Article
Multidisciplinary Sciences
Xinbo Zhang, Jeffrey G. McDonald, Binod Aryal, Alberto Canfran-Duque, Emily L. Goldberg, Elisa Araldi, Wen Ding, Yuhua Fan, Bonne M. Thompson, Abhishek K. Singh, Qian Li, George Tellides, Jose Ordovas-Montanes, Rolando Garcia Milian, Vishwa Deep Dixit, Elina Ikonen, Yajaira Suarez, Carlos Fernandez-Hernando
Summary: Desmosterol, the most abundant cholesterol biosynthetic intermediate in human coronary artery lesions, plays an essential role during atherogenesis by integrating with macrophage cholesterol metabolism and inflammatory activation to dampen inflammation and protect from disease progression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Aastha Arora, Gustavo Luis Tripodi, Ilona Kareinen, Martin Berg, Maria Josefa Forteza, Anton Gistera, Silke Griepke, Felipe Beccaria Casagrande, Joilson O. Martins, Dulcineia Saes Parra Abdalla, Jennifer Cole, Claudia Monaco, Daniel F. J. Ketelhuth
Summary: Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that increases cardiovascular disease risk. In a study using mice, it was found that deficiency of the enzyme IDO1 worsened atherosclerosis but had no effect on liver disease. The overexpression of the enzyme TDO2 may play a role in balancing the kynurenine pathway and inflammation in the liver during NASH development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Maria J. Forteza, Martin Berg, Andreas Edsfeldt, Jangming Sun, Roland Baumgartner, Ilona Kareinen, Felipe Beccaria Casagrande, Ulf Hedin, Song Zhang, Ivan Vuckovic, Petras P. Dzeja, Konstantinos A. Polyzos, Anton Gistera, Mette Trauelsen, Thue W. Schwartz, Lea Dib, Joerg Herrmann, Claudia Monaco, Ljubica Matic, Isabel Goncalves, Daniel F. J. Ketelhuth
Summary: Recent studies have shown a link between cellular metabolism and the chronic inflammatory process of atherosclerosis. The PDK/PDH axis has been identified as a major metabolic pathway regulating vascular inflammation and atherogenesis, and targeting it with DCA could be a promising treatment for atherosclerosis.
CARDIOVASCULAR RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Lisa Willemsen, Hung-Jen Chen, Cindy P. A. A. van Roomen, Guillermo R. Griffith, Ricky Siebeler, Annette E. Neele, Jeffrey Kroon, Marten A. Hoeksema, Menno P. J. de Winther
Summary: This study discovered that lipid accumulation in macrophages suppresses the expression of interferon-stimulated genes (ISGs) and secretion of IFN-beta, which can be rescued by exogenous IFN-beta supplementation. Activation of the cholesterol-sensing nuclear liver X receptor (LXR) recapitulated the cholesterol-initiated interferon suppression. Similar interferon suppression was observed in monocytes of familial hypercholesterolemia patients. These findings provide new insights into controlling inflammation in hyperlipidemic conditions and support future therapeutic approaches targeting macrophage reprogramming to reduce atherosclerotic plaque progression and improve stability.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Immunology
Ross O'Hagan, Alex R. Berg, Christin G. Hong, Philip M. Parel, Nehal N. Mehta, Heather L. Teague
Summary: Metabolic conditions such as obesity are becoming more prevalent worldwide and have been linked to early onset cardiovascular disease. Dysregulated cholesterol transport has been found to trigger an overactive systemic inflammatory response, contributing to the development of cardiovascular disease. Accumulation of cholesterol in the bone marrow may also drive systemic inflammation. Current therapeutic strategies target both inflammation and cholesterol transport and biologic therapy is used to restore lipoprotein function and mitigate the immune response.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Adelie Dumont, Man K. S. Lee, Thibault Barouillet, Andrew Murphy, Laurent Yvan-Charvet
Summary: This review discusses the roles of macrophage mitochondrial metabolic diversity in atherosclerosis and their potential as biomarkers. Mitochondria not only play a key role in metabolism but also serve as a signaling platform, integrating various regulations that affect macrophage functions in atherosclerosis. Understanding how these processes are integrated and influence macrophage functions may lead to the development of novel therapeutic approaches.
