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JOURNAL ARTICLE
Xiaoxi Fan, Jibo Han, Lingfeng Zhong, Wenyuan Zheng, Ruiyin Shao, Yucong Zhang, Si Shi, Shuang Lin, Zhouqing Huang, Weijian Huang, Xueli Cai, Bozhi Ye
BACKGROUND: Macrophages play a crucial role in atherosclerotic plaque formation, and the death of macrophages is a vital factor in determining the fate of atherosclerosis. GSDMD (gasdermin D)-mediated pyroptosis is a programmed cell death, characterized by membrane pore formation and inflammatory factor release. METHODS: ApoE -/- and Gsdmd -/- ApoE -/- mice, bone marrow transplantation, and AAV-F4/80-shGSDMD were used to examine the effect of macrophage-derived GSDMD on atherosclerosis...
May 2, 2024: Arteriosclerosis, Thrombosis, and Vascular Biology
#2
JOURNAL ARTICLE
Lina Vandermeulen, Ivana Geric, Laura Fumagalli, Mohamed Kreir, Ashley Lu, Annelies Nonneman, Jessie Premereur, Leen Wolfs, Rafaela Policarpo, Nicola Fattorelli, An De Bondt, Ilse Van Den Wyngaert, Bob Asselbergh, Mark Fiers, Bart De Strooper, Constantin d'Ydewalle, Renzo Mancuso
BACKGROUND: Microglia play important roles in maintaining brain homeostasis and neurodegeneration. The discovery of genetic variants in genes predominately or exclusively expressed in myeloid cells, such as Apolipoprotein E (APOE) and triggering receptor expressed on myeloid cells 2 (TREM2), as the strongest risk factors for Alzheimer's disease (AD) highlights the importance of microglial biology in the brain. The sequence, structure and function of several microglial proteins are poorly conserved across species, which has hampered the development of strategies aiming to modulate the expression of specific microglial genes...
April 24, 2024: Molecular Neurodegeneration
#3
JOURNAL ARTICLE
Remo Poto, Gianni Marone, Stephen J Galli, Gilda Varricchi
Mast cells are tissue-resident immune cells strategically located in different compartments of the normal human heart (the myocardium, pericardium, aortic valve and close to nerves) as well as in atherosclerotic plaques. Cardiac mast cells produce a broad spectrum of vasoactive and proinflammatory mediators, which have potential roles in inflammation, angiogenesis, lymphangiogenesis, tissue remodeling and fibrosis. Mast cells release preformed mediators (e.g., histamine, tryptase, chymase) and de novo synthesized mediators [e...
April 17, 2024: Cardiovascular Research
#4
JOURNAL ARTICLE
Tim Bathe, Gabriela P Hery, Jonathan A B Villareal, Jennifer L Phillips, Eric M Cohen, Rohan V Sharma, Wangchen Tsering, Stefan Prokop
The disease-specific accumulation of pathological proteins has long been the major focus of research in neurodegenerative diseases (ND), including Alzheimer's disease (AD) and related dementias (RD), but the recent identification of a multitude of genetic risk factors for ND in immune-associated genes highlights the importance of immune processes in disease pathogenesis and progression. Studies in animal models have characterized the local immune response to disease-specific proteins in AD and ADRD, but due to the complexity of disease processes and the co-existence of multiple protein pathologies in human donor brains, the precise role of immune processes in ND is far from understood...
April 5, 2024: Acta Neuropathologica Communications
#5
JOURNAL ARTICLE
Nathalie Mantel, Fabienne Piras-Douce, Emilie Chautard, Ernesto Marcos-Lopez, Caroline L Bodinham, Antonio Cosma, Virginie Courtois, Nina Dhooge, Sylviane Gautheron, Stefan H E Kaufmann, Kathleen Pizzoferro, David J M Lewis, Frédéric Martinon, Anke Pagnon, Franck Raynal, Nathalie Dereuddre-Bosquet, Roger Le Grand
The non-human primate (NHP) model (specifically rhesus and cynomolgus macaques) has facilitated our understanding of the pathogenic mechanisms of yellow fever (YF) disease and allowed the evaluation of the safety and efficacy of YF-17D vaccines. However, the accuracy of this model in mimicking vaccine-induced immunity in humans remains to be fully determined. We used a systems biology approach to compare hematological, biochemical, transcriptomic, and innate and antibody-mediated immune responses in cynomolgus macaques and human participants following YF-17D vaccination...
