Article
Multidisciplinary Sciences
Stephen G. Young, Wenxin Song, Ye Yang, Gabriel Birrane, Haibo Jiang, Anne P. Beigneux, Michael Ploug, Loren G. Fong
Summary: GPIHBP1 is a crucial partner for LPL in lipolytic processing of lipoproteins, stabilizing LPL structure and preserving activity. It captures LPL and shuttles it to the capillary lumen. The AD of GPIHBP1 accelerates LPL binding, preserves LPL activity, and allows LPL to move across ECs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Medicine, Research & Experimental
Shali Jiang, Zhuoqun Ren, Yutao Yang, Qiming Liu, Shenghua Zhou, Yichao Xiao
Summary: GPIHBP1 is a protein anchored by glycosylphosphatidylinositol found in endothelial cells that binds to high-density lipoproteins. It plays a crucial role in transporting and stabilizing lipoprotein lipase, which is vital for lipid metabolism and the marginalization of lipoproteins alongside capillaries. Mutations in the GPIHBP1-LPL complex are central to the onset of chylomicronemia, a condition characterized by high levels of chylomicrons in the blood.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Multidisciplinary Sciences
Wenxin Song, Anne P. Beigneux, Thomas A. Weston, Kai Chen, Ye Yang, Le Phuong Nguyen, Paul Guagliardo, Hyesoo Jung, Anh P. Tran, Yiping Tu, Caitlyn Tran, Gabriel Birrane, Kazuya Miyashita, Katsuyuki Nakajima, Masami Murakami, Peter Tontonoz, Haibo Jiang, Michael Ploug, Loren G. Fong, Stephen G. Young
Summary: This study reveals that the GPIHBP1-transported LPL can detach and move into the EC glycocalyx, where it plays a role in the intravascular processing of triglyceride-rich lipoproteins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cardiac & Cardiovascular Systems
Guenther Silbernagel, Yan Q. Chen, Martin Rief, Marcus E. Kleber, Michael M. Hoffmann, Tatjana Stojakovic, Andreas Stang, Mark A. Sarzynski, Claude Bouchard, Winfried Maerz, Yue-Wei Qian, Hubert Scharnagl, Robert J. Konrad
Summary: Apolipoprotein C-II (ApoC-II) has an inverse J-shaped relationship with cardiovascular mortality, with the lowest risk observed in the middle quintile. Increasing low circulating ApoC-II levels may reduce cardiovascular risk.
EUROPEAN HEART JOURNAL
(2023)
Article
Cardiac & Cardiovascular Systems
Chae Syng Lee, Yajie Zhai, Rui Shang, Trevor Wong, Aurora J. Mattison, Haoning Howard Cen, James D. Johnson, Israel Vlodavsky, Bahira Hussein, Brian Rodrigues
Summary: The study found that flow-induced mechanical forces can increase the release of heparanase from endothelial cells, affecting cardiac metabolism. The release of heparanase is mediated by activation of purinergic receptors and protein kinase D, and is augmented in diabetes.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Nutrition & Dietetics
Ewa Wieczorek, Agnieszka Cwiklinska, Agnieszka Kuchta, Barbara Kortas-Stempak, Anna Gliwinska, Maciej Jankowski
Summary: This study aimed to evaluate the impact of hypercholesterolemia and hypertriglyceridemia on the efficiency of lipoprotein lipase-mediated VLDL-triglyceride lipolysis, as well as the role of HDL in this process. The results showed that VLDL from patients with hypercholesterolemia and hypertriglyceridemia are more resistant to lipolysis, with HDL helping to enhance the efficiency of lipolysis in these groups.
Article
Pharmacology & Pharmacy
Karla Garay-Garcia, Paula Gaete, Carlos O. Mendivil
Summary: This report presents three cases of severe hypertriglyceridemia in adult patients from Quito, Ecuador, all of which were associated with LMF1 gene variants. Two patients presented with acute pancreatitis, while one patient was asymptomatic but had significantly elevated triglyceride levels. The findings suggest that LMF1 gene may be a common cause of severe hypertriglyceridemia in Latin-American patients.