MOLECULAR ASPECTS OF MEDICINE
(2021)
Article
Endocrinology & Metabolism
Kasparas Petkevicius, Guillaume Bidault, Sam Virtue, Stephen A. Newland, Martin Dale, Aurelien Dugourd, Julio Saez-Rodriguez, Ziad Mallat, Antonio Vidal-Puig
Summary: The study revealed that neuroimmune interactions between the sympathetic nervous system and macrophages do not directly modulate the phenotype of adipose tissue macrophages in mice, but rather exert an indirect effect through the modulation of adipocyte function.
MOLECULAR METABOLISM
(2021)
Review
Immunology
Hossein Halimi, Shirin Farjadian
Summary: High concentrations of cholesterol and its metabolites impede immune responses against cancer cells, but lowering cholesterol levels can have positive effects in the treatment of certain malignancies by inhibiting tumor cell activities and promoting immune responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Lingling Luo, Youming Guo, Lihao Chen, Jing Zhu, Chengrang Li
Summary: Psoriasis is a chronic autoinflammatory skin disease associated with multiple comorbidities, with a prevalence ranging from 2 to 3% in the general population. Alterations in cholesterol and lipid metabolism have been found to be strongly associated with psoriasis, and cytokines such as TNF-alpha and IL-17, which play important roles in the pathogenesis of psoriasis, have been shown to affect cholesterol and lipid metabolism. Cholesterol metabolites and metabolic enzymes, in turn, influence not only the biofunction of keratinocytes in psoriasis, but also the immune response and inflammation. However, the relationship between cholesterol metabolism and psoriasis has not been thoroughly reviewed. This review focuses on cholesterol metabolism disturbances in psoriasis and their crosstalk with psoriatic inflammation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Rebekka Bauer, Sofie Patrizia Meyer, Rebecca Raue, Megan A. Palmer, Vanesa Maria Guerrero Ruiz, Giulia Cardamone, Silvia Roesser, Milou Heffels, Fabian Roesmann, Alexander Wilhelm, Dieter Luetjohann, Kathi Zarnack, Dominik Christian Fuhrmann, Marek Widera, Tobias Schmid, Bernhard Bruene
Summary: Hypoxia reduces cholesterol biosynthesis and activates SREBP2, while increasing interferon-stimulated gene (ISG) expression in monocytes. Intracellular cholesterol distribution plays a critical role in enhancing hypoxic expression of chemokine ISGs. Hypoxia sensitizes TLR4 signaling to enhance chemokine ISG induction following SARS-CoV-2 infection in monocytes, potentially contributing to severe inflammatory responses in COVID-19.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Pharmacology & Pharmacy
Rebekka Bauer, Bernhard Bruene, Tobias Schmid
Summary: The importance of biologically active lipid mediators in regulating inflammation is well recognized. While the relevance of cholesterol in atherosclerosis is widely accepted, its role in inflammatory processes is not well described. This mini-review summarizes the current understanding of cholesterol and its biosynthetic precursors in inflammation regulation, considering their subcellular distributions. Additionally, the inflammation-regulatory effect of cholesterol homeostasis in SARS-CoV-2 infections is discussed.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Genetics & Heredity
Sahar Eshghjoo, Da Mi Kim, Arul Jayaraman, Yuxiang Sun, Robert C. Alaniz
Summary: This article discusses the different roles and metabolic pathways of pro-inflammatory and anti-inflammatory macrophages in atherosclerosis, emphasizing the importance of the polarization state of Macs for the progression and stability of atherosclerotic plaques.
Review
Biochemistry & Molecular Biology
Anastasia V. Poznyak, Dmitry A. Kashirskikh, Vasily N. Sukhorukov, Vladislav Kalmykov, Andrey V. Omelchenko, Alexander N. Orekhov
Summary: Atherosclerosis is a major cause of serious cardiovascular disorders, and its pathogenesis involves multiple processes. Reverse transport of cholesterol is a mechanism that plays a protective role against atherosclerosis. Disordered cholesterol metabolism can result in dyslipidemia and early atherosclerosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Silke Griepke, Mette Trauelsen, Michelle D. Nilsson, Jakob Hansen, Lasse B. Steffensen, Thue W. Schwartz, Daniel F. J. Ketelhuth
Summary: This study found that the complete removal of GPR91 signaling does not influence the chronic inflammatory process of atherosclerosis, as well as the cellular infiltration and macrophage polarization associated with the disease.
