Article
Engineering, Environmental
Xinming Shen, Qiang Li, Wenxin Hu, Min Yang, Wei An, Jianying Hu
Summary: This study reveals that drinking water from six major cities in China can significantly promote foam cell formation in atherosclerosis, and chemicals in the water may play a role in this process by antagonizing liver X receptor alpha.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nan Hu, Xixi Zeng, Feifei Tang, Sizheng Xiong
Summary: The study demonstrated that the upregulation of LIPCAR in patients with atherosclerosis compared to healthy individuals, and silencing LIPCAR could reverse ox-LDL-induced THP1 cell apoptosis. Furthermore, the upregulation of LIPCAR in exosomes derived from ox-LDL treated THP-1 cells promoted the proliferation of VSMCs.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Plant Sciences
Tao-tao Wang, Cheng-yong Yang, Li Peng, Li Li, Nan-ting Chen, Xue Feng, Jing Xie, Ting-chun Wu, Tao Xu, Yun-zhi Chen
Summary: QSYQ has been found to have an anti-atherosclerotic effect by targeting TTC39B-LXR mediated reverse cholesterol transport in the liver. QSYQ not only promotes reverse cholesterol transport, but also improves fatty liver and protects liver function.
Article
Cell & Tissue Engineering
Adil Rasheed, Sarah A. Shawky, Ricky Tsai, Richard G. Jung, Trevor Simard, Michael F. Saikali, Benjamin Hibbert, Katey J. Rayner, Carolyn L. Cummins
Summary: Activation of LXR in EOCs leads to the production of secreted factors that reduce early atherosclerosis development by decreasing monocyte adhesion to activated endothelial cells. This finding has potential implications for the treatment of cardiovascular disease in both mice and human patients.
STEM CELLS TRANSLATIONAL MEDICINE
(2021)
Article
Cell Biology
Shulan Pi, Ling Mao, Jiefang Chen, Hanqing Shi, Yuxiao Liu, Xiaoqing Guo, Yuanyuan Li, Lian Zhou, Hui He, Cheng Yu, Jianyong Liu, Yiping Dang, Yuanpeng Xia, Quanwei He, Huijuan Jin, Yanan Li, Yu Hu, Yiliang Miao, Zhenyu Yue, Bo Hu
Summary: The P2RY12 receptor plays a crucial role in regulating macrophagy and VSMC-derived foam cell formation in advanced atherosclerosis, by inhibiting cholesterol efflux and blocking autophagy pathways. Inhibition of the P2RY12 receptor may be a potential therapeutic target for treating atherosclerosis.
Review
Biochemistry & Molecular Biology
Anastasia Poznyak, Nikita G. Nikiforov, Antonina Starodubova, Tatyana Popkova, Alexander N. Orekhov
Summary: Atherosclerosis remains a major cause of death globally, primarily due to the lack of effective preventive and therapeutic measures. Lifestyle and genetic factors play significant roles in the development of the disease.
Article
Biochemistry & Molecular Biology
Koki Tachibana, Kohshi Kusumoto, Mai Ogawa, Hidenori Ando, Taro Shimizu, Yu Ishima, Tatsuhiro Ishida, Keiichiro Okuhira
Summary: Formation of foam cells in atherosclerosis is caused by excessive lipid accumulation by macrophages. FTY720 has been shown to inhibit atherosclerotic plaque development, and this study reveals that FTY720 induces ABCA1 expression through SphK2-mediated acetylation of H3K9, leading to suppression of lipid accumulation in macrophages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Kaori Endo-Umeda, Eunyoung Kim, David G. Thomas, Wenli Liu, Huijuan Dou, Mustafa Yalcinkaya, Sandra Abramowicz, Tong Xiao, Per Antonson, Jan-Ake Gustafsson, Makoto Makishima, Muredach P. Reilly, Nan Wang, Alan R. Tall
Summary: Our study reveals the crucial role of macrophage LXRs in promoting the Trem2 gene expression program and suppressing inflammation in foam cells of atherosclerotic plaques.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Genetics & Heredity
Emin Grbic, Natasa Gorkic, Ales Pleskovic, Farid Ljuca, Mladen Gasparini, Bozidar Mrda, Ines Cilensek, Zlatko Fras, Daniel Petrovic
Summary: In the Slovenian cohort, the LXRA gene rs2279238 polymorphism is significantly associated with the onset and progression of carotid atherosclerosis.
