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)
Article
Immunology
Solenne Vigne, Donovan Duc, Benjamin Peter, Jessica Rebeaud, Yannick Yersin, Florian Ruiz, Valentine Bressoud, Tinh-Hai Collet, Caroline Pot
Summary: This study investigated the effect of circulating cholesterol levels on multiple sclerosis (MS) using a mouse model. The results showed that blood cholesterol level does not have a direct role in neuro-inflammatory diseases, and the protective effects of statins in MS are not related to circulating cholesterol.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Medicine, General & Internal
Qidi Ying, Annalisa Ronca, Dick C. Chan, Jing Pang, Elda Favari, Gerald F. Watts
Summary: The study found that evolocumab and atorvastatin can decrease the capacity of whole plasma to efflux cellular cholesterol in normolipidaemic men, which may be mainly due to a decrease in the availability of apoB-100-containing lipoproteins.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Hematology
Karsten Schroer, Freek W. A. Verheugt, Dietmar Trenk
Summary: Lipid-lowering agents and antiplatelet drugs are standard treatments for secondary prevention of acute thrombotic events. Aspirin inhibits platelet-dependent thromboxane formation and improves endothelial oxygen defense, while statins reduce LDL-C levels and inhibit platelet function. PCSK9 antibodies target PCSK9, which impacts LDL-C plasma levels and platelet signaling. These drugs have synergistic effects and can reduce the incidence of atherothrombotic vascular events.
THROMBOSIS AND HAEMOSTASIS
(2023)
Review
Cardiac & Cardiovascular Systems
Sonia Sawant, Nelson Wang
Summary: This study found that lipid-lowering therapy (LLT) has similar cardiovascular event reduction effects across different ethnicities and regions, highlighting the importance of promoting LLT in at-risk populations.
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2023)
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
Genetics & Heredity
Navneet Kumar, Chandi C. Mandal
Summary: Cholesterol accumulation in cancer cells is associated with tumor development, while cholesterol-lowering drugs have been found to play a role in the prevention and treatment of various cancers. Dysregulation of Akt in cancer is common and targeting Akt is considered an effective approach for cancer therapy. Cholesterol-lowering drugs affect Akt expression and activation in cancer cells, showing anticancer activity in different types of cancers.
FRONTIERS IN GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Sai Sahana Sundararaman, Yvonne Doring, Emiel P. C. van Der Vorst
Summary: PCSK9, primarily secreted by hepatocytes, plays a role in regulating the degradation of the LDL receptor. Its effects on cardiovascular complications are not only LDLR-related, but also involve other independent pathways and processes.
Review
Food Science & Technology
Rana Shafabakhsh, Zeljko Reiner, Jamal Hallajzadeh, Liaosadat Mirsafaei, Zatollah Asemi
Summary: PCSK9 is a protease that increases LDLR degradation, leading to elevated LDL-cholesterol levels. Antibodies targeting PCSK9 can lower LDL-cholesterol, while nutraceuticals and anti-inflammatory agents are beneficial for treating dyslipidemia.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2021)
Review
Physiology
Carlos Noe Farfan-Morales, Carlos Daniel Cordero-Rivera, Jose Manuel Reyes-Ruiz, Arianna M. Hurtado-Monzon, Juan Fidel Osuna-Ramos, Arely M. Gonzalez-Gonzalez, Luis Adrian De Jesus-Gonzalez, Selvin Noe Palacios-Rapalo, Rosa Maria del Angel
Summary: Host lipid metabolism plays a crucial role in controlling flavivirus infections, with FDA-approved hypolipidemic drugs potentially serving as alternative treatments. Further understanding of the regulation between host lipid metabolism and signaling pathways triggered during infections is needed to explore the potential of lipid-lowering drugs as safe host-targeted antivirals.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Hematology
Yong-Xiang Chen, Chunhua Shi, Jingti Deng, Catherine Diao, Nadia Maarouf, Matthew Rosin, Vipul Shrivastava, Angie A. Hu, Sonya Bharadwa, Ayinuer Adijiang, Annegret Ulke-Lemee, Brenig Gwilym, Alexandria Hellmich, Christopher Malozzi, Zarah Batulan, Jonathan L. E. Dean, F. Daniel Ramirez, Jingwen Liu, William T. Gerthoffer, Edward R. O'Brien
Summary: The study demonstrates that HSP27 immunotherapy can lower cholesterol and PCSK9 levels primarily by increasing LDLR expression, and is associated with significant reductions in inflammation.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Shakir Ahamad, Shintu Mathew, Waqas A. Khan, Kishor Mohanan
Summary: In this review, we summarize recent developments in small-molecule PCSK9 inhibitors, focusing on their design, therapeutic effects, specific targets, and mechanisms of action.