JOURNAL OF CLINICAL LIPIDOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wenlong Yang, Zhengzheng Tan, Shuang Yu, Yuanyuan Ren, Rui Pan, Xiaoyang Yu
Summary: This study proposes an optical fiber sensor based on an enhanced core diameter mismatch for specific recognition and sensitive detection of triglycerides. The sensor achieves higher sensitivity through the excitation of higher-order cladding modes. By immobilizing lipase using covalent binding technology, triglycerides can be hydrolyzed, leading to a shift in the interference dip of the sensor. The sensor exhibits high sensitivity and specificity for triglycerides and holds potential applications in medical research and clinical diagnosis.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2024)
Article
Hematology
Jenni Maatta, Raisa Serpi, Sohvi Horkko, Valerio Izzi, Johanna Myllyharju, Elitsa Y. Dimova, Peppi Koivunen
Summary: The genetic ablation of P4H-TM was shown to protect against atherosclerosis by potentially modulating immuno-metabolic interactions, including the presence of IgM antibodies to Ox-LDL and increased lipoprotein lipase levels. This mechanism could provide a novel approach for intervention in atherosclerosis pathology by targeting hypertriglyceridemia and promoting protective immune responses.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kelli L. Sylvers-Davie, Ashley Segura-Roman, Alicia M. Salvi, Kylie J. Schache, Brandon S. J. Davies
Summary: High plasma TG and low HDL-C levels are risk factors for atherosclerosis and cardiovascular disease, regulated in part by ANGPTL3. This study found that ANGPTL8 is not necessary for EL inhibition, indicating that targeting ANGPTL8 for hypertriglyceridemia or cardiovascular disease may have different outcomes than targeting ANGPTL3.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Marine Hanse, Samina Akbar, Hamed Layeghkhavidaki, Frances T. Yen
Summary: Garcinia cambogia extract (GCE) can lower plasma triglyceride levels and promote weight loss, but may lead to compensatory mechanisms of increased liver and muscle lipids.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Jordan M. Kraaijenhof, Tycho R. Tromp, Nick S. Nurmohamed, Laurens F. Reeskamp, Marije Langenkamp, Johannes H. M. Levels, S. Matthijs Boekholdt, Nicholas J. Wareham, Menno Hoekstra, Erik S. G. Stroes, G. Kees Hovingh, Aldo Grefhorst
Summary: The study found that while ANGPTL3 predominantly resides on HDL, its activity is highest when bound to LDL particles.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Review
Biochemistry & Molecular Biology
Sander Kersten
Summary: Recent literature reviews show that elevated LDL-C and triglycerides are important risk factors for atherosclerotic cardiovascular disease. ANGPTL3 has emerged as a new therapeutic target for lowering plasma LDL-C and triglycerides, with promising results from inactivation of ANGPTL3 through monoclonal antibodies or antisense oligonucleotides in patients with dyslipidemia. Anti-ANGPTL3 therapies offer potential for significantly reducing plasma LDL-C and triglycerides in selected patient groups.
CURRENT OPINION IN LIPIDOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Ira J. Goldberg, Ainara G. Cabodevilla, Dmitri Samovski, Vincenza Cifarelli, Debapriya Basu, Nada A. Abumrad
Summary: Lipoprotein lipase mediates the transfer of lipids to parenchymal cells through or around endothelial cells, controlled at multiple points from synthesis to inhibition. Various pathways, including fatty acid transporter CD36 and other receptors, facilitate the transit of lipids into muscle and adipose tissues. Endothelial cells play a crucial role in lipid delivery, but there are still aspects of this process that require further investigation.
Review
Peripheral Vascular Disease
Farzahna Mohamed, Brett S. Mansfield, Frederick J. Raal
Summary: This article discusses the role of ANGPTL3 in lipoprotein metabolism and the efficacy of evinacumab, an ANGPTL3 inhibitor, in reducing LDL-C. Pharmacological inactivation of ANGPTL3 significantly lowers LDL-C, and holds promise for further reducing ASCVD risk.