Article
Biochemistry & Molecular Biology
Kezhou Wang, Wei Zhou, Gaolei Hu, Lifeng Wang, Rong Cai, Tian Tian
Summary: The deSUMOylation of Transcription factor EB (TFEB) can inhibit the formation of macrophage foam cells by enhancing lysosomal biogenesis and autophagy, thus reducing the development of atherosclerosis (AS).
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Shreya R. Savla, Kedar S. Prabhavalkar, Lokesh K. Bhatt
Summary: LXRs are important regulators of atherosclerosis and understanding their role is important for developing potential therapeutics. This review discusses the role of LXRs in atherosclerotic development, LXR agonists, and future research directions. It highlights the need for further research on specific agonist-targeted LXR isoforms and cell type-specific knockout models.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2022)
Article
Biochemistry & Molecular Biology
Takayuki Iwaki, Tomohiro Arakawa, Mayra J. Sandoval-Cooper, Denise L. Smith, Deborah Donahue, Victoria A. Ploplis, Kazuo Umemura, Francis J. Castellino
Summary: The study showed that plasminogen exacerbates the progression of atherosclerosis in an LDL-C model and is also involved in the modification and clearance of lipoproteins. Controlling the plasminogen system on macrophages may be a novel therapeutic approach to prevent foam cell formation.
Article
Biochemistry & Molecular Biology
Xiao Li, Tengfei Zheng, Yu Zhang, Yachao Zhao, Fengming Liu, Shen Dai, Xiaolin Liu, Mei Zhang
Summary: This study found that DKK1 promotes smooth muscle cell foam cell formation during atherosclerosis by reducing CYP4A11-20-HETE/SREBP2-mediated ABCA1 expression.
Article
Medicine, Research & Experimental
Elizabeth L. Kilby, Daniel M. Kelly, T. Hugh Jones
Summary: The study demonstrates that testosterone can promote cholesterol clearance in human macrophages by activating LXRα and downstream targets, potentially explaining the anti-atherogenic effects of testosterone in clinical settings.
Review
Immunology
Jiaqi Zhang, Mengru Xie, Xiaofei Huang, Guangjin Chen, Ying Yin, Xiaofeng Lu, Guangxia Feng, Ran Yu, Lili Chen
Summary: Atherosclerosis (AS) is increasingly recognized as a chronic inflammatory disease, related to infectious diseases such as periodontitis. Porphyromonas gingivalis (P. gingivalis) is commonly found in atherosclerotic plaque in AS patients and can influence the function of various cells, ultimately promoting the occurrence and development of atherosclerosis. Elucidating the underlying mechanisms of P. gingivalis in AS provides new insights for preventing or slowing down the progression of AS by inhibiting periodontal pathogens.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemical Research Methods
Niek S. A. Crone, Niek van Hilten, Alex van der Ham, Herre Jelger Risselada, Alexander Kros, Aimee L. Boyle
Summary: Coiled-coil peptides are attractive for biomaterial preparation due to their high-affinity, selective, self-assembling binding motifs. Photocontrol of coiled-coil self-assembly offers precise localization of their activity. This study prepared three azobenzene-containing amino acids and incorporated them into a model coiled coil. The results showed that the presence of these amino acids affected coiled-coil binding strength and folding, with the size of the amino acid having an impact on photoisomerization. Molecular dynamics simulations supported the hypothesis that the positioning of the diazene group and reduction of amino acid rotations influenced coiled-coil assembly. This strategy of using photoswitchable amino acids shows potential for controlling biomaterial assembly.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Jolinde van Strien, Oscar Escalona-Rayo, Wim Jiskoot, Bram Slutter, Alexander Kros
Summary: ELP-based nanomaterials, particularly micelles assembled from amphiphilic ELP diblock copolymers, show great potential as drug delivery systems due to their biodegradability and the ability to control particle design. The cargo can be shielded inside the micelle core or reside in the corona through site-specific attachment to the hydrophobic or hydrophilic block of the ELP. Various types of cargo, including protein, peptide, and small molecule drugs, can be loaded onto or entrapped inside the micelles.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Engineering, Biomedical
Gabriela Arias-Alpizar, Panagiota Papadopoulou, Xabier Rios, Krishna Reddy Pulagam, Mohammad-Amin Moradi, Roy Pattipeiluhu, Jeroen Bussmann, Nico Sommerdijk, Jordi Llop, Alexander Kros, Frederick Campbell
Summary: Plasma lipid transport and metabolism are crucial for cellular function. A lipid nanoparticle formulation composed of two lipids can effectively be recognized and taken up by specific endothelial cell subsets through a lipase-mediated pathway. The liposome-lipase interaction is mediated by a unique liposome morphology. These compositionally simplistic liposomes provide new insights into the design of lipid-based nanoparticles for targeted delivery in vivo.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Materials Science, Biomaterials
Ye Zeng, Oscar Escalona-Rayo, Renzo Knol, Alexander Kros, Bram Slutter
Summary: mRNA vaccines are potent immune activators that induce robust T cell immune responses, playing crucial roles in tumor immunotherapy and protection against infectious diseases. Optimizing the lipid composition and formulation of lipid nanoparticles (LNPs) can enhance their efficacy. It has been found that using beta-sitosterol and DOPE lipids can improve the efficiency of mRNA delivery to immune cells and enhance immune responses.
