Article
Biochemistry & Molecular Biology
Maureen Sampson, Rami A. Ballout, Daniel Soffer, Anna Wolska, Sierra Wilson, Jeff Meeusen, Leslie J. Donato, Erica Fatica, James D. Otvos, Eliot A. Brinton, Robert S. Rosenson, Peter Wilson, Marcelo Amar, Robert Shamburek, Sotirios K. Karathanasis, Alan T. Remaley
Summary: This study developed a new algorithm for classifying lipoprotein disorders based on the standard lipid panel, categorizing patients into classical Fredrickson-like phenotypes and introducing a new hypolipidemic phenotype (Type VI) due to genetic mutations in apoB-metabolism. The validity of the new algorithm was confirmed through lipid analysis by NMR and by concordance with classification by agarose gel electrophoresis/beta-quantification, demonstrating its potential for improving the care of patients at risk for ASCVD.
LIPIDS IN HEALTH AND DISEASE
(2021)
Article
Cardiac & Cardiovascular Systems
Boqun Shi, Hao-Yu Wang, Jinpeng Liu, Zhongxing Cai, Chenxi Song, Lei Jia, Dong Yin, Hongjian Wang, Ke-Fei Dou, Weihua Song
Summary: The study aimed to evaluate whether calculated LDL-C is worse than direct dLDL-C in identifying high-risk patients with coronary artery disease. The study found that misclassification by the Martin/Hopkins and Sampson equations was present in approximately 20% of patients. However, directly measured vs. calculated LDL-C did not identify any more individuals in the PCI population with increased risk of all-cause mortality, recurrent AMI, and MACE, even in high-risk patients such as those with diabetes.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Hematology
Minghao Kou, Ning Ding, Shoshana H. Ballew, Maya J. Salameh, Seth S. Martin, Elizabeth Selvin, Gerardo Heiss, Christie M. Ballantyne, Kunihiro Matsushita, Ron C. Hoogeveen
Summary: Triglyceride-related and HDL-related lipids were independently associated with incident PAD, indicating implications for preventive strategies. Principal component analysis identified three components related to PAD risk.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Medicine, Research & Experimental
Kiran Musunuru
Summary: Currently, statins, ezetimibe, and PCSK9 inhibitors are the standard of care for the prevention and treatment of coronary artery disease, but it remains the leading cause of death worldwide. Many new therapies targeting various lipid traits or inflammation have recently received approval or fared favorably in clinical trials, promising to transform the care of patients at risk for life-threatening coronary events.
ANNUAL REVIEW OF MEDICINE, VOL 72, 2021
(2021)
Article
Cardiac & Cardiovascular Systems
Thomas C. Gilliland, Yuxi Liu, Reza Mohebi, Hannah Miksenas, Sara Haidermota, Megan Wong, Xingdi Hu, Joaquim Rosado Cristino, Auris Browne, Jorge Plutzky, Sotirios Tsimikas, James L. Januzzi Jr, Pradeep Natarajan
Summary: This study investigated the relationships between Lp(a) and OxPLs with angiographic CAD and cardiovascular outcomes. The results showed that Lp(a) and OxPL-apoB were associated with multivessel CAD, and Lp(a), OxPL-apoB, and OxPL-apo(a) were associated with cardiovascular events.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Anna E. Engell, Henrik L. Jorgensen, Bent S. Lind, Anton Pottegard, Christen L. Andersen, John S. Andersen, Margit Kriegbaum, Mia K. Grand, Lise Bathum
Summary: Lipid levels in blood have decreased significantly in the general population due to the use of statins. This trend was observed in primary health care patients who were not using statins from 2001 to 2018, with substantial decreases in total cholesterol and low-density lipoprotein cholesterol levels, especially in the elderly population.
LIPIDS IN HEALTH AND DISEASE
(2021)
Article
Hematology
Wynn G. Hunter, Alexander G. Smith, Rui C. Pinto, Suzanne Saldanha, Anamika Gangwar, Mandana Pahlavani, Sneha Deodhar, John Wilkins, Ambarish Pandey, David Herrington, Philip Greenland, Ioanna Tzoulaki, Anand Rohatgi
Summary: This study investigated the associations between metabolites and cholesterol efflux capacity (CEC) and found independent associations between CEC and the largest-sized particle subclasses of VLDL and HDL, as well as their constituent apolipoproteins and lipids. However, metabolite profiles had poor accuracy in predicting CEC, and race was found to be the most important factor influencing CEC.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Hyungjong Park, Yoonkyung Chang, Heajung Lee, Iksun Hong, Tae-Jin Song
Summary: The study investigates the association between total cholesterol (TC) variability and the occurrence of venous thromboembolism (VTE) using a Korean database. The results show a positive correlation between higher TC variability and the occurrence of VTE, emphasizing the importance of maintaining stable TC levels to prevent VTE.