DRUG DISCOVERY TODAY
(2022)
Article
Biology
Vi T. Tang, Joseph McCormick, Bolin Xu, Yawei Wang, Huan Fang, Xiao Wang, David Siemieniak, Rami Khoriaty, Brian T. Emmer, Xiao-Wei Chen, David Ginsburg
Summary: This study reveals the importance of SURF4 in the hepatic secretion of PCSK9 and APOB-containing lipoproteins. By generating mice with hepatic SURF4 deficiency, the researchers found that the absence of SURF4 leads to a severe defect in lipoprotein secretion, resulting in decreased plasma cholesterol and triglyceride levels. These findings highlight the potential of SURF4 as a therapeutic target in atherosclerotic cardiovascular diseases.
Review
Nutrition & Dietetics
Paul J. Nestel, Trevor A. Mori
Summary: This narrative review focuses on the role of diet in reducing LDLc concentrations in polygenic hypercholesterolemia. Statins and ezetimibe are effective drugs that can lower LDLc by more than 20%, providing potential alternatives to strict dieting. PCSK9 plays a significant role in LDL and lipid metabolism, and inhibitory monoclonal antibodies have shown promising results in lowering LDLc. A nutritional approach, such as substituting saturated fats with polyunsaturated fats, along with incorporating specific foods and supplements, has the potential to further reduce LDLc. Industry support and proper guidance from health professionals are necessary for the development and promotion of LDLc-lowering products.
Article
Biochemistry & Molecular Biology
Hanjing Liang, Qingmei Feng, Hui Guo, Jiangnan Lv, Lingxia Zhang, Qingxia Li, Jun Chi, Qiuyan Liu, Zhimin Wang, Liping Dai
Summary: This study isolated specific sesquiterpenoids from burdock leaves and demonstrated their anti-inflammatory and cholesterol-lowering activities. Compound 4 showed the strongest cholesterol-lowering effect and reduced the release of pro-inflammatory mediators by inhibiting specific signaling pathways. These findings provide chemical basis and scientific evidence for further research on burdock leaves as anti-atherosclerosis agents.
BIOORGANIC CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Paul F. Lebeau, Jae Hyun Byun, Khrystyna Platko, Paul Saliba, Matthew Sguazzin, Melissa E. MacDonald, Guillaume Pare, Gregory R. Steinberg, Luke J. Janssen, Suleiman A. Igdoura, Mark A. Tarnopolsky, S. R. Wayne Chen, Nabil G. Seidah, Jakob Magolan, Richard C. Austin
Summary: Caffeine inhibits the activation of SREBP2 to promote LDLc clearance and reduce the risk of cardiovascular disease.
NATURE COMMUNICATIONS
(2022)
Correction
Medicine, General & Internal
Dianna M. Milewicz, Alan C. Braverman, Julie De Backer, Shaine A. Morris, Catherine Boileau, Irene H. Maumenee, Guillaume Jondeau, Arturo Evangelista, Reed E. Pyeritz
NATURE REVIEWS DISEASE PRIMERS
(2022)
Review
Biochemistry & Molecular Biology
Zakaria Mougin, Julia Huguet Herrero, Catherine Boileau, Carine Le Goff
Summary: Extracellular matrix (ECM) in the vascular wall is a dynamic structure composed of different molecules. Metalloproteases, including ADAMTS proteins, play a key role in maintaining ECM homeostasis. This review focuses on the potential role of ADAMTS proteins in the development of thoracic and abdominal aortic aneurysms, providing new insights on the involvement of the ADAMTS family in these pathologies.
