Article
Hematology
Masato Sasaki, Mina Delawary, Hidetaka Sakurai, Hideki Kobayashi, Naoki Nakao, Hiromi Tsuru, Yumiko Fukushima, Shoko Honzumi, Sachiko Moriyama, Naoya Wada, Toshio Kaneko, Keisuke Yamada, Naoki Terasaka, Kazuishi Kubota
Summary: The study explores the potential of DS-8190a as a novel therapeutic for atherosclerosis, showing its ability to increase HDL cholesterol levels and reduce atherosclerotic lesion area in monkeys and rodent models.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jihong Lian, Jelske N. van der Veen, Russell Watts, Rene L. Jacobs, Richard Lehner
Summary: This study investigated the role of hepatic Ces1d in cholesterol homeostasis using liver-specific Ces1d-deficient mice. The findings indicated that the absence of Ces1d did not affect RCT flux or cause additional liver CE accumulation after a high-cholesterol diet challenge, challenging the importance of Ces1d as a major hepatic CE hydrolase.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Cell Biology
Gaetana Napolitano, Gianluca Fasciolo, Maria Teresa Muscari Tomajoli, Alessandro Carlucci, Ester Ascione, Alfonso Salvatore
Summary: High-density lipoprotein (HDL) is an anti-atherosclerotic protein that converts cholesterol into ester form and transports excess cholesterol to the liver. However, when HDL undergoes oxidation, it becomes dysfunctional and contributes to the development of atherosclerosis. In this study, we found that superoxide radicals, produced during early atherosclerosis, directly oxidize HDL and impair the function of its protein component ApoA1. These findings provide insights into the potential mechanism of atherosclerosis development and suggest therapeutic approaches targeting superoxide generation.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Yasuhiro Endo, Masanori Fujita, Katsunori Ikewaki
Summary: Cardiovascular disease (CVD) is the leading cause of death in Western countries. Recent epidemiology studies have shown a U-shaped relationship between high-density lipoprotein cholesterol (HDL-C) levels and CVD mortality, with increased mortality in patients with extremely high HDL-C levels. HDL-C raising therapy using nicotinic acids or CETP inhibitors has shown limited efficacy in reducing CVD events. As a result, the focus has shifted to evaluating HDL functionality as a novel biomarker for CVD risk. This review provides an overview of the current status and future perspectives on HDL functions, based on findings from basic research and clinical trials.
Review
Biochemistry & Molecular Biology
Cecilia Vitali, Daniel J. Rader, Marina Cuchel
Summary: The review summarizes the rare genetic lecithin:cholesterol acyltransferase (LCAT) deficiency, which presents as two different syndromes: Familial LCAT deficiency (FLD) and Fish-eye disease (FED). FLD is characterized by low HDL-C, corneal opacity, anaemia, and renal disease. The review discusses the recent advances in potential therapeutics for FLD, including LCAT activators and HDL mimetics, and emphasizes the need for identifying efficacy endpoints and personalized treatments based on the clinical characteristics of individual patients.
CURRENT OPINION IN LIPIDOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Marc P. Bonaca, Richard T. George, David A. Morrow, Brian A. Bergmark, Jeong-Gun Park, Liron Abuhatzira, Andrea L. Vavere, Sotirios K. Karathanasis, ChaoYu Jin, Dewei She, Boaz Hirshberg, Judy Hsia, Marc S. Sabatine
Summary: The study demonstrated that multiple ascending doses of MEDI6012 were safe and well tolerated, and significantly increased HDL-C, HDL cholesteryl ester, and total cholesteryl ester levels in a dose-related manner. These findings support the ongoing Phase 2b program investigating MEDI6012 in ST-elevation MI.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Olivier Kamtchueng Simo, Hicham Berrougui, Tamas Fulop, Abdelouahed Khalil
Summary: Aging may reduce the ability of HDL to mediate reverse cholesterol transport, while an atherogenic diet can enhance this process. Cholesterol accumulation in the aortas is more pronounced in aged mice, exacerbating susceptibility to diet-induced atherosclerosis. The dysregulation of membrane cholesterol transporters' expression levels contributes to this phenomenon.
Article
Medicine, General & Internal
Jacob J. Christensen, Ingunn Narverud, Maija Ruuth, Martin Heier, Matti Jauhiainen, Stine M. Ulven, Martin P. Bogsrud, Petri T. Kovanen, Bente Halvorsen, Michael N. Oda, Cecilie Wium, Kjetil Retterstol, Katariina oorni, Kirsten B. Holven
Summary: Children with familial hypercholesterolemia (FH) were found to have disrupted lipoprotein functions, with increased atherogenicity of LDL and disturbed HDL function. These alterations provide further understanding of the risk for atherosclerotic cardiovascular disease in FH children.
