Article
Multidisciplinary Sciences
Tomoya Sasahara, Kaori Satomura, Mari Tada, Akiyoshi Kakita, Minako Hoshi
Summary: The study found that amyloid beta-protein (A beta) plays an important role in Alzheimer's disease (AD), contributing to its worsening through vascular dysfunction. It was discovered that patient-derived A beta assemblies (ASPD) inhibit vasorelaxation by binding to the alpha 3 subunit of sodium, potassium-ATPase (NAK alpha 3), leading to neurodegeneration in neurons.
Article
Cardiac & Cardiovascular Systems
Kaveeta Kaw, Abhijnan Chattopadhyay, Pujun Guan, Jiyuan Chen, Suravi Majumder, Xue-yan Duan, Shuangtao Ma, Chen Zhang, Callie S. Kwartler, Dianna M. Milewicz
Summary: This study investigates how the variant p.Arg149Cys in ACTA2 gene predisposes to atherosclerosis in individuals without cardiovascular risk factors. The variant increases intracellular cholesterol levels in smooth muscle cells, leading to atherosclerotic plaque formation. Treatment with the HMG-CoAR inhibitor pravastatin successfully reverses the increased plaque burden.
EUROPEAN HEART JOURNAL
(2023)
Article
Cell Biology
Xiuli Mao, Yiling Tan, Huali Wang, Song Li, Yue Zhou
Summary: This study suggests that substrate stiffness plays a significant role in regulating cholesterol accumulation in smooth muscle cells (SMCs). Higher cholesterol accumulation was observed on substrates with either low (1 kPa) or high (100 kPa) stiffness, compared to intermediate stiffness at 40 kPa. The expression of cholesterol efflux gene ABCA1 was found to be higher on the 40 kPa substrate, and treatment with LXR agonist GW3965 increased ABCA1 expression and reduced cholesterol loading in SMCs. Specifically, knockdown of ABCA1 gene resulted in increased cholesterol accumulation in SMCs on substrates with different stiffnesses.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Hematology
Abhijnan Chattopadhyay, Callie S. Kwartler, Kaveeta Kaw, Yanming Li, Anita Kaw, Jiyuan Chen, Scott A. LeMaire, Ying H. Shen, Dianna M. Milewicz
Summary: The study found that vascular smooth muscle cells undergo phenotypic switching and express macrophage and fibroblast markers under cholesterol exposure. This switching is associated with the activation of the endoplasmic reticulum unfolded protein response, and blocking this response prevents the phenotypic transition.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lena Kappert, Philipp Ruzicka, Anton Kutikhin, Carolina De la Torre, Andreas Fischer, Markus Hecker, Caroline Arnold, Thomas Korff
Summary: NFAT5 plays a crucial role in regulating cholesterol efflux in vascular smooth muscle cells (VSMCs) adjacent to arteriosclerotic plaques, and its loss may lead to cholesterol accumulation and inhibition of genes involved in lipid handling and oxidative stress management. The absence of Nfat5 in VSMCs contributes to the development of lipid-laden arterial lesions and promotes pro-atherogenic responses in the vasculature.
Article
Biochemistry & Molecular Biology
Alexander G. Bobylev, Elmira Yakupova, Liya G. Bobyleva, Nikolay Molochkov, Alexander A. Timchenko, Maria A. Timchenko, Hiroshi Kihara, Alexey D. Nikulin, Azat G. Gabdulkhakov, Tatiana N. Melnik, Nikita Penkov, Michail Y. Lobanov, Alexey S. Kazakov, Miklos Kellermayer, Zsolt Martonfalvi, Oxana Galzitskaya, Ivan M. Vikhlyantsev
Summary: The giant protein titin, found in striated and smooth muscles, undergoes nonspecific amyloid aggregation in vitro. The high-molecular-weight isoform of chicken smooth-muscle titin forms amorphous amyloid aggregates with a quaternary cross-beta structure. These aggregates do not affect the secondary structure of the protein and can partially disaggregate at higher ionic strengths. This study suggests that specific domains/segments of titin are involved in the amyloid aggregation process. Understanding amyloidogenesis could be expanded by studying titin as an object of interest.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Hyun-Jung Kim, Paul Cheng, Stanislao Travisano, Chad Weldy, Joao P. Monteiro, Ramendra Kundu, Trieu Nguyen, Disha Sharma, Huitong Shi, Yi Lin, Boxiang Liu, Saptarsi Haldar, Simon Jackson, Thomas Quertermous
Summary: Genes encoding risk for coronary disease are crucial for developing new therapies. A particular gene, PDGFD, has been identified as a culprit gene and it promotes disease risk. Mechanistic studies confirm that rs2019090 and PDGFD represent the functional genetic variant and gene responsible for coronary artery disease. PDGFD mediates CAD risk by promoting deleterious phenotypic changes in smooth muscle cells and an inflammatory response primarily focused in the adventitia.
