Article
Cardiac & Cardiovascular Systems
Tahir Mahmood, Jessica Minnier, Matthew K. Ito, Qian H. Li, Andrew Koren, Ivy W. Kam, Sergio Fazio, Michael D. Shapiro
Summary: This study aimed to investigate the prevalence of discordant plasma LDL-C/Lp(a) response to the PCSK9 inhibitor alirocumab, and a high prevalence of discordant response was observed, suggesting that alirocumab may reduce Lp(a) through alternative pathways.
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Gregory G. Schwartz, Michael Szarek, Vera A. Bittner, Rafael Diaz, Shaun G. Goodman, J. Wouter Jukema, Ulf Landmesser, Patricio Lopez-Jaramillo, Garen Manvelian, Robert Pordy, Michel Scemama, Peter R. Sinnaeve, Harvey D. White, Ph Gabriel Steg
Summary: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Douglas G. Johns, Louis-Charles Campeau, Puja Banka, An Bautmans, Tjerk Bueters, Elisabetta Bianchi, Danila Branca, Paul G. Bulger, Inne Crevecoeur, Fa-Xiang Ding, Robert M. Garbaccio, Erik D. Guetschow, Yan Guo, Sookhee N. Ha, Jennifer M. Johnston, Hubert Josien, Eunkyung A. Kauh, Kenneth A. Koeplinger, Jeffrey T. Kuethe, Eseng Lai, Christine L. Lanning, Anita Y. H. Lee, Li Li, Anilkumar G. Nair, Edward A. O'Neill, S. Aubrey Stoch, David A. Thaisrivongs, Thomas J. Tucker, Petr Vachal, Kristien van Dyck, Frederic P. Vanhoutte, Bram Volckaert, Dennis G. Wolford, Andy Xu, Tian Zhao, Dan Zhou, Susan Zhou, Xiaohong Zhu, Hratch J. Zokian, Abbas M. Walji, Harold B. Wood
Summary: Through structure-based drug design and novel synthetic chemistry, an oral PCSK9 inhibitor MK-0616 was developed and validated in clinical trials for its effectiveness in lowering cholesterol.
Article
Pharmacology & Pharmacy
Enchen Zhou, Zhuang Li, Hiroyuki Nakashima, Ahlam Choukoud, Sander Kooijman, Jimmy F. P. Berbee, Patrick C. N. Rensen, Yanan Wang
Summary: Accelerating lipolytic processing of VLDL by brown fat activation can further lower (V)LDL levels and reduce the risk of atherosclerosis.
PHARMACOLOGICAL RESEARCH
(2021)
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)
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.
Article
Medicine, General & Internal
Maciej Banach, Jose Luis Lopez-Sendon, Maurizio Averna, Bertrand Cariou, Megan Loy, Garen Manvelian, Isabela Batsu, Yann Poulouin, Daniel Gaudet
Summary: The study evaluated the real-life effectiveness of alirocumab treatment in high cardiovascular risk patients. The results showed that alirocumab treatment significantly reduced LDL-C levels in different statin intensity subgroups and prior ezetimibe therapy subgroups, with high patient adherence.
ARCHIVES OF MEDICAL SCIENCE
(2022)
Article
Endocrinology & Metabolism
Jonas Ghouse, Gustav Ahlberg, Henning Bundgaard, Morten S. Olesen
Summary: This study evaluated the association between PCSK9 predicted loss-of-function (pLoF) variants and glycemic traits, hepatobiliary function, and neurocognitive traits. The results showed significant effects of PCSK9 pLoF variants on lipid and lipoprotein metabolism, but no significant associations with glycemic traits, hepatobiliary function, and neurocognitive traits.
