men, suggesting potential sex differences in PCSK9 roles and clinical implications.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Miao Yu, Wenjing Tang, Wei Liang, Baikang Xie, Ran Gao, Peiwu Ding, Xiaoying Gu, Min Wang, Shuang Wen, Peng Sun
Summary: Proprotein convertase subtilisin kexin type 9 (PCSK9) was initially known for its role in regulating cholesterol metabolism, but recent studies have shown its involvement in inflammatory and autoimmune diseases unrelated to cholesterol alterations. This study aims to investigate the roles and mechanisms of PCSK9 in myocarditis and found that PCSK9 inhibition can ameliorate the severity of myocarditis by reducing Th17 cell differentiation. PCSK9 appears to be a promising target for treating myocarditis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Coen van Solingen, Scott R. Oldebeken, Alessandro G. Salerno, Amarylis C. B. A. Wanschel, Kathryn J. Moore
Summary: The discovery of PCSK9 and its role in LDL regulation has led to the rapid development of therapeutic PCSK9 inhibitors. Research has identified certain microRNAs that can reduce PCSK9 expression, leading to increased LDLR expression in hepatic cells, which may have therapeutic implications for manipulating LDLR expression and cholesterol levels in the liver.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Cell Biology
Liuxin Ning, Yanting Zou, Shuyu Li, Yue Cao, Beili Xu, Shuncai Zhang, Yu Cai
Summary: The study aimed to investigate the mechanism of anti-PCSK9 treatment on liver fibrosis by inhibiting hypoxia-induced autophagy. The results showed that anti-PCSK9 treatment could alleviate liver inflammation and fibrosis by regulating the AMPK/mTOR/ULK1 signaling pathway to reduce hypoxia-induced autophagy in hepatocytes.
Article
Endocrinology & Metabolism
Yiming Wu, Jie Shi, Qing Su, Zhen Yang, Li Qin
Summary: This study found that circulating PCSK9 levels were significantly higher in pregnant women with gestational diabetes mellitus (GDM) compared to those with normal glucose tolerance. The levels of PCSK9 were positively correlated with fasting plasma glucose, glycated hemoglobin, total cholesterol, and low-density lipoprotein cholesterol in the GDM group. Logistic regression analysis showed that age and serum PCSK9 levels were independently associated with GDM. The study suggests a potential link between PCSK9 and GDM.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zhicai Feng, Xiangyu Liao, Juan Peng, Jingjing Quan, Hao Zhang, Zhijun Huang, Bin Yi
Summary: Our research demonstrates that PCSK9 contributes to aggravated inflammation in the kidneys through triggering mitochondrial DNA damage and activating the cGAS-STING signaling pathway in diabetic nephropathy (DN). Inhibiting PCSK9 with mAbs or siRNA effectively reduces inflammation and delays the progression of DN. Furthermore, the inhibition of STING significantly blocks the inflammation triggered by HGPA in HK-2 cells.
Article
Cardiac & Cardiovascular Systems
Alex K. K. Leung, Yuan Chao Xue, Antyrah de Guzman, Guilherme Grzelkovski, HyeJin Julia Kong, Kelly R. Genga, James A. Russell, John H. Boyd, Gordon A. Francis, Keith R. Walley
Summary: This study found that PCSK9 reduces the uptake of LPS in vascular endothelial cells through LDLR-mediated endocytosis, leading to a decrease in the inflammatory response. This suggests that PCSK9 inhibition may have additional effects on vascular endothelial inflammation.
Article
Medicine, General & Internal
Jonathan Grimm, Georg Peschel, Martina Mueller, Doris Schacherer, Reiner Wiest, Kilian Weigand, Christa Buechler
Summary: This study found that serum PCSK9 levels were associated with liver injury and inflammation in cirrhotic HCV patients, but not with LDL levels. After DAA therapy, PCSK9 decreased and LDL increased in non-cirrhotic HCV patients, while no changes were observed in the cirrhotic group.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, General & Internal
Thomas S. Metkus, Bo Soo Kim, Steven R. Jones, Seth S. Martin, Steven P. Schulman, Thorsten M. Leucker
Summary: This study aimed to investigate the association between proprotein convertase subtilisin/kexin type 9 (PCSK9) and mortality and ICU outcomes in patients with acute respiratory distress syndrome (ARDS). The results showed that PCSK9 levels were not associated with mortality in ARDS patients, but higher PCSK9 levels were associated with fewer ICU and ventilator free days.
FRONTIERS IN MEDICINE
(2022)
Article
Immunology
Yanqiang Zou, Zhang Chen, Xi Zhang, Jizhang Yu, Heng Xu, Jikai Cui, Yuan Li, Yuqing Niu, Cheng Zhou, Jiahong Xia, Jie Wu
Summary: The study found that PCSK9 is upregulated in a mouse model of GVD, and PCSK9 knockout reduces vascular occlusion, suggesting that PCSK9 may be a promising target for the treatment of GVD.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Oliver C. McGehee, Hassan Y. Ebrahim, Ashkan H. Rad, Khaldoun S. Abdelwahed, Ethar A. Mudhish, Judy A. King, Iman E. Helal, Sharon A. Meyer, Khalid A. El Sayed
Summary: Pseurotin A (PsA), a natural compound extracted from Aspergillus and Penicillium species, has shown to suppress the expression and protein-protein interaction (PPI) of PCSK9, leading to an anti-hypercholesterolemic effect. In vitro toxicity studies on non-tumor prostate and colon cells revealed high cellular death at higher concentrations of PsA, while acute organ toxicity was not observed in mice following oral dosing.