Review
Cell Biology
Sheng Xue, Zhe Su, Dacheng Liu
Summary: This review article emphasizes the importance of macrophages in the progression of atherosclerotic cardiovascular disease and their role in maintaining inflammatory response, promoting plaque development, and facilitating thrombosis. It further discusses how metabolic changes and immune response mediate macrophage functional changes in all stages of atherosclerosis.
AGEING RESEARCH REVIEWS
(2023)
Article
Cardiac & Cardiovascular Systems
Andrea Baragetti, Fabrizia Bonacina, Lorenzo Da Dalt, Annalisa Moregola, Veronica Zampoleri, Fabio Pellegatta, Liliana Grigore, Angela Pirillo, Rossella Spina, Angelo Baldassarre Cefalu, Maurizio Averna, Giuseppe D. Norata, Alberico L. Catapano
Summary: In subjects with familial hypercholesterolaemia (FH), there is a correlation between elevated LDL cholesterol and shorter leukocyte telomere length (LTL), accompanied by reduced circulating hematopoietic precursors and decreased bone marrow resident long-term hematopoietic stem and progenitor cells (LT-HSPCs).
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Madeeha H. Sheikh, Mariella Errede, Antonio D'Amati, Noorafza Q. Khan, Silvia Fanti, Rodrigo A. Loiola, Simon McArthur, Gareth S. D. Purvis, Caroline E. O'Riordan, Davide Ferorelli, Alessandro Dell'Erba, Julius Kieswich, Chis Reutelingsperger, Eugenio Maiorano, Magdi Yaqoob, Christoph Thiemermann, Andrea Baragetti, Alberico Luigi Catapano, Giuseppe Danilo Norata, Federica Marelli-Berg, Daniela Virgintino, Egle Solito
Summary: Mounting evidence suggests a link between metabolic disease and neurovascular disorders and cognitive decline. This study used mouse models and post-mortem brains of T2DM patients to show that metabolic disease damages the blood-brain barrier (BBB), leading to increased leukocyte extravasation and neuroinflammation. Therapeutic interventions such as pharmacological treatment and dietary changes were found to reduce BBB damage.
Letter
Hematology
Marco Busnelli, Stefano Manzini, Alice Colombo, Fabrizia Bonacina, Giuseppe D. Norata, Elsa Franchi, Silvia Castiglioni, Christos Andronis, Eftychia Lekka, Eugenio Scanziani, Giulia Chiesa
THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Cell Biology
Fabrizia Bonacina, Annalisa Moregola, Monika Svecla, David Coe, Patrizia Uboldi, Sara Fraire, Simona Beretta, Giangiacomo Beretta, Fabio Pellegatta, Alberico Luigi Catapano, Federica M. Marelli-Berg, Giuseppe Danilo Norata
Summary: Increased cholesterol uptake by the LDLR plays a role in the immunometabolic response of activated CD8(+) T cells through the modulation of lysosome-mTORC1 axis. The findings suggest the potential of selectively targeting LDLR for enhancing CD8-dependent immune response.
JOURNAL OF CELL BIOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Menno P. J. de Winther, Magnus Back, Paul Evans, Delphine Gomez, Isabel Goncalves, Helle F. Jorgensen, Rory R. Koenen, Esther Lutgens, Giuseppe Danilo Norata, Elena Osto, Lea Dib, Michael Simons, Konstantinos Stellos, Seppo Yla-Herttuala, Holger Winkels, Marie-Luce Bochaton-Piallat, Claudia Monaco
Summary: The advent of single-cell biology has opened up new possibilities for understanding human biological processes and diagnosing, monitoring, and treating diseases, including cardiovascular disease (CVD). By analyzing CVD samples at the single-cell level, new cell communities that play a role in disease development can be identified, leading to new therapeutic strategies. This review focuses on the single-cell analysis of atherosclerotic plaques, highlighting the current understanding of cellular subpopulations and their heterogeneity and plasticity in relation to clinically relevant features. The clinical impact of single-cell technologies in CVD patient care is emphasized, calling for multidisciplinary and international collaborative efforts.