Article
Biochemistry & Molecular Biology
Lung-An Hsu, Ming-Sheng Teng, Semon Wu, Hsin-Hua Chou, Yu-Lin Ko
Summary: The study found that PCSK9 is linked to LDL-C levels and the risk of diabetes, with common and rare variants of PCSK9 showing significant associations with LDL-C levels and diabetes risk. Mendelian randomization analysis revealed an inverse association between LDL-C levels and diabetes mellitus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Jamal S. Rana, Salim S. Virani, Howard H. Moffet, Jennifer Y. Liu, Landis A. Coghlan, Jitesh Vasadia, Christie M. Ballantyne, Andrew J. Karter
Summary: The study aimed to evaluate the association between outpatient LDL-C testing and subsequent statin adherence and intensification in patients after an ASCVD event. The results showed that LDL-C testing was associated with improved statin adherence and higher rates of treatment intensification.
AMERICAN JOURNAL OF MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Aya Egbaria, Walid Saliba, Barak Zafrir
Summary: The study compared the LDL-C estimation between Friedewald and Martin/Hopkins methods in high-risk patients achieving low LDL-C under PCSK9i treatment. Results showed that the Martin/Hopkins method had a higher proportion of upward discordance in LDL-C estimation, particularly in patients with elevated triglycerides.
CARDIOVASCULAR DRUGS AND THERAPY
(2021)
Article
Cardiac & Cardiovascular Systems
Christie M. Ballantyne, Puja Banka, Gustavo Mendez, Raymundo Garcia, Julio Rosenstock, Anthony Rodgers, Geraldine Mendizabal, Yale Mitchel, Alberico L. Catapano
Summary: MK-0616, an oral PCSK9 inhibitor, effectively reduces LDL-C levels and is well tolerated in the treatment of hypercholesterolemia according to a Phase 2b clinical trial.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Rui Gao, Kaixin Du, Jinhua Liang, Yi Xia, Jiazhu Wu, Yue Li, Bihui Pan, Li Wang, Jianyong Li, Wei Xu
Summary: This study aims to evaluate the prognostic value of cholesterol levels in CLL and develop a prognostic nomogram that incorporates lipid metabolism. The results showed that lower cholesterol levels at diagnosis were associated with worse prognosis, and post-therapeutic elevation of cholesterol levels correlated with better survival. Therefore, cholesterol profiles can be used as a cheap and readily accessible tool for predicting prognosis in CLL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Chin-Huan Chang, Shu-Tin Yeh, Seng-Wei Ooi, Chung-Yi Li, Hua-Fen Chen
Summary: This study determined the optimal levels of LDL-C in patients with type 2 diabetes and found U-shaped associations between lower and higher mean LDL-C levels and all-cause and cardiovascular mortality. The study also found that in patients using statin medications, both lower and higher levels of LDL-C were associated with increased risks of all-cause and cardiovascular mortality.
Article
Biochemistry & Molecular Biology
Xin Zhao, Jianbin Sun, Sixu Xin, Xiaomei Zhang
Summary: This study analyzed the association between blood lipid metabolism and osteoporosis (OP) in older adults with type 2 diabetes mellitus (T2DM). The results showed that higher levels of low-density lipoprotein cholesterol (LDL-C) were associated with OP, while higher levels of high-density lipoprotein cholesterol (HDL-C) were associated with non-osteoporotic patients. Age, parathyroid hormone (PTH), total cholesterol (TC), and LDL-C were negatively linked to bone mineral density (BMD), while body mass index (BMI), uric acid (UA) level, HDL-C level, and glomerular filtration rate (eGFR) were positively related to BMD. In postmenopausal women, raised LDL-C was an independent risk factor for OP, while raised HDL-C was protective. Conclusion: Blood lipid levels are related to sex in older T2DM patients, with HDL-C being a protective factor for OP in both men and women, and LDL-C being a predictor for OP in postmenopausal women.
