Article
Medicine, Research & Experimental
Khadijeh Mahboobnia, Matteo Pirro, Ettore Marini, Francesco Grignani, Evgeny E. Bezsonov, Tannaz Jamialahmadi, Amirhossein Sahebkar
Summary: PCSK9 plays an important role in the development and progression of various cancers, highlighting its potential significance in cancer treatment. Inhibiting PCSK9 may help suppress the proliferation and invasion of tumor cells. However, the current lack of data on the role of PCSK9 in cancer and the impact of PCSK9 inhibition in cancer therapy limits our understanding of its effectiveness and safety.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Cardiac & Cardiovascular Systems
Angelos D. Karagiannis, Anurag Mehta, Devinder S. Dhindsa, Salim S. Virani, Carl E. Orringer, Roger S. Blumenthal, Neil J. Stone, Laurence S. Sperling
Summary: LDL-C is a causative factor for atherosclerotic cardiovascular disease, and pharmacological interventions can lower LDL-C levels. More patients are achieving very low LDL-C levels, with cardiovascular event reduction increasing log linearly in association with lowering LDL-C.
EUROPEAN HEART JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Nurjannatul Naim Kamaruddin, Nor Azwin Hajri, Yosie Andriani, Aina Farahiyah Abdul Manan, Tengku Sifzizul Tengku Muhammad, Habsah Mohamad
Summary: Atherosclerosis, caused by elevated plasma cholesterols, is a major factor in global cardiovascular disease mortality. While statins are commonly used to lower cholesterol levels, they may have adverse effects, prompting the search for new treatments. Research on the marine invertebrate Acanthaster planci suggests its potential in reducing cholesterol levels without causing harm to the liver.
Article
Chemistry, Medicinal
Nurjannatul Naim Kamaruddin, Lukman Hakim Mohd Din, Allicia Jack, Aina Farahiyah Abdul Manan, Habsah Mohamad, Tengku Sifzizul Tengku Muhammad
Summary: This study investigated the effects of a selected fraction of A. planci on PCSK9 gene expression, LDLR protein level, and LDL-C uptake. The results showed that the selected fraction reduced PCSK9 gene expression, increased LDLR protein level, and promoted LDL-C uptake. These findings suggest that the selected fraction has the potential to lower circulating LDL-C levels and may be a promising therapeutic intervention for preventing the progression of atherosclerosis.
Article
Cardiac & Cardiovascular Systems
Carlota Oleaga, Michael D. Shapiro, Joshua Hay, Paul A. Mueller, Joshua Miles, Cecilia Huang, Emily Friz, Hagai Tavori, Peter P. Toth, Cezary Wojcik, Bruce A. Warden, Jonathan Q. Purnell, P. Barton Duell, Nathalie Pamir, Sergio Fazio
Summary: This study investigated the mechanisms behind the increase in plasma PCSK9 levels in response to PCSK9i therapy. The findings suggest that PCSK9i enhances PCSK9 secretion, contributing to the elevated plasma PCSK9 levels in treated subjects.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Ali K. Jaafar, Romuald Techer, Kevin Chemello, Gilles Lambert, Steeve Bourane
Summary: This article comprehensively reviews the role of PCSK9 in lipid metabolism and cardiovascular health, as well as its potential roles in the central and peripheral nervous systems. It focuses particularly on its involvement in cerebrovascular and neurodegenerative diseases.
JOURNAL OF LIPID RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Sandra Hummelgaard, Joachim Pold Vilstrup, Camilla Gustafsen, Simon Glerup, Kathrin Weyer
Summary: Lowering blood cholesterol levels is crucial for reducing the risk of ASCVD, and PCSK9 plays a key role in cholesterol metabolism. Inhibiting PCSK9 has been shown to effectively reduce cholesterol levels and mitigate the risk of ASCVD events.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Carlota Oleaga, Joshua Hay, Emma Gurcan, Larry L. David, Paul A. Mueller, Hagai Tavori, Michael D. Shapiro, Nathalie Pamir, Sergio Fazio
Summary: Our study confirms that PCSK9_55 is predominantly formed extracellularly with a shorter half-life, while a small intracellular pool of PCSK9_55 remains non-secreted. Intracellularly retained PCSK9_55 exhibits reduced efficiency in inducing LDLR degradation compared to PCSK9_62.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Medicine, General & Internal
Meng Chai, Yongming He, Wang Zhao, Xuebin Han, Guoyan Zhao, Xueping Ma, Ping Qiao, Dongmei Shi, Yuyang Liu, Wei Han, Pei An, Haoyu Li, Shuling Yan, Qingyang Ma, Huan Deng, Lei Qian, Yujie Zhou
Summary: This study is the first randomized placebo-controlled clinical trial conducted in China to assess the efficacy and safety of tafolecimab in patients with HeFH. It was found that treatment with tafolecimab significantly reduced LDL-C levels and had a favorable safety profile in Chinese patients with HeFH.
