16 papers · ranked by Valyu relevance
Xuhui Bao, Yongjun Liang, Hanman Chang, Tianji Cai + 6 more
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has evolved as a pivotal enzyme in lipid metabolism and a revolutionary therapeutic target for hypercholesterolemia and its related cardiovascular diseases (CVD). This comprehensive review delineates the intricate roles and wide-ranging implications of PCSK9…
James Latimer, Jonathan A. Batty, R. Dermot G. Neely, Vijay Kunadian
Reducing plasma levels of low-density lipoprotein cholesterol (LDL-C) remains the cornerstone in the primary and secondary prevention of cardiovascular disease. However, lack of efficacy and adverse effects mean that a substantial proportion of patients fail to achieve acceptable LDL-C levels with currently available…
Nabil G. Seidah
During an exhaustive PCR-based homology search to the PCSKs, in mouse, rat and human cell lines in 2002 (reported in early 2003), 5 we cloned a novel cDNA sequence encoding a 24-25% identical catalytic subunit (260 aa) to the subtilases SKI-1/S1P, PC7, and tripeptidyl peptidase II. Using a protein BLAST program…
Kevin Saitoski, Maria Ryaboshapkina, Ghaith M. Hamza, Andrew F. Jarnuczak + 9 more
Proprotein convertase subtilisin/kexin 9 (PCSK9) is involved in the degradation of LDLR. However, PCSK9 can target other proteins in a cell-type specific manner. While PCSK9 has been detected in pancreatic islets, its expression in insulin-producing pancreatic beta cells is debated. Herein, we studied PCSK9 expression…
Chengfeng Qiu, Pingyu Zeng, Xiaohui Li, Zhen Zhang + 6 more
'Zhou Y. F. Peng' 'Yapei Li' 'Yeshuo Ma' 'Yiping Leng' 'Ruifang Chen'] Background PCSK9 rs505151 and rs11591147 polymorphisms are identified as gain- and loss-of-function mutations, respectively. The effects of these polymorphisms on serum lipid levels and cardiovascular risk remain to be elucidated. Methods In this…
Dhrubajyoti Bandyopadhyay, Kumar Ashish, Adrija Hajra, Arshna Qureshi + 1 more
'Arshna Qureshi' 'Raktim K. Ghosh'] PCSK9 inhibitors, monoclonal antibodies, are novel antihypercholesterolemic drugs. FDA first approved them in July 2015. PCSK9 protein (692-amino acids) was discovered in 2003. It plays a major role in LDL receptor degradation and is a prominent modulator in low-density lipoprotein…
Hongmei Li, Huili Liu, Wenxin Xu, Yuanjun Zeng + 6 more
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a central regulator of low-density lipoprotein (LDL) cholesterol metabolism, yet the functional consequences of many clinically observed PCSK9 variants remain unknown. To establish a rigorous system for quantitative variant assessment, we generated a PCSK9…
Rhogerry Deshycka, Valentino Sudaryo, Nai-Jia Huang, Yushu Xie + 5 more
Low plasma levels of Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) are associated with decreased low-density lipoprotein (LDL) cholesterol and a reduced risk of cardiovascular disease. PCSK9 binds to the epidermal growth factor-like repeat A (EGFA) domain of LDL receptors (LDLR), very low-density lipoprotein…
Isabela Bensenor, Kallyandra Padilha, Isabella Ramos Lima, Raul Dias Santos + 9 more
'Raul Dias Santos' 'Gilles Lambert' 'Stéphane Ramin-Mangata' 'Marcio S Bittencourt' 'Alessandra C Goulart' 'Itamar S. Santos' 'Jose G Mill' 'Jose E Krieger' 'Paulo A. Lotufo' 'Alexandre C. Pereira'] Pharmacological inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is an established therapeutic option…
Isabela Bensenor, Kallyandra Padilha, Isabella Ramos Lima, Raul Dias Santos + 9 more
Pharmacological inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is an established therapeutic option to treat hypercholesterolemia and plasma PCSK9 levels have been implicated in cardiovascular disease incidence. A number of genetic variants within the PCSK9 gene locus have been shown to modulate…
Marcin Basiak, Michał Kosowski, Marcin Cyrnek, Łukasz Bułdak + 5 more
'Mateusz Maligłówka' 'Grzegorz Machnik' 'Bogusław Okopień' 'Sabata Pierno' 'Olimpia Musumeci'] Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are a group of drugs whose main mechanism of action is binding to the PCSK-9 molecule, which reduces the degradation of the low-density lipoprotein receptor…
Abhiram S. Rao, Daniel Lindholm, Manuel A. Rivas, Joshua W. Knowles + 2 more
PCSK9 inhibitors are a potent new therapy for hypercholesterolemia and have been shown to decrease risk of coronary heart disease. Although short-term clinical trial results have not demonstrated major adverse effects, long-term data will not be available for some time. Genetic studies in large well-phenotyped biobanks…
Amand F Schmidt, Michael V Holmes, David Preiss, Daniel Swerdlow + 164 more
We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Fourteen…
Peter Emil Carstensen, Jacob Bendsen, Laura Hjort Blicher, Kim Kristensen + 1 more
'Kim Kristensen' 'John Bagterp Jørgensen'] Abstract: Cardiovascular diseases are the leading cause of death. Increased levels of plasma cholesterol are consistently associated with an increased risk of cardiovascular disease. As a result, it is imperative that studies are conducted to determine the best course of…
Janet Sasso, Barbara Ambrose, Rumiana Tenchov, Ruchira Datta + 3 more
In the last decade, there has been a shift in research, clinical development, and commercial activity to exploit the many roles of RNA in physiology for use in medicine. With the rapid success in the development of lipid-RNA nanoparticles for mRNA vaccines against COVID-19 and with several approved RNA-based drugs, RNA…
Brian A. Ference, George Davey Smith, Michael V. Holmes, Alberico L. Catapano + 2 more
'Alberico L. Catapano' 'Kausik K. Ray' 'Stephen J. Nicholls'] From the Centre for Naturally Randomized Trials, University of Cambridge, Cambridge, U.K. (B.A.F.); MRC Integrative Epidemiology Unit, University of Bristol, Bristol, U.K. (G.D.S.); MRC Population Health Research Unit and the Clinical Trial Service Unit and…