Review
Pathology
Valentin Blanchard, Ilya Khantalin, Stephane Ramin-Mangata, Kevin Chemello, Brice Nativel, Gilles Lambert
Article
Hematology
Mikael Croyal, Valentin Blanchard, Khadija Ouguerram, Maud Chetiveaux, Lea Cabioch, Thomas Moyon, Stephanie Billon-Crossouard, Audrey Aguesse, Karine Bernardeau, Cedric Le May, Laurent Flet, Gilles Lambert, Samy Hadjadj, Bertrand Cariou, Michel Krempf, Estelle Nobecourt-Dupuy
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Benny J. Evison, James T. Palmer, Gilles Lambert, Herbert Treutlein, Jun Zeng, Brice Nativel, Kevin Chemello, Qing Zhu, Jie Wang, Yanfen Teng, Wei Tang, Yanfeng Xu, Anuj Kumar Rathi, Sanjay Kumar, Alexandra K. Suchowerska, Jasneet Parmar, Ian Dixon, Graham E. Kelly, James Bonnar
BIOORGANIC & MEDICINAL CHEMISTRY
(2020)
Article
Medicine, General & Internal
Nadine Leonie de Boer, Alexandra R. M. Brandt-Kerkhof, Eva V. E. Madsen, Marjolein Diepeveen, Esther van Meerten, Ruben A. G. van Eerden, Femke M. de Man, Rachida Bouamar, Stijn L. W. Koolen, Ignace H. J. T. de Hingh, Checca Bakkers, Koen P. Rovers, Geert-Jan M. Creemers, Maarten J. Deenen, Onno W. Kranenburg, Alexander Constantinides, Ron H. J. Mathijssen, Cornelis Verhoef, Jacobus W. A. Burger
Article
Pathology
Iris Van't Erve, Koen P. Rovers, Alexander Constantinides, Karen Bolhuis, Emma C. E. Wassenaar, Robin J. Lurvink, Clement J. Huysentruyt, Petur Snaebjornsson, Djamila Boerma, Daan van den Broek, Tineke E. Buffart, Max J. Lahaye, Arend G. J. Aalbers, Niels F. M. Kok, Gerrit A. Meijer, Cornelis J. A. Punt, Onno Kranenburg, Ignace H. J. T. de Hingh, Remond J. A. Fijneman
Summary: The study found that tumor-derived cfDNA in plasma is not a suitable biomarker for monitoring peritoneal metastases in colorectal cancer patients, while detection of cfDNA in peritoneal fluid may offer an alternative for guiding treatment decisions in peritoneal metastases.
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
(2021)
Article
Medicine, General & Internal
Robin J. Lurvink, Paulien Rauwerdink, Koen P. Rovers, Emma C. E. Wassenaar, Maarten J. Deenen, Joost Nederend, Clement J. R. Huysentruyt, Iris van 't Erve, Remond J. A. Fijneman, Erik J. R. J. van der Hoeven, Cornelis A. Seldenrijk, Alexander Constantinides, Onno Kranenburg, Maartje Los, Karin H. Herbschleb, Anna M. J. Thijs, Geert-Jan M. Creemers, Jacobus W. A. Burger, Marinus J. Wiezer, Simon W. Nienhuijs, Djamila Boerma, Ignace H. J. T. de Hingh
Summary: This study aims to evaluate the safety, feasibility, antitumour activity, patient-reported outcomes, costs, and pharmacokinetics of first-line bidirectional therapy in patients with isolated unresectable colorectal peritoneal metastases. The primary outcome is the occurrence of grade >= 3 adverse events, and key secondary outcomes include treatment-related characteristics, tumour response, patient-reported outcomes, systemic pharmacokinetics, costs, progression-free survival, and overall survival.