BIOMATERIALS SCIENCE
(2023)
Review
Hematology
Menno Hoekstra, Miranda Van Eck, Theo J. C. Van Berkel
Summary: Hyperlipidemia is a major risk factor for atherosclerotic cardiovascular disease, and gene therapy has shown potential in treating dyslipidemia. This review focuses on hepatocyte-directed base editing as a genetic modification approach to improve the treatment of human dyslipidemia and suggests further technological advancements.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Robin A. F. Verwilligen, Lindsay Mulder, Pedro M. Araujo, Miguel Carneiro, Jeroen Bussmann, Menno Hoekstra, Miranda Van Eck
Summary: Scavenger receptor class B1 (SCARB1) is a multi-ligand scavenger receptor that is primarily expressed in liver and steroidogenic organs. This study created two stable scarb1 knockout zebrafish lines and found that SCARB1 deficiency in zebrafish leads to disruption of carotenoid-based pigmentation, reduced fertility, and decreased larvae survival rate. It also affects the uptake of HDL in the liver, but this is attributed to reduced perfusion.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2023)
Article
Chemistry, Multidisciplinary
Xue-Quan Zhou, Peiyuan Wang, Vadde Ramu, Liyan Zhang, Suhua Jiang, Xuezhao Li, Selda Abyar, Panagiota Papadopoulou, Yang Shao, Ludovic Bretin, Maxime A. A. Siegler, Francesco Buda, Alexander Kros, Jiangli Fan, Xiaojun Peng, Wen Sun, Sylvestre Bonnet
Summary: This article reports that the metallophilic interaction between cyclometalated palladium complexes generates supramolecular nanostructures in living mice with long circulation time and efficient tumour accumulation rate. Green light activation leads to efficient tumour destruction due to the self-assembled palladium complexes.
Article
Chemistry, Multidisciplinary
Ye Zeng, Mengjie Shen, Ankush Singhal, Geert Jan Agur Sevink, Niek Crone, Aimee L. L. Boyle, Alexander Kros
Summary: An ideal nanomedicine system improves drug therapy by enhancing cellular uptake. However, current nanomedicines mainly enter cells through endosomal/lysosomal pathways, leading to inefficient delivery of therapeutic cargo. To overcome this issue, the authors developed a synthetic lipidated peptide pair, E4/K4, inspired by natural fusion machinery. By optimizing the structure of the peptide, the researchers achieved enhanced membrane fusion and efficient delivery of drugs into cells. This study provides valuable insights for the development of efficient drug delivery systems based on liposome-cell fusion strategies.
Article
Chemistry, Multidisciplinary
Eduard O. Bobylev, Ye Zeng, Kevin Weijgertse, Emma Koelman, Eline M. Meijer, Bas de Bruin, Alexander Kros, Joost N. H. Reek
Summary: By introducing M12L24 cages as siRNA delivery agents, we successfully prepared stable 130 nm nanocage/siRNA assemblies and achieved cell-specific siRNA delivery and silencing effects based on the choice of metal used for nanocage formation. The ability to tune the delivery efficiency and stability of nanocages by different building blocks and metals shows potential for future siRNA delivery applications.