CURRENT ATHEROSCLEROSIS REPORTS
(2022)
Article
Cardiac & Cardiovascular Systems
Fulong Wang, Thomas Pulinilkunnil, Stephane Flibotte, Corey Nislow, Israel Vlodaysky, Bahira Hussein, Brian Rodrigues
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2019)
Article
Cardiac & Cardiovascular Systems
Karanjit Puri, Nathaniel Lal, Rui Shang, Sanjoy Ghosh, Stephane Flibotte, Roger Dyer, Bahira Hussein, Brian Rodrigues
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2019)
Article
Biochemistry & Molecular Biology
Purvi C. Trivedi, Jordan J. Bartlett, Angella Mercer, Logan Slade, Marc Surette, Andrea Ballabio, Stephane Flibotte, Bahira Hussein, Brian Rodrigues, Petra C. Kienesberger, Thomas Pulinilkunnil
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2020)
Article
Cardiac & Cardiovascular Systems
Matthieu Ruiz, Maya Khairallah, Dharmendra Dingar, George Vaniotis, Ramzi J. Khairallah, Benjamin Lauzier, Simon Thibault, Joelle Trepanier, Yanfen Shi, Annie Douillette, Bahira Hussein, Sherin Ali Nawaito, Pramod Sahadevan, Albert Nguyen, Fatiha Sahmi, Marc-Antoine Gillis, Martin G. Sirois, Matthias Gaestel, William C. Stanley, Celine Fiset, Jean-Claude Tardif, Bruce G. Allen
Summary: The study showed that MK2(-/-) mice exhibited signs of possible early diastolic dysfunction at 12 weeks of age; they also had lower body temperature, decreased body weight, and altered expression of certain metabolic genes.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Cell Biology
Aurore Claude-Taupin, Jingyue Jia, Zambarlal Bhujabal, Meriem Garfa-Traore, Suresh Kumar, Gustavo Peixoto Duarte da Silva, Ruheena Javed, Yuexi Gu, Lee Allers, Ryan Peters, Fulong Wang, Luciana Jesus da Costa, Sandeep Pallikkuth, Keith A. Lidke, Mario Mauthe, Pauline Verlhac, Yasuo Uchiyama, Michelle Salemi, Brett Phinney, Sharon A. Tooze, Muriel C. Mari, Terje Johansen, Fulvio Reggiori, Vojo Deretic
Summary: ATG9A plays a crucial role in autophagy, organizing components of the ESCRT system with IQGAP1 to protect the plasma membrane from damage in various biological contexts.
NATURE CELL BIOLOGY
(2021)
Article
Endocrinology & Metabolism
Rui Shang, Nathaniel Lal, Chae Syng Lee, Yajie Zhai, Karanjit Puri, Oscar Seira, Robert C. Boushel, Ibrahim Sultan, Markus Rasanen, Kari Alitalo, Bahira Hussein, Brian Rodrigues
Summary: The study demonstrates that VEGFB has a significant impact on cardiac metabolism by lowering LPL activity and preventing lipid metabolite accumulation, improving insulin action. This suggests that VEGFB could be a potential cardioprotective therapy for treating metabolic disorders.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Haoning Howard Cen, Bahira Hussein, Jose Diego Botezelli, Su Wang, Jiashuo Aaron Zhang, Nilou Noursadeghi, Niels Jessen, Brian Rodrigues, James A. Timmons, James D. Johnson
Summary: Hyperinsulinemia, often considered as a compensatory response to insulin resistance, may actually contribute to insulin resistance. The molecular mechanisms underlying this cyclic process are poorly understood. This study found a reliable negative correlation between fasting insulin and INSR mRNA in skeletal muscle. Through cell culture experiments, it was demonstrated that elevated insulin levels attenuated AKT and ERK signaling in muscle cells. RNA-sequencing analysis revealed changes in gene expression related to insulin receptor signaling, FOXO signaling, and glucose metabolism pathways. Hyperinsulinemia led to reduced Insr gene expression and decreased surface INSR protein. SIN3A was identified as a negative regulator of Insr mRNA. These findings provide insights into the mechanisms of hyperinsulinemia-induced insulin resistance in muscle.
Article
Cell Biology
Jingyue Jia, Fulong Wang, Zambarlal Bhujabal, Ryan Peters, Michal Mudd, Thabata Duque, Lee Allers, Ruheena Javed, Michelle Salemi, Christian Behrends, Brett Phinney, Terje Johansen, Vojo Deretic
Summary: Lysosomal damage induces the formation of stress granules and coordinates mTOR inactivation through the process of membrane atg8ylation. This process is effective against various lysosomal damaging agents.