EUROPEAN HEART JOURNAL
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Fabrizia Bonacina, Giuseppe Danilo Norata
EUROPEAN HEART JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Jasmine Nour, Annalisa Moregola, Monika Svecla, Lorenzo Da Dalt, Rossella Bellini, Olivier Neyrolles, Gian Paolo Fadini, Yoann Rombouts, Mattia Albiero, Fabrizia Bonacina, Giuseppe Danilo Norata
Summary: Research has shown that during a high-fat diet, deficiency of the mannose receptor affects bone marrow and circulating immune cell subsets, leading to reduced systemic inflammation and resistance to obesity development.
Editorial Material
Cardiac & Cardiovascular Systems
Laura Calabresi, Giuseppe Danilo Norata
CARDIOVASCULAR RESEARCH
(2023)
Article
Endocrinology & Metabolism
Laurent Yvan-Charvet, Edward Benjamin Thorp
Summary: Glycolysis fuels inflammatory response in macrophages and produces pyruvate. However, a study in Nature Metabolism by Ran et al. shows that transporting pyruvate to the mitochondria for Krebs cycle is not necessary for inflammation.
Review
Cardiac & Cardiovascular Systems
Jasmine Nour, Fabrizia Bonacina, Giuseppe D. Norata
Summary: Epidemiological data and interventional studies suggest that women have a lower risk of cardiovascular disease compared to men until menopause. The molecular mechanisms underlying this difference are still debated, but experimental models have shown that estrogen receptor activation is atheroprotective. Additionally, the importance of sex chromosome complement on atherosclerosis beyond sex hormones is also worth investigating.
Review
Cardiac & Cardiovascular Systems
Lorenzo Da Dalt, Ainara G. Cabodevilla, Ira J. Goldberg, Giuseppe Danilo Norata
Summary: Maintaining a balance in energy utilization is crucial for metabolic tissues, especially the heart. Changes in energetic substrate preference and disruptions in lipid metabolism can lead to heart failure. This review focuses on the sources and uptake pathways of fatty acids in cardiomyocytes, as well as the mechanisms of lipid storage, oxidation, and the role of cholesterol accumulation in heart dysfunction.
CARDIOVASCULAR RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Lorenzo Da Dalt, Annalisa Moregola, Monika Svecla, Silvia Pedretti, Francesca Fantini, Mirko Ronzio, Patrizia Uboldi, Diletta Dolfini, Elena Donetti, Andrea Baragetti, Nico Mitro, Luca Scorrano, Giuseppe Danilo Norata
Summary: Impairment of mitochondrial fusion affects the development of liver steatosis and obesity. Mice lacking OPA1 are protected from high-fat diet-induced metabolic dysfunction due to reduced lipid absorption.
CARDIOVASCULAR RESEARCH
(2023)
Review
Peripheral Vascular Disease
Maciej Banach, Giuseppe Danilo Norata
Summary: Elevated levels of LDL-C increase the risk of atherosclerotic cardiovascular disease (ASCVD), and reducing LDL-C levels can lower the risk of cardiovascular adverse events. Red yeast rice (RYR) has cholesterol-lowering effects due to its bioactive components (monacolins) that inhibit the activity of HMG-CoA reductase. However, the use of RYR as a food supplement at a dose of 10 mg/day raises significant safety concerns, and serious adverse effects have been reported at even lower doses.
CURRENT ATHEROSCLEROSIS REPORTS
(2023)
Article
Immunology
Rossella Bellini, Annalisa Moregola, Jasmine Nour, Patrizia Uboldi, Fabrizia Bonacina, Giuseppe D. Norata
Summary: DCIR2 deficiency affects the distribution of dendritic cells in the liver and adipose tissue, but not lipid accumulation. It has a redundant role in the progression of obesity and inflammation.
IMMUNITY INFLAMMATION AND DISEASE
(2023)
Article
Peripheral Vascular Disease
Vivek Krishna Pulakazhi Venu, Annalisa Moregola, Lorenzo Da Dalt, Patrizia Uboldi, Fabrizia Bonacina, Andres Fernando Muro, Giuseppe Danilo Norata
Summary: This study investigates the role of the Extra Domain A (EDA) of fibronectin in sepsis. Results show that mice with EDA expression are protected against sepsis, and neutrophils bind more to FN_EDA+ surface, potentially limiting over-reactivity.
ATHEROSCLEROSIS PLUS
(2023)