Article
Pharmacology & Pharmacy
Benjamin Benhuri, Hiroki Ueyama, Hisato Takagi, Alexandros Briasoulis, Toshiki Kuno
Summary: Among patients not on statins, PCSK9i was more effective in reducing LDL-C levels compared to ezetimibe, with a more significant effect seen in statin intolerant patients. There were no significant differences in LDL-C reduction between different dosages of PCSK9i.
CURRENT VASCULAR PHARMACOLOGY
(2021)
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)
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
Rolf Schreckenberg, Annemarie Wolf, Tamara Szabados, Kamilla Gomori, Istvan Adorjan Szabo, Gergely Agoston, Gabor Brenner, Peter Bencsik, Peter Ferdinandy, Rainer Schulz, Klaus-Dieter Schlueter
Summary: Hypoxia upregulates PCSK9 in the heart, which affects myocyte function. Genetic deletion of PCSK9 or antagonism of circulating PCSK9 reduces reperfusion injury. A high-fat diet decreases survival rate during reperfusion, likely due to increased MMP9 activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Rafael Saup, Nidhi Nair, Jingyi Shen, Anja Schmaus, Wilko Thiele, Boyan K. Garvalov, Jonathan P. Sleeman
Summary: The role of circulating osteopontin (cOPN) in melanoma progression was studied. It was found that increased cOPN promotes primary tumor growth but does not significantly affect spontaneous metastasis of melanoma cells to lymph nodes or lungs.
Article
Multidisciplinary Sciences
Elisabeth Veiz, Susann-Kristin Kieslich, Dirk Czesnik, Christoph Herrmann-Lingen, Thomas Meyer, Julia Staab
Summary: In this randomized, sham-controlled study, the effects of acute transcutaneous vagus nerve stimulation (tVNS) on serum aldosterone were examined. The results showed that aldosterone levels decreased after stimulation, regardless of the mode of stimulation. However, the difference between active and sham stimulation was not significant. Furthermore, serum aldosterone levels were found to vary depending on age and sex.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Emilie Wong Chong, France-Helene Joncas, Nabil G. Seidah, Frederic Calon, Caroline Diorio, Anne Gangloff
Summary: This study aimed to compare the circulating levels of lipid-related factors in women with breast cancer and those with premalignant or benign breast lesions. The results showed that PCSK9 levels were significantly higher in women with breast cancer and positively correlated with disease severity. However, no association was found between ANGPTL3 or Lp(a) levels and breast disease status.
Article
Nutrition & Dietetics
Amelie Rudolph, Andreas Stengel, Maria Suhs, Selina Schaper, Ellen Woelk, Matthias Rose, Tobias Hofmann, Maria Scherma
Summary: This study investigated the relationship between the Neuronatin gene and eating disorders and found a positive correlation between Neuronatin and body weight and fat mass. However, no significant correlations were found between Neuronatin and psychological outcomes in patients with eating disorders and obesity.
Article
Immunology
Yongsheng Luo, Feifei Luo, Kuanxin Zhang, Shilei Wang, Haojie Zhang, Xianlei Yang, Wenjun Shang, Junxiang Wang, Zhigang Wang, Xinlu Pang, Yonghua Feng, Lei Liu, Hongchang Xie, Guiwen Feng, Jinfeng Li
Summary: Circulating IL-10(+) Breg levels are a more appropriate indicator for assessing resistance to AMR after kidney transplantation compared to Bregs. Kidney B cell and IL-10 infiltration, as well as high expression of CXCL13, were associated with AMR. Furthermore, circulating IL-10(+) Bregs remained elevated during the 90-day post-operation period, contributing to immune homeostasis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Orthopedics
J. Zhou, C. Liu, Y. Sun, M. Francis, M. S. Ryu, A. Grider, K. Ye
Summary: Genetically determined copper and zinc status were positively associated with osteoarthritis, particularly increasing the risk of localized OA, while an increase in calcium levels decreased the risk of localized OA.
OSTEOARTHRITIS AND CARTILAGE
(2021)
Article
Biochemistry & Molecular Biology
Claudette Cantin, Maria Jesus Garchitorena, Rodrigo Escalona, Jorge A. Carvajal, Sebastian E. Illanes, Jaime Gutierrez, Andrea Leiva
Summary: Maternal supraphysiological hypercholesterolemia (MSPH) during pregnancy is associated with elevated levels of low-density lipoprotein (LDL) and increased levels of proprotein convertase subtilisin/kexin type 9 (PCSK9). The altered composition and function of LDL in MSPH women may contribute to maternal vascular dysfunction.
Article
Cardiac & Cardiovascular Systems
Wenfang Ma, Xiying Guo, Yiming Ma, Zhao Hu
Summary: PCSK9 mAbs effectively reduce the risk of MACEs, stroke, and myocardial infarction in patients at high cardiovascular risk compared to placebo. However, they are not superior to ezetimibe in preventing adverse cardiovascular events, highlighting the need for RCTs with long-term follow-up and cardiovascular events as the research endpoint.
Article
Physiology
Sinje Biss, Marc Teschler, Melina Heimer, Thomas Thum, Christian Baer, Frank C. Mooren, Boris Schmitz
Summary: This study aimed to evaluate the long-term effects of EMS on circulating miRNA levels. The results showed that a single EMS session induces specific long-lasting changes in miR-206 and miR-133a involved in muscle proliferation and differentiation, but does not affect cardiovascular miRNAs.
JOURNAL OF APPLIED PHYSIOLOGY
(2023)
Review
Immunology
Seyyed Mostafa Arabi, Mahla Chambari, Mahsa Malek-Ahmadi, Leila Sadat Bahrami, Vahid Hadi, Manfredi Rizzo, Amirhossein Sahebkar
Summary: This study conducted a systematic review and meta-analysis to evaluate the effect of statin therapy in combination with ezetimibe on CRP and hs-CRP levels. The results showed that the combination therapy significantly reduced the levels of hs-CRP and overall CRP, suggesting its potential in suppressing inflammation.