April 3, 2024: Journal of Virology
#6
JOURNAL ARTICLE
Renzo Mancuso, Nicola Fattorelli, Anna Martinez-Muriana, Emma Davis, Leen Wolfs, Johanna Van Den Daele, Ivana Geric, Jessie Premereur, Paula Polanco, Baukje Bijnens, Pranav Preman, Lutgarde Serneels, Suresh Poovathingal, Sriram Balusu, Catherine Verfaillie, Mark Fiers, Bart De Strooper
Microglia are central players in Alzheimer's disease pathology but analyzing microglial states in human brain samples is challenging due to genetic diversity, postmortem delay and admixture of pathologies. To circumvent these issues, here we generated 138,577 single-cell expression profiles of human stem cell-derived microglia xenotransplanted in the brain of the AppNL-G-F model of amyloid pathology and wild-type controls. Xenografted human microglia adopt a disease-associated profile similar to that seen in mouse microglia, but display a more pronounced human leukocyte antigen or HLA state, likely related to antigen presentation in response to amyloid plaques...
March 27, 2024: Nature Neuroscience
#7
JOURNAL ARTICLE
Rafael Escate, Teresa Padró, Leopoldo Pérez de Isla, Francisco Fuentes, Rodrigo Alonso, Pedro Mata, Lina Badimon
BACKGROUND AND AIMS: Premature atherosclerotic cardiovascular disease (CVD) is a clinic characteristic of familial hypercholesterolemia (FH). Coronary calcium score (CCS) is a highly used imaging modality to evidence atherosclerotic plaque burden. microRNAs (miRNAs) are non-coding RNAs that epigenetically regulate gene expression. Here, we investigated whether CCS associates with a specific miRNA-signature in FH-patients. METHODS: Patients with genetic diagnosis of FH (N = 86) from the nationwide SAFEHEART-cohort were investigated by computed tomography angiography imaging and classified depending on the presence of coronary calcification in FH-CCS (+) and FH-CCS (-) groups by the Agatston score...
March 8, 2024: Atherosclerosis
#8
JOURNAL ARTICLE
Claire A Butler, Adrian Mendoza Arvilla, Giedre Milinkeviciute, Celia Da Cunha, Shimako Kawauchi, Narges Rezaie, Heidi Y Liang, Dominic Javonillo, Annie Thach, Shuling Wang, Sherilyn Collins, Amber Walker, Kai-Xuan Shi, Jonathan Neumann, Angela Gomez-Arboledas, Caden M Henningfield, Lindsay A Hohsfield, Mark Mapstone, Andrea J Tenner, Frank M LaFerla, Ali Mortazavi, Grant R MacGregor, Kim N Green
BACKGROUND: Variants in ABCA7, a member of the ABC transporter superfamily, have been associated with increased risk for developing late onset Alzheimer's disease (LOAD). METHODS: CRISPR-Cas9 was used to generate an Abca7V1613M variant in mice, modeling the homologous human ABCA7V1599M variant, and extensive characterization was performed. RESULTS: Abca7V1613M microglia show differential gene expression profiles upon lipopolysaccharide challenge and increased phagocytic capacity...
March 20, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
#9
JOURNAL ARTICLE
Yu-Xiang Yan, Ya-Ke Lu, Yu-Hong Liu, Jie Zhang, Shuo Wang, Jing Dong, Huan-Bo Xiao
BACKGROUND AND AIMS: NLRP3 inflammasome plays a key role in vascular inflammation and atherosclerosis. Circular RNAs (circRNAs) are involved in disease development by regulating gene expression, and have emerged as promising novel disease biomarkers. This study aimed to identify the NLRP3 inflammasome-associated circRNA biomarkers of carotid atherosclerosis. METHODS: Based on the differential expression profiles of circRNAs in patients with carotid artery plaque (CAP) and healthy controls, hsa_circ_0043621, hsa_circ_0051995, and hsa_circ_0123388 were screened and validated using real-time quantitative polymerase chain reaction (RT-qPCR)...
February 29, 2024: Atherosclerosis
#10
JOURNAL ARTICLE
Ivan Pinos, Johana Coronel, Asma'a Albakri, Amparo Blanco, Patrick McQueen, Donald Molina, JaeYoung Sim, Edward A Fisher, Jaume Amengual
β-Carotene oxygenase 1 (BCO1) catalyzes the cleavage of β-carotene to form vitamin A. Besides its role in vision, vitamin A regulates the expression of genes involved in lipid metabolism and immune cell differentiation. BCO1 activity is associated with the reduction of plasma cholesterol in humans and mice, while dietary β-carotene reduces hepatic lipid secretion and delays atherosclerosis progression in various experimental models. Here we show that β-carotene also accelerates atherosclerosis resolution in two independent murine models, independently of changes in body weight gain or plasma lipid profile...