JOURNAL OF INTERNAL MEDICINE
(2021)
Review
Nutrition & Dietetics
Bianca Papotti, Joan Carles Escola-Gil, Josep Julve, Francesco Poti, Ilaria Zanotti
Summary: Reverse cholesterol transport is a physiological mechanism that protects cells from excessive cholesterol accumulation, while dietary lipids may have detrimental effects on cardiovascular health. This review summarizes the mechanisms of action of different types of dietary lipids on various steps of RCT and provides a critical analysis of data from experimental models to clarify their effects on cardiovascular disease.
Article
Medicine, Research & Experimental
Laura Giorgi, Akseli Niemela, Esa-Pekka Kumpula, Ossi Natri, Petteri Parkkila, Juha T. Huiskonen, Artturi Koivuniemi
Summary: This study combines coarse-grained molecular dynamics simulations with complementary experiments to gain mechanistic insight into how apoA-I mimetic peptide 22A and its variants tune LCAT activity in peptide-lipid nanodiscs. Results show that peptide 22A forms transient antiparallel dimers at the rim of nanodiscs, and the removal of C-terminal lysine K22 decreases dimerization tendency and LCAT activity. Furthermore, simulations reveal that LCAT localizes preferentially to the rim of nanodiscs in a manner that shields important domains from water phase, and the conformation of LCAT in the rim affects its activity.
MOLECULAR PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Ilaria Zanotti, Francesco Poti, Marina Cuchel
Summary: HDL plays an antiatherogenic role by accepting cholesterol from cells and promoting reverse cholesterol transport, with cholesterol efflux capacity being associated with cardiovascular risk in various human cohorts. These findings support the protective role of RCT in humans.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2022)
Review
Nutrition & Dietetics
Malgorzata Sidorkiewicz
Summary: The maintenance of cholesterol homeostasis involves complicated processes such as regulation of cholesterol synthesis, dietary uptake, and bile acid synthesis and excretion. Reverse cholesterol transport, mediated by high-density lipoproteins, plays a vital role in transferring cholesterol from non-hepatic cells to the liver for excretion. MicroRNA-33 has been identified as a key regulator of cholesterol homeostasis, impacting both cellular cholesterol efflux and bile metabolism in the liver. Understanding these mechanisms could lead to new perspectives in microRNA-targeted treatment for cholesterol imbalance.
Review
Biochemistry & Molecular Biology
Cecilia Vitali, Archna Bajaj, Christina Nguyen, Jill Schnall, Jinbo Chen, Kostas Stylianou, Daniel J. Rader, Marina Cuchel
Summary: This article systematically reviews the natural history and biomarkers of LCAT deficiency in order to guide the development of novel therapeutics. The study found that fish-eye disease and familial LCAT deficiency are characterized by early corneal opacity and markedly reduced HDL-C levels. In familial LCAT deficiency, proteinuria/hematuria are the first signs of renal impairment, followed by rapid decline of renal function. LCAT activity and the percentage of circulating esterified cholesterol (EC%) are the best discriminators between these two syndromes.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Weila Dong, Karen H. Y. Wong, Youbin Liu, Michal Levy-Sakin, Wei-Chien Hung, Mo Li, Boyang Li, Sheng Chih Jin, Jungmin Choi, Francesc Lopez-Giraldez, Dedeepya Vaka, Annie Poon, Catherine Chu, Richard Lao, Melek Balamir, Irina Movsesyan, Mary J. Malloy, Hongyu Zhao, Pui-Yan Kwok, John P. Kane, Richard P. Lifton, Clive R. Pullinger
Summary: Low levels of HDL-C are associated with increased risk of arteriosclerotic coronary heart disease, and this study found damaging rare variants in the ABCA1 and LDLR genes to be particularly high in individuals with low HDL-C. Numerous damaging variants were also identified in other HDL candidate genes, suggesting a potential new area of interest in HDL genomics.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Johanna F. Schachtl-Riess, Stefan Coassin, Claudia Lamina, Egon Demetz, Gertraud Streiter, Richard Hilbe, Florian Kronenberg