Review
Pharmacology & Pharmacy
Jelena Vekic, Aleksandra Zeljkovic, Aleksandra Stefanovic, Natasa Bogavac-Stanojevic, Ioannis Ilias, Jose Silva-Nunes, Anca Pantea Stoian, Andrej Janez, Manfredi Rizzo
Summary: There is compelling evidence linking increased levels of low-density lipoprotein cholesterol (LDL-C) to the development of atherosclerotic cardiovascular disease (CVD). However, recent data shows that the majority of patients in Europe are unable to achieve their recommended LDL-C targets. To address this issue, a new approach to lipid-lowering, involving more intensive and earlier intervention, has been proposed for high-risk patients. Additionally, novel lipid biomarkers, such as small dense LDL particles (sdLDL), should be considered as potential therapeutic targets.
Article
Food Science & Technology
Sam Hobson, Henriette de Loor, Karolina Kublickiene, Joachim Beige, Pieter Evenepoel, Peter Stenvinkel, Thomas Ebert
Summary: Patients with kidney failure have a high incidence of cardiovascular disease, partly due to insufficient clearance of uremic toxins. A study found significant inverse associations between lipid profile and different uremic toxins, highlighting the complexity of the uremic milieu.
Review
Biochemistry & Molecular Biology
Brian V. Hong, Jingyuan Zheng, Angela M. Zivkovic
Summary: This review discusses the role of HDL during childhood, pregnancy, and in the elderly, as well as the potential adverse health outcomes associated with disturbances in HDL and knowledge gaps in the role of HDL across these life stages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Andreas Leiherer, Axel Muendlein, Eva Maria Brandtner, Christoph H. Saely, Hana Ramadani, Alexander Vonbank, Arthur Mader, Jorn F. Dopheide, Antti Jylha, Mitja Laaperi, Reijo Laaksonen, Winfried Maerz, Peter Fraunberger, Marcus Kleber, Heinz Drexel
Summary: This study found significant differences in markers of inflammation, ceramide, and phosphatidylcholine levels between PAD and CAD patients, while basic lipid markers did not significantly differ. Ratios and scores derived from ceramides and phosphatidylcholines improved the discrimination between PAD and CAD.
JOURNAL OF INTERNAL MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Sara N. Koenig, Holly C. Sucharski, Elizabeth M. Jose, Emma K. Dudley, Francesca Madiai, Omer Cavus, Aaron D. Argall, Jordan L. Williams, Nathaniel P. Murphy, Caullin B. R. Keith, Mona El Refaey, Richard J. Gumina, Konstantinos D. Boudoulas, M. Wesley Milks, Gbemiga Sofowora, Sakima A. Smith, Thomas J. Hund, Nathan T. Wright, Elisa A. Bradley, Karolina M. Zareba, Loren E. Wold, Ernest L. Mazzaferri, Peter J. Mohler
Summary: Elevated HDL-C is associated with improved cardiovascular outcomes, but clinical trials targeting HDL-C have not been successful. Rare compound heterozygous variants in SCARB1 have been found to cause severe CAD through Mendelian inheritance. These findings support the disease-contributing capability of loss-of-function SCARB1 variants.
CIRCULATION RESEARCH
(2021)
Review
Cell Biology
Manuela Casula, Ornella Colpani, Sining Xie, Alberico L. Catapano, Andrea Baragetti
Summary: Recent studies on the role of high-density lipoprotein cholesterol (HDL-C) in cardiovascular disease have found a complex U-shaped relationship between HDL levels and cardiovascular mortality risk. Additionally, genetic studies, Mendelian randomization approaches, and clinical trials have challenged the traditional notion of a causal link between HDL-C levels and cardiovascular protection.
Article
Biochemistry & Molecular Biology
Tianyu Li, Deshan Yuan, Peizhi Wang, Sida Jia, Ce Zhang, Pei Zhu, Ying Song, Xiaofang Tang, Xueyan Zhao, Zhan Gao, Yuejin Yang, Runlin Gao, Bo Xu, Jinqing Yuan
Summary: ApoB/apoA-1 has better predictive power for total occlusion than non-HDL-c/HDL-c and single lipid measures in patients with established CAD.
LIPIDS IN HEALTH AND DISEASE
(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)
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
Cardiac & Cardiovascular Systems
Jan Boren, Marja-Riitta Taskinen, Elias Bjornson, Chris J. Packard
Summary: Accumulating evidence suggests the causal role of triglyceride-rich lipoproteins and their cholesterol-enriched remnants in atherogenesis. Genetic and kinetic studies have revealed the key proteins involved in the regulation of triglyceride transport and the complexity of triglyceride-rich lipoprotein metabolism. Ongoing investigations aim to understand the consequences of dysregulation caused by diet or genetic variation. The identification of molecular control mechanisms has laid the foundation for precision-medicine approaches to therapy, with novel pharmacological agents targeting specific molecular targets.