February 6, 2024: ELife
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Leelavathi N Madhu, Maheedhar Kodali, Raghavendra Upadhya, Shama Rao, Bing Shuai, Yogish Somayaji, Sahithi Attaluri, Maha Kirmani, Shreyan Gupta, Nathaniel Maness, Xiaolan Rao, James Cai, Ashok K Shetty
Antiinflammatory extracellular vesicles (EVs) derived from human induced pluripotent stem cell (hiPSC)-derived neural stem cells (NSCs) hold promise as a disease-modifying biologic for Alzheimer's disease (AD). This study directly addressed this issue by examining the effects of intranasal administrations of hiPSC-NSC-EVs to 3-month-old 5xFAD mice. The EVs were internalized by all microglia, which led to reduced expression of multiple genes associated with disease-associated microglia, inflammasome, and interferon-1 signaling...
January 19, 2024: bioRxiv
#12
JOURNAL ARTICLE
Aarthi Ravindran, Lari Holappa, Henri Niskanen, Ilya Skovorodkin, Susanna Kaisto, Mustafa Beter, Miika Kiema, Ilakya Selvarajan, Valtteri Nurminen, Einari Aavik, Rédouane Aherrahrou, Sanna Pasonen-Seppänen, Vittorio Fortino, Johanna P Laakkonen, Seppo Ylä-Herttuala, Seppo Vainio, Tiit Örd, Minna U Kaikkonen
AIMS: Vascular smooth muscle cells (SMCs) and their derivatives are key contributors to the development of atherosclerosis. However, studying changes in SMC gene expression in heterogeneous vascular tissues is challenging due to the technical limitations and high cost associated with current approaches. In this paper, we apply Translating Ribosome Affinity Purification sequencing (TRAP-Seq) to profile SMC-specific gene expression directly from tissue. METHODS AND RESULTS: To facilitate SMC-specific translatome analysis, we generated SMCTRAP mice, a transgenic mouse line expressing EGFP-tagged ribosomal protein L10a (EGFP-L10a) under the control of the SMC-specific αSMA promoter...
January 30, 2024: Cardiovascular Research
#13
JOURNAL ARTICLE
Bing Dai, Cunfa Liu, Song Zhang, Mei Huang, Shugang Yin
Elevated levels of plasma triglycerides (TG) and cholesterol have been shown to contribute to the pathogenesis of several cardiovascular risk factors, such as atherosclerosis, a primary cause of mortality. Gastrodin (Gas) is an effective polyphenol extracted from Chinese natural herbal Gastrodiae elata Blume, which has been documented to be effective against atherosclerosis. However, the related mechanisms remain largely unclear. The current investigation elucidated the involvement of Gas in the development of AS generated by a high-fat diet in mice lacking the apolipoprotein E gene (ApoE-/- )...
January 25, 2024: Cell Biochemistry and Biophysics
#14
JOURNAL ARTICLE
Michele Biagioli, Silvia Marchianò, Cristina Di Giorgio, Martina Bordoni, Ginevra Urbani, Rachele Bellini, Carmen Massa, Rana Sami Ullah Khan, Rosalinda Roselli, Maria Chiara Monti, Elva Morretta, Antonino Giordano, Valentina Vellecco, Mariarosaria Bucci, Asif Jilani Iqbal, Anella Saviano, Adel Ab Mansour, Patrizia Ricci, Eleonora Distrutti, Angela Zampella, Enrico Cieri, Giuseppe Cirino, Stefano Fiorucci
While patients with nonalcoholic fatty liver disease (NAFLD) are at increased risk to develop clinically meaningful cardiovascular diseases (CVD), there are no approved drug designed to target the liver and CVD component of NAFLD. GPBAR1, also known as TGR5, is a G protein coupled receptor for secondary bile acids. In this study we have investigated the effect of GPBAR1 activation by BAR501, a selective GPBAR1 agonist, in Apolipoprotein E deficient (ApoE-/- ) mice fed a high fat diet and fructose (Western diet), a validated model of NAFLD-associated atherosclerosis...
December 2023: Biochemical Pharmacology
#15
JOURNAL ARTICLE
Phoebe Valdes, Kenneth W Henry, Michael Q Fitzgerald, Koushik Muralidharan, Andrew B Caldwell, Srinivasan Ramachandran, Lawrence S B Goldstein, William C Mobley, Douglas R Galasko, Shankar Subramaniam
Non-familial Alzheimer's disease (AD) occurring before 65 years of age is commonly referred to as early-onset Alzheimer's disease (EOAD) and constitutes ~ 5-6% of all AD cases (Mendez et al. in Continuum 25:34-51, 2019). While EOAD exhibits the same clinicopathological changes such as amyloid plaques, neurofibrillary tangles (NFTs), brain atrophy, and cognitive decline (Sirkis et al. in Mol Psychiatry 27:2674-88, 2022; Caldwell et al. in Mol Brain 15:83, 2022) as observed in the more prevalent late-onset AD (LOAD), EOAD patients tend to have more severe cognitive deficits, including visuospatial, language, and executive dysfunction (Sirkis et al...