Article
Biochemistry & Molecular Biology
Justin R. Clark, Matthew Gemin, Amer Youssef, Santica M. Marcovina, Annik Prat, Nabil G. Seidah, Robert A. Hegele, Michael B. Boffa, Marlys L. Koschinsky
Summary: Elevated plasma lipoprotein(a) (Lp(a)) is an independent, causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Sortilin may play a role in determining plasma levels of Lp(a) and is associated with the secretion of apo(a) and apoB.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Yara Azar, Marie-Helene Gannage-Yared, Elie Naous, Carine Ayoub, Yara Abou Khalil, Elise Chahine, Sandy Elbitar, Youmna Ghaleb, Catherine Boileau, Mathilde Varret, Petra El Khoury, Marianne Abifadel
Summary: Elevated levels of PCSK9 in adults have been associated with increased LDL-C, TG, and worse cardiovascular outcomes. However, few studies have analyzed the relation between PCSK9 and lipid parameters in pediatric populations. This study found that serum PCSK9 levels were significantly correlated with TC, LDL-C, and non-HDL-C levels in Lebanese school children. Further studies are needed to determine if PCSK9 measurements have additional value in predicting cardiovascular outcomes in pediatric populations.
Review
Medicine, General & Internal
Marianne Abifadel, Catherine Boileau
Summary: Atherosclerotic cardiovascular disease is a major cause of death worldwide, and familial hypercholesterolemia (FH) is a commonly inherited disease with significant risks. Advances in genetic research have greatly improved the diagnosis and treatment of FH, providing more therapeutic options.
JOURNAL OF INTERNAL MEDICINE
(2023)
Article
Oncology
Yan Gu, Xiaozeng Lin, Ying Dong, Geoffrey Wood, Nabil G. Seidah, Geoff Werstuck, Pierre Major, Michael Bonert, Anil Kapoor, Damu Tang
Summary: This study found that tumor-derived PCSK9 is closely associated with the development of melanoma and promotes tumor growth by regulating cholesterol metabolism and influencing the immune system. The study also identified PCSK9 as a potential biomarker for predicting the efficacy of immune checkpoint blockade therapy.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Virology
Rachid Essalmani, Ursula Andreo, Alexandra Evagelidis, Mailys Le Devehat, Oscar Henrique Pereira Ramos, Carole Fruchart Gaillard, Delia Susan-Resiga, Eric A. Cohen, Nabil G. Seidah
Summary: This study investigates the involvement of cholesterol-regulating enzymes SKI-1 and PCSK9 in the entry of SARS-CoV-2. SKI-1 enhances cell-to-cell fusion by activating SREBP-2, while PCSK9 reduces cell-to-cell fusion by promoting the degradation of ACE2. Both SKI-1 and PCSK9 modulate SARS-CoV-2 entry through independent mechanisms.
Letter
Biochemistry & Molecular Biology
Anna Roubtsova, Corey A. Scipione, Damien Garcon, Michael B. Boffa, Nabil G. Seidah, Marlys L. Koschinsky, Annik Prat
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2023)
Article
Hematology
Oriane Marmontel, Yara Abou-Khalil, Olivier Bluteau, Bertrand Cariou, Valerie Carreau, Sybil Charriere, Eleonore Divry, Antonio Gallo, Philippe Moulin, Francois Paillard, Noel Peretti, Jean-Pierre Rabes, Mathilde Varret, Alain Carrie, Mathilde Di Filippo
Summary: This study investigated the phenotype of 21 adult patients who carried rare LDLR and APOE variants in a French cohort. The results showed that LDLR+APOE carriers had higher blood lipid levels and a higher incidence of premature atherosclerotic cardiovascular diseases compared to LDLR carriers alone.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
Y. Azar, Y. Abou-Khalil, Y. Ghaleb, S. El Bitar, M-N Lebel, C. Deschildre, S. Dupont, I. Guillas, W. Le Goff, C. Boileau, M. Varret, M. Abifadel, J-B Michel, P. El Khoury
Meeting Abstract
Cardiac & Cardiovascular Systems
Y. Ghaleb, S. El Bitar, A. Philippi, P. El Khoury, Y. Azar, M. Andrianirina, A. Loste, Y. Abou-Khalil, G. Nicolas, M. Le Borgne, P. Moulin, M. Di Filippo, S. Charriere, M. Farnier, C. Yelnik, V. Carreau, J. Ferrieres, J. -M. Lecerf, A. Derksen, G. Bernard, M. -S. Gauthier, B. Coulombe, D. Luetjohann, B. Finn, A. Boland, R. Olaso, J-F Deleuze, J-P Rabes, C. Boileau, M. Abifadel, M. Varret
Meeting Abstract
Biochemistry & Molecular Biology
Yara Azar, Yara Abou-Khalil, Mathilde Di-Filippo, Alain Carrie, Sophie Beliard, Catherine Boileau, Marianne Abi-Fadel, Jean-Pierre Rabes, Mathilde Varret
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)