Cholesterol Crystals in Atherosclerosis and Other Related Diseases
ISBN-13: 9783031411915 / Angielski / Twarda / 2023
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This book is the first authoritative and comprehensive text dedicated to the understanding of how cholesterol triggers vascular inflammation and mechanical injury that leads to heart attacks, strokes as well as other organ and tissue pathology. It includes chapters on the background of cholesterol crystal formation and methods for their detection as well as a description of the physiochemical transformation of metastable ‘liquid’ cholesterol to a solid flat plate crystalloid within the cellular and extracellular environment resulting in volume expansion. Chapters also discusses cholesterol crystals and other crystalloid molecules found in atherosclerotic plaque. In addition, the book examines how cholesterol crystals can induce similar injurious processes in other organs including the retina of the eye to cause blindness, in solid cancers causing further tumor growth and in the brain of patients with Alzheimer’s. And lastly, the book addresses various potential therapeutics that disrupt the physiochemical transformation of cholesterol from a liquid to a solid, inhibit its role in triggering inflammation and tissue injury while ushering a path towards targeted therapies.
Cholesterol Crystals in Atherosclerosis and Other Related Diseases will be of interest to cardiologists as well as individuals in various fields of science including crystallography, basic and clinical imaging, cardiac oncology, and drug discovery.
1. George S Abela, MD, MSc, Department of Medicine/Cardiology, Michigan State University, East Lansing, MI.
2. Yvonne Baumer, PhD National Heart Lung and Blood Institute, Univ of Hawaii.
3. Julia Busik, PhD Professor of Physiology, Michigan State University, East Lansing, MI
4. Harvey Bumpers, MD Department of Surgery/Cancer surgery, Michigan State University, East Lansing, MI
5. Howard Chen, MD Neuropathologist Sparrow Hospital, East Lansing, MI
6. Martin Crimp, PhD Professor, Department of Chemical Engineering & Material Science, Michigan State University, East Lansing, MI
7. Jiannan Dai, MD Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
8. Sergio Fazio, MD, Phd, Professor of Medicine OHSU. Director, Center for Preventive Cardiology
9. Stanley Flegler PhD Director Advanced Microscopy, Michigan State University, E Lansing, MI
10. Kathleen Gallo, PhD. Professor of Physiology, Department of Physiology, Michigan State University, East Lansing, MI
11. Maria Grant, MD Professor of Medicine, University of Alabama, Birmingham, Alabama
12. James Hamilton, PhD Professor and Director BU High Field MRI Core Boston University School of Medicine Dept of Physiology and Biophysics
13. Kanaan PhD neuroscience, Michigan State University, Grand Rapids, MI
14. Kazuhisa Kodama MD., PhD. The Osaka Police Hospital 〒543-0035, 10-31, kitayama-cho, Tennoji-ku, Osaka-city, Japan
15. Sei Komatsu MD., PhD. The Osaka Police Hospital 〒543-0035, 10-31, kitayama-cho, Tennoji-ku, Osaka-city, Japan
16. Howard Kruth, MD Scientist Emeritus, National Institutes of Health, Bethesda, MD
17. Eike Latz, MD, PhD University of Bonn, Bonn, Germany
18. Preston Mason, PhD Harvard Medical School, Brigham and Women’s Cellular Work, Boston, MA
19. Sabhash Mitra, MD Associate Professor of Medicine, Infectious Diseases, Michigan State University, EL, MI
21. Stefan Mark Nidorf, MD The Heart & Vascular Research Institute of Sir Charles Gairdner Hospital, GenesisCare Western Australia, Perth, Australia.