NATURE COMMUNICATIONS
(2023)
Article
Cardiac & Cardiovascular Systems
Xiong Jia, Zongtao Liu, Yixuan Wang, Geng Li, Xiangli Bai
Summary: This study found that serum amyloid A (SAA) and interleukin-1 beta (IL-1β) play important roles in the transcytosis of low density lipoproteins (LDL) and the development of atherosclerosis. SAA and IL-1β accelerate LDL transcytosis across endothelial cells via the NF-kappa B/caveolin-1/cavin-1 pathway, leading to inflammation in the arterial intima. Furthermore, SAA and IL-1β promote the formation of lipid-rich atherosclerotic lesions in the aorta.
Article
Hematology
Joshua A. Dubland, Sima Allahverdian, Katrina J. Besler, Carleena Ortega, Ying Wang, Collin S. Pryma, Kamel Boukais, Teddy Chan, Michael A. Seidman, Gordon A. Francis
Summary: The study found that the inherently low level of LAL in SMCs compared with macrophages is associated with reduced capacity to catabolize atherogenic lipoproteins, which is a mechanism for SMC foam cell formation in atherosclerosis.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shuai Wang, Xiaoning Liu, Zeqi Meng, Qi Feng, Yanling Lin, Honglin Niu, Chao Yu, Yanhong Zong, Lingling Guo, Weiwei Yang, Yuehua Ma, Wenjun Zhang, Chenyang Li, Yunran Yang, Wenjuan Wang, Xurui Gao, Yaxin Hu, Chao Liu, Lei Nie
Summary: DCBLD2 is a transmembrane protein that regulates PDGFR-beta endocytosis, and its inhibition of receptor endocytosis can regulate the phenotypic conversion of VSMCs and arterial wall proliferation, making it a potential therapeutic target for cardiovascular diseases.
Article
Cardiac & Cardiovascular Systems
Zixuan Tian, Min Liu, Ziying Zhang, Tao Yan, Shuyi Guo, Yu Miao, Jingyu Wang, Ru Zhang, Yanqing Bi, Nan Zhang, Xingguang Zhang
Summary: This study found an association between low-density lipoprotein cholesterol (LDL-C) levels and the risk of intracerebral hemorrhage (ICH). Low cholesterol levels may induce smooth muscle cell necrosis by inhibiting the autophagy pathway, thereby increasing the risk of ICH.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Alessandra Galli, Anoop Arunagiri, Nevia Dule, Michela Castagna, Paola Marciani, Carla Perego
Summary: Pancreatic beta-cells play a crucial role in glucose homeostasis by secreting insulin, and their dysfunction leads to diabetes. Cholesterol has gained significant attention as it not only controls beta-cell function but is also targeted by lipid-lowering therapies for diabetes-related cardiovascular complications. Understanding the mechanisms of cholesterol-mediated beta-cell function is still an area of exploration. Studies suggest that beta-cells regulate both total cholesterol levels and its distribution within organelles through vesicular and non-vesicular transport. This review aims to summarize the current understanding of cholesterol homeostasis in beta-cells and provide insights into the dynamic distribution of cholesterol among organelles to maintain their functionality, with a focus on early steps of insulin synthesis and secretion.