Editorial Material
Cardiac & Cardiovascular Systems
Kevin Chemello, Ali K. Jaafar, Gilles Lambert
EUROPEAN HEART JOURNAL
(2021)
Letter
Clinical Neurology
Brice Nativel, Stephane Ramin-Mangata, David Couret, Cynthia Planesse, Mathias Roche, Antonio Gallo, Olivier Meilhac, Gilles Lambert, Steeve Bourane
Article
Biochemistry & Molecular Biology
Kepa B. Uribe, Kevin Chemello, Asier Larrea-Sebal, Asier Benito-Vicente, Unai Galicia-Garcia, Steeve Bourane, Ali K. Jaafar, Gilles Lambert, Cesar Martin
Summary: Research shows that GOF mutations of the PCS9 gene lead to familial hypercholesterolemia, while LOF mutations are associated with reduced cholesterol levels. By studying the effects of different PCS9 variants on LDLR expression and affinity through transient transfections of HEK293 and HepG2 cells, it is possible to reliably determine their GOF or LOF status.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Peripheral Vascular Disease
Kevin Chemello, Dirk J. Blom, A. David Marais, Gilles Lambert, Valentin Blanchard
Summary: Lp(a) is a highly atherogenic lipoprotein species with strong genetic determination of its concentration. The APOE gene, in addition to the LPA gene, plays an important role in modulating Lp(a) concentrations. Carriers of the APOE2 variant display lower Lp(a) levels, but this does not significantly affect circulating Lp(a). Mechanistically, apoE appears to affect the production, but not the catabolism, of Lp(a).
CURRENT ATHEROSCLEROSIS REPORTS
(2022)
Article
Cardiac & Cardiovascular Systems
Florian Kronenberg, Samia Mora, Erik S. G. Stroes, Brian A. Ference, Benoit J. Arsenault, Lars Berglund, Marc R. Dweck, Marlys Koschinsky, Gilles Lambert, Francois Mach, Catherine J. McNeal, Patrick M. Moriarty, Pradeep Natarajan, Borge G. Nordestgaard, Klaus G. Parhofer, Salim S. Virani, Arnold von Eckardstein, Gerald F. Watts, Jane K. Stock, Kausik K. Ray, Lale S. Tokgozoglu, Alberico L. Catapano
Summary: This consensus statement provides updated evidence on the role of Lp(a) in ASCVD and aortic valve stenosis, and offers clinical guidance on testing and treating elevated Lp(a) levels.
EUROPEAN HEART JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Alexandra K. Suchowerska, Geurt Stokman, James T. Palmer, Phillip A. Coghlan, Elsbet J. Pieterman, Nanda Keijzer, Gilles Lambert, Kevin Chemello, Ali K. Jaafar, Jasneet Parmar, Liping Yan, Yingtao Tong, Lin Mu, Hans M. G. Princen, James Bonnar, Benny J. Evison
Summary: This study reported the discovery of an orally bioavailable small-molecule inhibitor of PCSK9 called NYX-PCSK9i, which demonstrated significant cholesterol-lowering activity in hyperlipidemic APOE*3-Leiden.CETP mice. NYX-PCSK9i has the potential to be a new therapy for hypercholesterolemia and can enhance the lipid-lowering activities of statins.
JOURNAL OF LIPID RESEARCH
(2022)
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)
Article
Cardiac & Cardiovascular Systems
Kevin Chemello, Sandra Beeske, Thi Thu Trang Tran, Valentin Blanchard, Elise F. Villard, Bruno Poirier, Jean-Christophe Le Bail, Gihad Dargazanli, Sophie Ho-Van-Guimbal, Denis Boulay, Olivier Bergis, Marie-Pierre Pruniaux, Mikael Croyal, Philip Janiak, Etienne Guillot, Gilles Lambert
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2020)
Letter
Cardiac & Cardiovascular Systems
Valentin Blanchard, Mikael Croyal, Ilya Khantalin, Stephane Ramin-Mangata, Kevin Chemello, Brice Nativel, Dirk. J. Blom, A. David Marais, Gilles Lambert
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2019)
Article
Medicine, Research & Experimental
Bincy Varghese, Sreeranjini Babu, Aishwarya Jala, Panchanan Das, Rajesh Raju, Roshan M. Borkar, Ramu Adela
Summary: Through integrating next-generation sequencing and metabolomics multi-omics analysis of placenta, this study identified differentially expressed miRNAs, their target genes, altered metabolites, and metabolic pathways in gestational hypertension (GH) patients. The findings obtained from this study may contribute to further understanding of the molecular pathways associated with GH and the evaluation of prognostic markers.
ARCHIVES OF MEDICAL RESEARCH
(2024)