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)
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.
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
Genetics & Heredity
Arman Moradi, Majid Maleki, Zahra Ghaemmaghami, Zahra Khajali, Feridoun Noohi, Maryam Hosseini Moghadam, Samira Kalyinia, Seyed Javad Mowla, Nabil G. Seidah, Mahshid Malakootian
Summary: Genetic mutations in LDLR and PCSK9 genes exhibit diversity in Iranian patients with FH, potentially leading to the development of FH and early-onset CAD. A pathogenic mutation in the LDLR gene was found to be cosegregated in a family. Genetic testing and reports on nucleotide alterations are limited in the Iranian population.
FRONTIERS IN GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Alessandro Morotti, Cristina Barale, Elena Melchionda, Isabella Russo
Summary: This article discusses the association between oxidative stress and hypercholesterolemia, as well as platelet hyperreactivity, and explores the impact of lipid-lowering therapies on thrombogenesis, emphasizing the significance of oxidative stress-related mechanisms in platelet function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Chemistry, Medicinal
Sabrina E. Iskandar, Albert A. Bowers
Summary: In this article, we discuss the successful development of an mRNA display-derived clinical candidate by Merck & Co., which is a bioavailable inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9). The challenges in the chemical and pharmacological aspects of bringing this compound to trials are highlighted, and the current outlook for mRNA display-based therapeutic development is examined.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
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
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.