Article
Biochemistry & Molecular Biology
Matthew Stephens, Simon Roizes, Pierre-Yves von der Weid
Summary: The study found that Lovastatin and Simvastatin have concentration-dependent effects on the contractility of intestinal lymphatic vascular smooth muscle, which are related to their structural characteristics. Lovastatin acts by increasing the function of RhoKinase, while Simvastatin results in mitochondrial depolymerization in lymphatic smooth muscle cells, affecting their function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Vladimir Rudajev, Jiri Novotny
Summary: This article discusses the relationship between cholesterol and the development of Alzheimer's disease, as well as the influence of cholesterol on the production of amyloid beta (Aβ).
CELL AND BIOSCIENCE
(2023)
Article
Clinical Neurology
Martina Pannuzzo
Summary: Despite continuous worldwide efforts, clinical trials for Alzheimer's disease (AD) therapeutics have not been successful. There is a new concept suggesting that the amyloid-beta (Aβ) peptide may modulate synaptic plasticity and protect against excitotoxicity, challenging the previous belief that it is a major contributor to AD pathogenesis. The relationship between Aβ-mediated synaptic plasticity and trafficking remains complex and controversial, indicating a need for further research.
ALZHEIMERS & DEMENTIA
(2022)
Article
Multidisciplinary Sciences
Stephanie E. Seidl, Lawrence G. Pessolano, Christopher A. Bishop, Michael Best, Celeste B. Rich, Phillip J. Stone, Barbara M. Schreiber
Article
Biochemistry & Molecular Biology
Paola A. Hurtado, Siddharth Vora, Siddika Selva Sume, Dan Yang, Cynthia St. Hilaire, Ying Guo, Amitha H. Palamakumbura, Barbara M. Schreiber, Katya Ravid, Philip C. Trackman
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2008)
Article
Biophysics
Lauren D. Black, Philip G. Allen, Shirley M. Morris, Phillip J. Stone, Bela Suki
BIOPHYSICAL JOURNAL
(2008)
Article
Biochemistry & Molecular Biology
Christopher P. Sullivan, Stephanie E. Seidl, Celeste B. Rich, Michel Raymondjean, Barbara M. Schreiber
JOURNAL OF BIOLOGICAL CHEMISTRY
(2010)
Article
Biophysics
Brett C. Isenberg, Daniel E. Backman, Michelle E. Kinahan, Rajiv Jesudason, Bela Suki, Phillip J. Stone, Elaine C. Davis, Joyce Y. Wong
JOURNAL OF BIOMECHANICS
(2012)
Article
Biochemistry & Molecular Biology
Cynthia St. Hilaire, Dan Yang, Barbara M. Schreiber, Katya Ravid
JOURNAL OF CELLULAR BIOCHEMISTRY
(2008)
Article
Multidisciplinary Sciences
Dan Yang, Milka Koupenova, Donald J. McCrann, Katherine J. Kopeikina, Herbert M. Kagan, Barbara M. Schreiber, Katya Ravid
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2008)
Article
Multidisciplinary Sciences
Michael C. Ritter, Rajiv Jesudason, Arnab Majumdar, Dimitrije Stamenovic, Jo Ann Buczek-Thomas, Phillip J. Stone, Matthew A. Nugent, Bela Suki
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2009)
Article
Multidisciplinary Sciences
Frank Guarnieri, Jean L. Spencer, Edgar C. Lucey, Matthew A. Nugent, Phillip J. Stone
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2010)
Article
Pharmacology & Pharmacy
Yinzhi Zhao, Lijun Chen, Song Gao, Paul Toselli, Phillip Stone, Wande Li
Article
Dentistry, Oral Surgery & Medicine
Theresa A. Davies, Elizabeth Kaye, Michele Stahlberger, Majed Abbas, Catherine Sarkis, Linda Reed, Larry Dunham, Barbara M. Schreiber, Cataldo Leone, Ana Karina Mascarenhas
JOURNAL OF DENTAL EDUCATION
(2019)
Article
Toxicology
Denise K. Chou, Yinzhi Zhao, Song Gao, Iih-Nan Chou, Paul Toselli, Phillip Stone, Wande Li
TOXICOLOGICAL SCIENCES
(2007)