JOURNAL OF CELL BIOLOGY
(2022)
Editorial Material
Cell Biology
Jingyue Jia, Fulong Wang, Zambarlal Bhujabal, Ryan Peters, Michal Mudd, Thabata Duque, Lee Allers, Ruheena Javed, Michelle Salemi, Christian Behrends, Brett Phinney, Terje Johansen, Vojo Deretic
Summary: The functions of mammalian Atg8 proteins (mATG8s) go beyond autophagy and also include Atg8ylation. Lysosomal damage induces stress granules (SGs) that inhibit protein translation via EIF2A/eIF2 alpha phosphorylation and promote ATF4-dependent stress response. GABARAPs interact with NUFIP2 and G3BP1, and Atg8ylation is required for their recruitment to damaged lysosomes. The roles of NUFIP2 and G3BP1 in SG formation and MTOR activation are regulated by GABARAP and Atg8ylation.
Article
Cardiac & Cardiovascular Systems
Chae Syng Lee, Yajie Zhai, Rui Shang, Trevor Wong, Aurora J. Mattison, Haoning Howard Cen, James D. Johnson, Israel Vlodavsky, Bahira Hussein, Brian Rodrigues
Summary: The study found that flow-induced mechanical forces can increase the release of heparanase from endothelial cells, affecting cardiac metabolism. The release of heparanase is mediated by activation of purinergic receptors and protein kinase D, and is augmented in diabetes.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Cell Biology
Fulong Wang, Ryan Peters, Jingyue Jia, Michal Mudd, Michelle Salemi, Lee Allers, Ruheena Javed, Thabata L. A. Duque, Masroor A. Paddar, Einar S. Trosdal, Brett Phinney, Vojo Deretic
Summary: ATG5 is involved in the lipidation of ATG8 proteins, essential for membrane atg8ylation and autophagy. Loss of Atg5 in myeloid cells leads to early mortality in tuberculosis models. Absence of ATG5 promotes lysosomal exocytosis, secretion of extracellular vesicles, and excessive degranulation in neutrophils. This is due to lysosomal disrepair and sequestration of ALIX by an alternative conjugation complex, highlighting the importance of ATG5 in host protection and the branching aspects of atg8ylation beyond autophagy.
DEVELOPMENTAL CELL
(2023)
Article
Biochemistry & Molecular Biology
Ruheena Javed, Ashish Jain, Thabata Duque, Emily Hendrix, Masroor Ahmad Paddar, Sajjad Khan, Aurore Claude-Taupin, Jingyue Jia, Lee Allers, Fulong Wang, Michal Mudd, Graham Timmins, Keith Lidke, Tor Erik Rusten, Prithvi Reddy Akepati, Yi He, Fulvio Reggiori, Eeva-Liisa Eskelinen, Vojo Deretic
Summary: This study reveals that autophagosomal membranes become permeable and fail to mature into autolysosomes in cells lacking principal ATG8 proteins (mATG8s). It further uncovers a previously unknown function of mATG8s in maintaining the sealed state of autophagosomal membranes. The binding of mATG8 proteins GABARAP and LC3A to key ESCRT-I components contributes to the integrity and impermeability of autophagic membranes.
Editorial Material
Microbiology
Vojo Deretic, Fulong Wang
Summary: Autophagy re-emerges as a central player in controlling Mycobacterium tuberculosis in macrophages, as demonstrated in murine models and human cells.
NATURE MICROBIOLOGY
(2023)
Article
Cell Biology
Fulong Wang, Einar S. Trosdal, Masroor Ahmad Paddar, Thabata L. A. Duque, Lee Allers, Michal Mudd, Prithvi R. Akepati, Ruheena Javed, Jingyue Jia, Michelle Salemi, Brett Phinney, Vojo Deretic
Summary: ATG5 plays a crucial role in membrane Atg8ylation and has negative effects on tuberculosis in myeloid cells. The absence of ATG5 leads to a lysosomal hypersensitivity phenotype in endolysosomal organelles, partially due to compromised recruitment of ESCRT proteins for lysosomal repair. This finding is of significance for understanding tuberculosis pathogenesis.