INFLAMMOPHARMACOLOGY
(2022)
Article
Oncology
Jung Min Suh, Yelin Son, Jung-Yeon Yoo, Yookyung Goh, Nabil G. Seidah, Sanghyuk Lee, Yun Soo Bae
Summary: The study reveals that Ahnak regulates tumor metastasis through controlling the expression of PCSK9. Ahnak(-/-) mice show higher resistance to B16F10 melanoma cell pulmonary metastasis, while PCSK9 plays a crucial role in the metastasis of melanoma cells.
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)
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
Virology
Rachid Essalmani, Jaspreet Jain, Delia Susan-Resiga, Ursula Andreo, Alexandra Evagelidis, Rabeb Mouna Derbali, David N. Huynh, Frederic Dallaire, Melanie Laporte, Adrien Delpal, Priscila Sutto-Ortiz, Bruno Coutard, Claudine Mapa, Keith Wilcoxen, Etienne Decroly, Tram Nq Pham, Eric A. Cohen, Nabil G. Seidah
Summary: The spike protein of SARS-CoV-2 plays a crucial role in infecting the lungs and other tissues by binding to the ACE2 receptor. Cleavage of the spike protein at S1/S2 and S2' sites is important for viral entry and fusion. This study identifies the fusion activation site S2' as KPSKR815 down arrow and demonstrates that its cleavage is enhanced by ACE2 engagement. The combination of furin and TMPRSS2 inhibitors shows promise as potent antivirals against SARS-CoV-2.
JOURNAL OF VIROLOGY
(2022)
Review
Peripheral Vascular Disease
Nabil G. Seidah, Damien Garcon
Summary: Since the discovery of PCSK9 in 2003, it has been found to play roles not only in regulating LDL-cholesterol, but also in inflammation, pathogen infections, and cellular proliferation in various cancers and associated metastases.
CURRENT ATHEROSCLEROSIS REPORTS
(2022)
Review
Peripheral Vascular Disease
Ioanna Gouni-Berthold, Jonas Schwarz, Heiner K. Berthold
Summary: This review summarizes recent data on PCSK9 monoclonal antibodies and evaluates their relevance in the era of nucleic acid-based therapy for lipid lowering and prevention of cardiovascular disease. New methods of PCSK9 inhibition based on nucleic acid therapeutics are reported, and the clinical relevance of PCSK9 antibodies is discussed. Although other forms of PCSK9 inhibition are still in early phases of development, PCSK9-mAb remains the only tool with positive cardiovascular outcome trials.
CURRENT ATHEROSCLEROSIS REPORTS
(2022)
Article
Engineering, Biomedical
Jessie R. Davis, Xiao Wang, Isaac P. Witte, Tony P. Huang, Jonathan M. Levy, Aditya Raguram, Samagya Banskota, Nabil G. Seidah, Kiran Musunuru, David R. Liu
Summary: Compact adenine base editors (ABEs) encoded within size-optimized genomes of adeno-associated viruses (AAVs) enable therapeutic base editing in mice at low doses and high editing efficiencies, simplifying AAV production and characterization.
NATURE BIOMEDICAL ENGINEERING
(2022)
Correction
Engineering, Biomedical
Jessie R. Davis, Xiao Wang, Isaac P. Witte, Tony P. Huang, Jonathan M. Levy, Aditya Raguram, Samagya Banskota, Nabil G. Seidah, Kiran Musunuru, David R. Liu
NATURE BIOMEDICAL ENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Mahshid Malakootian, Parisa Naeli, Seyed Javad Mowla, Nabil G. Seidah
Summary: In this study, the regulatory miRNAs of PCSK7 gene expression were predicted using bioinformatics algorithms. Four miRNAs were identified as potential regulators of PCSK7 expression. The experimental results confirmed the interactions between these miRNAs and PCSK7, and revealed their regulatory effects on PCSK7 expression levels.
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.
Article
Nutrition & Dietetics
Eberhard Windler, Frank-Ulrich Beil, Heiner K. Berthold, Ioanna Gouni-Berthold, Ursula Kassner, Gerald Klose, Stefan Lorkowski, Winfried Maerz, Klaus G. Parhofer, Jogchum Plat, Guenter Silbernagel, Elisabeth Steinhagen-Thiessen, Oliver Weingaertner, Birgit-Christiane Zyriax, Dieter Luetjohann
Summary: Phytosterols (PSs) have been proposed as a dietary means to lower plasma LDL-C. Observational studies show no evidence that plasma PS concentrations would be associated with an increased risk of atherosclerosis or cardiovascular events. PSs offer a dietary approach to cholesterol management based on their LDL-C lowering and absence of adverse safety signals.
Review
Cell Biology
Malak Alannan, Nabil G. G. Seidah, Aksam J. J. Merched
Summary: Metabolic rewiring and defective immune responses play important roles in many cancers. PCSK9, an atypical enzyme, regulates lipid metabolism by controlling LDLR and other cell surface receptors. Studies have also shown its involvement in the immune system and other physiological activities.
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)
Review
Peripheral Vascular Disease
Ioanna Gouni-Berthold, Jonas Schwarz, Heiner K. Berthold
Summary: The treatment of severe hypertriglyceridemia is challenging, and traditional pharmacological options have limited success. Novel therapeutic options targeting APOC3 and ANGPTL3 show promising potential, but the ultimate clinical goal of reducing the risk of acute pancreatitis has not been definitively achieved.
CURRENT ATHEROSCLEROSIS REPORTS
(2023)