Article
Medicine, Research & Experimental
Oscar Escalona-Rayo, Ye Zeng, Renzo A. Knol, Thomas J. F. Kock, Dennis Aschmann, Bram Slutter, Alexander Kros
Summary: This study examined the effects of three clinically-approved ionizable cationic lipids (ICLs) on the performance of lipid nanoparticles (LNPs) for mRNA delivery and vaccine efficacy. The results showed differences in the in vitro and in vivo performance of LNPs containing different ICLs, suggesting that in vitro data may not adequately predict their behavior in vivo.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Allergy
Hans Warmenhoven, Romain Leboux, Athanasios Bethanis, Jolinde van Strien, Adrian Logiantara, Hans van Schijndel, Lorenz Aglas, Leonie van Rijt, Bram Sluetter, Alexander Kros, Wim Jiskoot, Ronald van Ree
Summary: This study evaluated allergen-bearing liposomes as a possible alternative to aluminum hydroxide (alum) in subcutaneous allergen immunotherapy (SCIT). The results showed that these nanoparticles exhibited hypo-allergenic properties, induced a strong humoral immune response, and promoted IL-10 production, making them a promising alternative to alum-adsorption of allergens used in SCIT.
FRONTIERS IN ALLERGY
(2023)
Article
Biochemistry & Molecular Biology
Etienne J. Slapak, Mouad el Mandili, Marieke S. Ten Brink, Alexander Kros, Maarten F. Bijlsma, C. Arnold Spek
Summary: Pancreatic adenocarcinoma (PDAC) is difficult to treat with chemotherapy and has a poor survival rate. Targeted drug delivery approaches using mesoporous silica nanoparticles (MSNs) have shown promise in killing PDAC cells in vitro. However, when tested in clinically relevant models, off-target toxicity was observed. Optimized ADAM9-responsive MSNs (OPT-MSNs) were developed to minimize off-target cytotoxicity while still efficiently killing PDAC cells. In a preclinical PDAC xenograft model, paclitaxel-loaded OPT-MSNs reduced organ damage and leukopenia but did not exhibit antitumor activity. This study highlights the challenges in translating MSN-based tumor-targeting strategies into effective clinical treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Eduard O. Bobylev, Renzo A. Knol, Simon Mathew, I. I. I. David A. Poole, Ioli Kotsogianni, Nathaniel I. Martin, Bas de Bruin, Alexander Kros, Joost N. H. Reek
Summary: There is a growing interest in using metal-organic cages (MOCs) in the field of biomedicine due to their unique distribution in organisms and novel cytotoxicity mechanisms. However, the stability of many MOCs under in vivo conditions hinders their study in living cells. In this study, the toxicity and photophysical properties of stable rhodamine-functionalized platinum-based Pt2L4 nanospheres and their building blocks are investigated in vitro and in vivo. The results show that the Pt2L4 nanospheres exhibit reduced cytotoxicity and altered biodistribution compared to the building blocks in zebrafish and human cancer cell lines. These findings provide a basis for the application of MOCs in cancer therapy.
Article
Chemistry, Physical
Guus van der Borg, Niek Crone, Aimee L. Boyle, Alexander Kros, Wouter H. Roos
Summary: Membrane fusion is crucial for life and can be studied using artificial fusion peptides. This study investigated the efficiency and kinetics of two fusion peptides, CPE and CPK, using TIRF microscopy. The authors found that the fusogenic facilitation of CPE and CPK in liposomes is dependent on the particle size, and CPK alone can facilitate membrane fusion in certain conditions. These findings provide insights into peptide-mediated membrane fusion and have implications for drug delivery systems.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Multidisciplinary
Ye Zeng, Mengjie Shen, Roy Pattipeiluhu, Xuequan Zhou, Yun Zhang, Thomas Bakkum, Thomas H. Sharp, Aimee L. Boyle, Alexander Kros
Summary: Gene delivery has great potential for treating diseases, but the current lipid nanoparticle delivery systems are inefficient. This study proposes a highly efficient gene delivery system using fusogenic coiled-coil peptides, which can bypass the issue of endosomal escape.