Review
Biochemistry & Molecular Biology
Tadeja Sotler, Miran Sebestjen
Summary: Disturbances in lipid metabolism are a major risk factor for atherosclerotic cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important protein in lipid metabolism that is also involved in inflammation, endothelial dysfunction, and atherosclerotic plaque development. PCSK9 has been linked to inflammation and plays a role in the initiation and development of atherosclerotic lesions. Experimental studies have shown that an increased concentration of PCSK9 accelerates endothelial cell apoptosis and impairs endothelial function, creating conditions for the development of atherosclerosis. PCSK9 inhibitors can improve clinical outcomes through both lipid-dependent and lipid-independent pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, General & Internal
Safi U. Khan, Siva H. Yedlapati, Ahmad N. Lone, Qiukui Hao, Gordon Guyatt, Nicolas Delvaux, Geertruida E. (Trudy) Bekkering, Per Olav Vandvik, Irbaz Bin Riaz, Sheyu Li, Bert Aertgeerts, Nicolas Rodondi
Summary: This study aims to compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant.
BMJ-BRITISH MEDICAL JOURNAL
(2022)
Article
Multidisciplinary Sciences
Kiran Musunuru, Alexandra C. Chadwick, Taiji Mizoguchi, Sara P. Garcia, Jamie E. DeNizio, Caroline W. Reiss, Kui Wang, Sowmya Iyer, Chaitali Dutta, Victoria Clendaniel, Michael Amaonye, Aaron Beach, Kathleen Berth, Souvik Biswas, Maurine C. Braun, Huei-Mei Chen, Thomas Colace, John D. Ganey, Soumyashree A. Gangopadhyay, Ryan Garrity, Lisa N. Kasiewicz, Jennifer Lavoie, James A. Madsen, Yuri Matsumoto, Anne Marie Mazzola, Yusuf S. Nasrullah, Joseph Nneji, Huilan Ren, Athul Sanjeev, Madeleine Shay, Mary R. Stahley, Steven H. Y. Fan, Ying K. Tam, Nicole M. Gaudelli, Giuseppe Ciaramella, Leslie E. Stolz, Padma Malyala, Christopher J. Cheng, Kallanthottathil G. Rajeev, Ellen Rohde, Andrew M. Bellinger, Sekar Kathiresan
Summary: This study demonstrates the efficient and precise modification of disease-related genes in living cynomolgus monkeys using CRISPR base editors delivered in vivo via lipid nanoparticles. The results provide proof-of-concept for the potential therapeutic application of CRISPR base editors in making precise single-nucleotide changes in target genes, supporting a 'once-and-done' approach for the treatment of diseases.
Article
Cardiac & Cardiovascular Systems
Mario Luca Morieri, Valentina Perrone, Chiara Veronesi, Luca Degli Esposti, Margherita Andretta, Mario Plebani, Gian Paolo Fadini, Saula Vigili de Kreutzenberg, Angelo Avogaro
Summary: This study identified factors contributing to low achievement of LDL-cholesterol targets and underuse of lipid-lowering treatments in high- or very-high-cardiovascular risk patients. Gender, age, HDL-c, and triglyceride levels were found to delay statin prescriptions, indicating a need for modification to improve cardiovascular disease prevention. Late initiation of high-intensity treatments, especially in perceived low-risk patients, was highlighted as a key factor that needs to be addressed.
CARDIOVASCULAR DIABETOLOGY
(2021)
Article
Cell & Tissue Engineering
Meryl Roudaut, Salam Idriss, Amandine Caillaud, Aurore Girardeau, Antoine Rimbert, Benoite Champon, Amandine David, Antoine Leveque, Lucie Arnaud, Matthieu Pichelin, Xavier Prieur, Annik Prat, Nabil G. Seidah, Kazem Zibara, Cedric Le May, Bertrand Cariou, Karim Si-Tayeb
Summary: PCSK9, a key regulator of LDL cholesterol metabolism, is found to be highly expressed in undifferentiated hiPSCs. Inhibition of PCSK9 in hiPSCs leads to decreased phosphorylation of SMAD2 and cell proliferation, while overexpression of PCSK9 stimulates cell proliferation by regulating the expression of DACT2, an endogenous inhibitor involved in TGF beta-R1 lysosomal degradation. This highlights a new role of PCSK9 in cellular proliferation and development.
Article
Engineering, Environmental
Jian Li, Ying Xu, Na Li, Rui Zuo, Yuanzheng Zhai, Haiyang Chen
Summary: Through integrated in vitro, in vivo, and in silico assays, the study investigated the thyroid hormone-disrupting effects and mechanisms of 8 typical organophosphate esters (OPEs). It was found that these chemicals competitively bound to the membrane thyroid hormone receptor (mTR) and some OPEs also interacted with the nuclear thyroid hormone receptor (nTR). Molecular docking simulation supported these findings. In addition, in vivo analyses using zebrafish embryo development demonstrated the thyroid hormone-disrupting effects of OPEs and their possible association with mTR.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2022)