Summary: The study found that the per-well method for measuring CEC had lower rejection rates and coefficients of variation compared to the time zero method, and the use of four controls on each plate improved assay performance for both methods. Additionally, the choice of lysis reagents, cell numbers, and assay setup significantly impact the quality and reliability of CEC quantification.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Ricquita D. Pollard, Brian Fulp, Mary G. Sorci-Thomas, Michael J. Thomas
Article
Cardiac & Cardiovascular Systems
Mary G. Sorci-Thomas, Michael J. Thomas
CIRCULATION RESEARCH
(2016)
Article
Medicine, Research & Experimental
Hsin-Yuan Cheng, Dalia E. Gaddis, Runpei Wu, Chantel McSkimming, LaTeira D. Haynes, Angela M. Taylor, Coleen A. McNamara, Mary Sorci-Thomas, Catherine C. Hedrick
JOURNAL OF CLINICAL INVESTIGATION
(2016)
Article
Biochemistry & Molecular Biology
Mi-Hye Lee, Kathryn M. Appleton, Hesham M. El-Shewy, Mary G. Sorci-Thomas, Michael J. Thomas, Maria F. Lopes-Virella, Louis M. Luttrell, Samar M. Hammad, Richard L. Klein
JOURNAL OF LIPID RESEARCH
(2017)
Article
Cardiac & Cardiovascular Systems
Sushma Kaul, Hao Xu, Manal Zabalawi, Elisa Maruko, Brian E. Fulp, Theresa Bluemn, Kristina L. Brzoza-Lewis, Mark Gerelus, Ranjuna Weerasekera, Rachel Kallinger, Roland James, Yi (Sherry) Zhang, Michael J. Thomas, Mary G. Sorci-Thomas
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2016)
Editorial Material
Biochemistry & Molecular Biology
Mary G. Sorci-Thomas, Michael J. Thomas
JOURNAL OF LIPID RESEARCH
(2017)
Article
Biochemistry & Molecular Biology
John T. Melchior, Ryan G. Walker, Allison L. Cooke, Jamie Morris, Mark Castleberry, Thomas B. Thompson, Martin K. Jones, Hyun D. Song, Kerry-Anne Rye, Michael N. Oda, Mary G. Sorci-Thomas, Michael J. Thomas, Jay W. Heinecke, Xiaohu Mei, David Atkinson, Jere P. Segrest, Sissel Lund-Katz, Michael C. Phillips, W. Sean Davidson
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
John T. Melchior, Ryan G. Walker, Allison L. Cooke, Jamie Morris, Mark Castleberry, Thomas B. Thompson, Martin K. Jones, Hyun D. Song, Kerry-Anne Rye, Michael N. Oda, Mary G. Sorci-Thomas, Michael J. Thomas, Jay W. Heinecke, Xiaohu Mei, David Atkinson, Jere P. Segrest, Sissel Lund-Katz, Michael C. Phillips, W. Sean Davidson
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2017)
Review
Biochemistry & Molecular Biology
Amber B. Ouweneel, Michael J. Thomas, Mary G. Sorci-Thomas
JOURNAL OF LIPID RESEARCH
(2020)
Article
Hematology
Bandana Singh, Ramoji Kosuru, Sribalaji Lakshmikanthan, Mary Sorci-Thomas, David Zhang, Rodney Sparapani, Jeannette Vasquez-Vivar, Magdalena Chrzanowska
Summary: The study reveals that Rap1 can protect endothelial cells from atherosclerosis progression in the presence and absence of laminar flow, primarily through promoting NO release and restricting proinflammatory signaling.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Savannah D. Neu, Anna Strzepa, Dustin Martin, Mary G. Sorci-Thomas, Kirkwood A. Pritchard, Bonnie N. Dittel
Summary: This study found that myeloperoxidase inhibition can alleviate the severity of plaque psoriasis in mice. These findings support the role of oxidative damage in psoriasis pathology and suggest potential new therapeutic avenues for further exploration.
Editorial Material
Hematology
Ann Marie Schmidt, Mary G. Sorci-Thomas, Yabing Chen, Robert A. Hegele
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Zhi-Wei Mo, Yue-Ming Peng, Yi-Xin Zhang, Yan Li, Bi-Ang Kang, Ya-Ting Chen, Le Li, Mary G. G. Sorci-Thomas, Yi-Jun Lin, Yang Cao, Si Chen, Ze-Long Liu, Jian-Jun Gao, Zhan-Peng Huang, Jia-Guo Zhou, Mian Wang, Guang-Qi Chang, Meng-Jie Deng, Yu-Jia Liu, Zhen-Sheng Ma, Zuo-Jun Hu, Yu-Gang Dong, Zhi-Jun Ou, Jing-Song Ou
Summary: This study identified a long non-coding RNA, HDRACA, that plays a crucial role in the regulation of angiogenesis by HDL. Normal HDL downregulates the expression of HDRACA, while HDL from patients with coronary artery disease fails to inhibit HDRACA expression effectively, which explains the decreased ability of dysfunctional HDL to stimulate angiogenesis.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Cardiac & Cardiovascular Systems
Jesse W. Williams, Andrew Elvington, Stoyan Ivanov, Skyler Kessler, Hannah Luehmann, Osamu Baba, Brian T. Saunders, Ki-Wook Kim, Michael W. Johnson, Clarissa S. Craft, Jae-Hoon Choi, Mary G. Sorci-Thomas, Bernd H. Zinselmeyer, Jonathan R. Brestoff, Yongjian Liu, Gwendalyn J. Randolph
CIRCULATION RESEARCH
(2017)
Review
Biochemistry & Molecular Biology
Menno Hoekstra, Mary Sorci-Thomas
CURRENT OPINION IN LIPIDOLOGY
(2017)