22. Eric Potma, PhD Professor of Chemistry, University of CA, Irvine, CA
23. Chunqi Qian, PhD MRI, Visiting professor, Nanjing University, China
24. Paul Ridker, MD, Senior Physician, Brigham and Women’s Hospital. Harvard Medical School.
25. James Richard, DO, Chair Department of Pathology, Sparrow, Hospital, Lansing, MI
26. Mathew Steensma, MD Orthopedic Oncology, Spectrum, Grand Rapids, MI
27. Guillermo J Tearney, MD Professor of pathology, Harvard Medical School, Mass Gen Hospital
28. Abigail Vandenberg, BSc Scanning Electron Microscopy, Michigan State University, E Lansing, MI
29. Lia Addadi PhD and Neta Versano, PhD Weizmann Institute, Israel.
30. Xuefei Huang, PhD Professor of Chemistry, Michigan State University East Lansing, MI.
George S. Abela, M.D., M.Sc., M.B.A.
Michigan State University
Department of Medicine, Cardiology
B208 Clinical Center, East Lansing, MI 48824
Phone: 517-353-1754; Fax: 517-353-4978;
email: abela@msu.edu
Stefan Mark Nidorf, M.B.B.S., F.R.A.C.P., M.D.
Cardiologist
Sir Charles Gairdner Hospital
The Heart and Vascular Research Institute
3/140 Mount Bay Rd
Perth, Western Australia 6000
(61+) 4803000
smnidorf@gmaiol.com
George S. Abela is a physician scientist and chief of cardiology at Michigan State University. He has conducted and authored the seminal research describing for the first time the critical role of cholesterol crystals in tissue injury. This was accomplished by demonstrating that cholesterol expands in volume when transformed from a liquid to solid state generating the hypothesis that this expansion in the confined environment of an atherosclerotic plaque can lead to rupture and erosion. Support data comes from demonstration of extensive crystals perforating ruptured plaques only in patients who died with myocardial infarction. Moreover, by modifying the tissue preparation process that avoids ethanol for scanning electron microscopy, he and lab co-workers were able to preserve the crystals from being dissolved by ethanol dehydration, a protocol that had been established centuries earlier. This unraveled the extent and severity of mechanical injury to the arterial wall by sharp tipped cholesterol crystals. He demonstrated that this process is not only present in coronary artery atherosclerotic plaques but also in cardiac valves, various solid cancers, brains from Alzheimer patients and most recently was found by other investigators in diabetic retinopathy. This universal process is a source of inflammation triggered by the transformation of cholesterol as a metastable molecule into a flat crystal. In a collaboration between Dr. Abela and immunologists, they demonstrated the role of cholesterol crystals in triggering inflammation via the NLRP3 inflammasome similar to the mechanism described for uric acid crystals. Overall, atherosclerosis as a crystalloid disease was recognized based on the discoveries made in Dr. Abela’s laboratory at Michigan State University.
Stefan Mark Nidorf is a clinical cardiologist practicing in Perth Western Australia affiliated the Heart and Vascular Research Institute at the Perkins Research Institute. His clinical research interest in atherosclerosis led him to initiate the LoDoCo trials of low dose colchicine for the secondary prevention of chronic coronary disease, the rationale of which has been strengthened by an improved understanding of how cholesterol transitions from an essential molecule into a crystalline form that can act to initiate and perpetuate the chronic and acute manifestations of atherosclerosis.
This book is the first authoritative and comprehensive text dedicated to the understanding of how cholesterol triggers vascular inflammation and mechanical injury that leads to heart attacks, strokes as well as other organ and tissue pathology. It includes chapters on the background of cholesterol crystal formation and methods for their detection as well as a description of the physiochemical transformation of metastable ‘liquid’ cholesterol to a solid flat plate crystalloid within the cellular and extracellular environment resulting in volume expansion. Chapters also discusses cholesterol crystals and other crystalloid molecules found in atherosclerotic plaque. In addition, the book examines how cholesterol crystals can induce similar injurious processes in other organs including the retina of the eye to cause blindness, in solid cancers causing further tumor growth and in the brain of patients with Alzheimer’s. And lastly, the book addresses various potential therapeutics that disrupt the physiochemical transformation of cholesterol from a liquid to a solid, inhibit its role in triggering inflammation and tissue injury while ushering a path towards targeted therapies.
Cholesterol Crystals in Atherosclerosis and Other Related Diseases will be of interest to cardiologists as well as individuals in various fields of science including crystallography, basic and clinical imaging, cardiac oncology, and drug discovery.