NATURE REVIEWS CARDIOLOGY
(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)
Article
Endocrinology & Metabolism
Marja-Riitta Taskinen, Niina Matikainen, Elias Bjornson, Sanni Soderlund, Mari Ainola, Antti Hakkarainen, Nina Lundbom, Carina Sihlbom, Annika Thorsell, Linda Andersson, Martin Adiels, Bolette Hartmann, Carolyn F. Deacon, Jens J. Holst, Chris J. Packard, Jan Boren
Summary: This study aimed to investigate the impact of physiological levels of incretins on chylomicron and VLDL production and clearance rates. The results showed that physiological levels of incretins do not have a significant regulatory effect on lipid metabolism.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(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)
Article
Medicine, Research & Experimental
Marja-Riitta Taskinen, Elias Bjornson, Niina Matikainen, Sanni Soderlund, Joel Ramo, Mari-Mia Ainola, Antti Hakkarainen, Carina Sihlbom, Annika Thorsell, Linda Andersson, Per-Olof Bergh, Marcus Henricsson, Stefano Romeo, Martin Adiels, Samuli Ripatti, Markku Laakso, Chris J. Packard, Jan Boren
Summary: This study investigates the impact of apoC-III on lipoprotein metabolism in individuals with a loss-of-function mutation in the APOC3 gene. The results demonstrate that lowering apoC-III levels significantly affects the metabolism of lipoproteins and remnants, potentially having important implications for cardiovascular disease prevention.
Article
Biochemistry & Molecular Biology
Anna Roubtsova, Damien Garcon, Sandrine Lacoste, Ann Chamberland, Jadwiga Marcinkiewicz, Raphael Metivier, Thibaud Sotin, Martine Paquette, Sophie Bernard, Bertrand Cariou, Cedric Le May, Marlys L. Koschinsky, Nabil G. Seidah, Annik Prat
Summary: The study on PCSK9 knockout mice reveals that female mice shed soluble ectodomain of LDLR massively, while male mice rely on high surface LDLR for replenishment. This shedding process is cholesterol-dependent and influenced by hormone levels in female mice.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2022)
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
Multidisciplinary Sciences
Helena A. K. Lapatto, Minna Kuusela, Aino Heikkinen, Maheswary Muniandy, Birgitta W. van der Kolk, Swetha Gopalakrishnan, Noora Pollanen, Martin Sandvik, Mark S. Schmidt, Sini Heinonen, Sina Saari, Juho Kuula, Antti Hakkarainen, Janne Tampio, Tuure Saarinen, Marja-Riitta Taskinen, Nina Lundbom, Per-Henrik Groop, Marja Tiirola, Pekka Katajisto, Marko Lehtonen, Charles Brenner, Jaakko Kaprio, Satu Pekkala, Miina Ollikainen, Kirsi H. Pietilainen, Eija Pirinen
Summary: Nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD(+)), has shown promise in improving obesity-associated mitochondrial dysfunction and metabolic syndrome. However, short-term clinical trials have not yielded positive results. This study aimed to investigate the long-term effects of NR supplementation on mitochondrial biogenesis and metabolic health in humans. The results showed that NR improved NAD(+) metabolism, muscle mitochondrial number, myoblast differentiation, gut microbiota composition, and epigenetic control of gene expression. However, it did not improve adiposity or metabolic health.
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
Endocrinology & Metabolism
Marja-Riitta Taskinen, Niina Matikainen, Elias Bjornson, Sanni Soderlund, Jussi Inkeri, Antti Hakkarainen, Helka Parviainen, Carina Sihlbom, Annika Thorsell, Linda Andersson, Martin Adiels, Chris J. Packard, Jan Boren
Summary: This study investigated the hypothesis that individuals with type 2 diabetes on statin therapy may have significant abnormalities in the metabolism of intestinally derived lipoproteins. The findings suggest that in these individuals, there are increased production and longer circulation time of ApoB-48-containing lipoproteins, which may contribute to residual cardiovascular disease risk.
Article
Cardiac & Cardiovascular Systems
Elias Bjornson, Martin Adiels, Marja-Riitta Taskinen, Stephen Burgess, Aidin Rawshani, Jan Boren, Chris J. Packard
Summary: In this study, the association between triglyceride-rich lipoproteins (TRL) and coronary heart disease (CHD) was investigated using population data from the UK Biobank. The results suggest that TRL/remnant cholesterol has a stronger and independent association with CHD compared to LDL cholesterol. Moreover, different genetic clusters impact TRL/remnants and LDL differentially, with TRL/remnants exhibiting a higher atherogenicity per particle than LDL.
EUROPEAN HEART JOURNAL
(2023)