November 3, 2023: Molecular Brain
#16
JOURNAL ARTICLE
Michal Mokry, Arjan Boltjes, Lotte Slenders, Gemma Bel-Bordes, Kai Cui, Eli Brouwer, Joost M Mekke, Marie A C Depuydt, Nathalie Timmerman, Farahnaz Waissi, Maarten C Verwer, Adam W Turner, Mohammad Daud Khan, Chani J Hodonsky, Ernest Diez Benavente, Robin J G Hartman, Noortje A M van den Dungen, Nico Lansu, Emilia Nagyova, Koen H M Prange, Jason C Kovacic, Johan L M Björkegren, Eleftherios Pavlos, Evangelos Andreakos, Heribert Schunkert, Gary K Owens, Claudia Monaco, Aloke V Finn, Renu Virmani, Nicholas J Leeper, Menno P J de Winther, Johan Kuiper, Gert J de Borst, Erik S G Stroes, Mete Civelek, Dominique P V de Kleijn, Hester M den Ruijter, Folkert W Asselbergs, Sander W van der Laan, Clint L Miller, Gerard Pasterkamp
Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved sub-phenotyping. Here we analyze the gene expression profiles of 654 advanced human carotid plaques. The unsupervised, transcriptome-driven clustering revealed five dominant plaque types. These plaque phenotypes were associated with clinical presentation and showed differences in cellular compositions. Validation in coronary segments showed that the molecular signature of these plaques was linked to coronary ischemia...
December 2022: Nat Cardiovasc Res
#17
JOURNAL ARTICLE
Christian Griñán-Ferré, Júlia Jarné-Ferrer, Aina Bellver-Sanchís, Sandra Codony, Dolors Puigoriol-Illamola, Coral Sanfeliu, Yumin Oh, Seulki Lee, Santiago Vázquez, Mercè Pallàs
BACKGROUND: Neuroinflammation is widely recognized as a significant hallmark of Alzheimer's disease (AD). To combat neuroinflammation, the inhibition of the soluble epoxide hydrolase (sEH) enzyme has been demonstrated crucial. Importantly, sEH inhibition could be related to other neuroprotective pathways described in AD. AIMS: The aim of the study was to unveil new molecular pathways driving neuroprotection through sEH, we used an optimized, potent, and selective sEH inhibitor (sEHi, UB-SCG-51)...
October 31, 2023: CNS Neuroscience & Therapeutics
#18
JOURNAL ARTICLE
Claudia Bruedigam, Johannes P T M van Leeuwen, Jeroen van de Peppel
Clinical studies revealed detrimental skeletal and vascular effects of the insulin sensitizer rosiglitazone. We have shown earlier that rosiglitazone accelerates osteoblast differentiation from human mesenchymal stem cells (hMSC) at the expense of increased oxidative stress and cell death. In calcifying human vascular cells, rosiglitazone stimulates pathological mineralization, an effect diminished by the antioxidant resveratrol. Here, we aimed to elucidate transcriptional networks underlying the rosiglitazone-enhanced mineralization phenotype...
October 16, 2023: Cells
#19
JOURNAL ARTICLE
Ana Raquel Melo de Farias, Alexandre Pelletier, Lukas Cruz Carvalho Iohan, Orthis Saha, Amélie Bonnefond, Philippe Amouyel, Fabien Delahaye, Jean-Charles Lambert, Marcos R Costa
Alzheimer's disease (AD) is the most prevalent cause of dementia in the elderly, characterized by the presence of amyloid-beta (Aβ) plaques, neurofibrillary tangles, neuroinflammation, synapse loss and neurodegeneration in the brain. The amyloid cascade hypothesis postulates that deposition of Aβ peptides is the causative agent of AD pathology, but we still lack comprehensive understanding of the molecular mechanisms connecting Aβ peptides to neuronal dysfunctions in AD. In this work, we investigate the early effects of Aβ peptide accumulation on the functional properties and gene expression profiles of human-induced neurons (hiNs)...
September 18, 2023: Biomedicines
#20
JOURNAL ARTICLE
Jolanta Wiejak, Fiona A Murphy, Pasquale Maffia, Stephen J Yarwood
Atherosclerosis is a serious cardiovascular disease that is characterised by the development of atheroma, which are lipid-laden plaques that build up within arterial walls due to chronic inflammatory processes. These lesions are fundamentally attributed to a complex cellular crosstalk between vascular smooth muscle cells (VSMCs), vascular endothelial cells (VECs) and central immune cells, such as macrophages (Mɸs), which promote vascular inflammation. The presence of VSMCs exerts both positive and negative effects during atheroma development, which can be attributed to their phenotypic plasticity...
September 23, 2023: Scientific Reports
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