Cellular and Molecular Pathobiology of Cardiovascular Disease

Cellular and Molecular Pathobiology of Cardiovascular Disease

1st Edition - December 23, 2013

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  • Editors: Monte Willis, Jonathon Homeister, James Stone
  • eBook ISBN: 9780124055254
  • Hardcover ISBN: 9780124052062

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Cellular and Molecular Pathobiology of Cardiovascular Disease focuses on the pathophysiology of common cardiovascular disease in the context of its underlying mechanisms and molecular biology. This book has been developed from the editors' experiences teaching an advanced cardiovascular pathology course for PhD trainees in the biomedical sciences, and trainees in cardiology, pathology, public health, and veterinary medicine. No other single text-reference combines clinical cardiology and cardiovascular pathology with enough molecular content for graduate students in both biomedical research and clinical departments. The text is complemented and supported by a rich variety of photomicrographs, diagrams of molecular relationships, and tables. It is uniquely useful to a wide audience of graduate students and post-doctoral fellows in areas from pathology to physiology, genetics, pharmacology, and more, as well as medical residents in pathology, laboratory medicine, internal medicine, cardiovascular surgery, and cardiology.

Key Features

  • Explains how to identify cardiovascular pathologies and compare with normal physiology to aid research
  • Gives concise explanations of key issues and background reading suggestions
  • Covers molecular bases of diseases for better understanding of molecular events that precede or accompany the development of pathology


Cardiovascular researchers and non-cardiovascular researchers working in peripheral areas; practicing clinicians (non-cardiologists); graduate students and post-doctoral fellows in a wide array of biomedical departments (e.g. pathology, physiology, genetics, pharmacology, public health, molecular biology, cell biology) related to the CV sciences curricula, as well as medical residents in pathology, laboratory medicine, internal medicine, cardiovascular surgery, and cardiology.

Table of Contents

  • Dedication






    Chapter 1. Molecular Basis of Cardiac Development



    The Heart Fields and Heart Tube Formation

    Looping and laterality

    Chamber Specification

    Ventricular Septation and Myocardial Patterning

    Conduction System Development

    Valve Development

    Atrial Septation

    Arterial Pole Maturation

    Epicardial and Coronary Vascular Development



    Chapter 2. Cardiac Metabolism in Health and Disease



    Energy Availability

    Major Sources of Energy

    Energy Expenditure: Work of the Heart

    Pathological Alterations in Myocardial Energy Metabolism

    Metabolism of Heart Failure

    Mitochondrial Mechanisms in Heart Disease


    Chapter 3. Cardiac Atrophy and Remodeling


    Overview of Atrophic Cardiac Remodeling

    Models of Atrophic Remodeling

    Cardiac Workload Determines Cardiac Size

    Morphological Features of the Atrophic Heart

    Extracellular Matrix Remodeling with Cardiac Atrophy

    Protein Homeostasis in the Healthy and Atrophic Heart

    Metabolic Unloading of the Myocardium

    Signaling Pathways Activated During Cardiac Atrophy

    Molecular Alterations in Atrophic Remodeling: The Fetal Gene Program

    Contractile Function in Cardiac Atrophy

    Regulation of Atrophic Remodeling by MICRORNAs

    Atrophic Remodeling due to Cardiac Pathology

    Atrophic Remodeling as a Potential Therapeutic



    Chapter 4. The Pathophysiology of Cardiac Hypertrophy and Heart Failure



    Etiology of Heart Failure

    Physiologic Hypertrophy

    Pathologic Hypertrophy

    Molecular Mechanisms of Pathologic LVH


    Chapter 5. Ischemic Heart Disease and its Consequences



    Pathophysiology of Ischemia–Reperfusion Injury

    Therapeutic Strategies to Combat Myocardial Ischemia–Reperfusion Injury

    Clinical Trial Failure

    Summary and Concluding Remarks


    Chapter 6. Pathophysiology of Cardiomyopathies



    Dilated Cardiomyopathy

    Ischemic Cardiomyopathy

    Idiopathic Dilated Cardiomyopathy

    Chagas Disease-Related Cardiomyopathy

    Alcoholic Cardiomyopathy

    Peripartum Cardiomyopathy

    Hypertrophic Cardiomyopathy

    Restrictive Cardiomyopathy

    Anderson-Fabry’s Cardiomyopathy

    Cardiac Hemosiderosis

    Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

    Left Ventricular Non-Compaction Cardiomyopathy

    Role Of Genetic Testing and Future Directions


    Chapter 7. Cellular and Molecular Pathobiology of the Cardiac Conduction System


    Overview of the Cardiac Conduction System

    The Sinoatrial Node

    The Atrioventricular Node

    Bundle of His and Bundle Branches

    Cardiac Purkinje Fibers

    Role of Autonomic Nervous System

    Human Conduction System Disease

    MicroRNAs and Cardiac Conduction


    Chapter 8. Molecular Pathobiology of Myocarditis





    Pathogenic Mechanisms


    Consensus Statement on EMB from the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology


    Chapter 9. Calcific and Degenerative Heart Valve Disease



    Normal Valve Function, Biomechanics, and Structure

    Valve Development, Post-Developmental Adaptation, and Aging

    Calcific Aortic Valve Disease (CAVD)

    Mechanisms of CAVD

    Animal Models of CAVD

    Degenerative Mitral Valve Disease (DMVD)

    Mechanisms of DMVD

    Animal Models of Mitral Valve Disease

    Future Research Opportunities in Heart Valve Disease: Key Questions


    Chapter 10. Vasculogenesis and Angiogenesis



    Vascular Development

    Developmental Abnormalities

    Angiogenic Component of Pathologies


    Chapter 11. Diseases of Medium-Sized and Small Vessels



    Normal Vessel Wall Structure

    Vascular Cell Activation

    Intimal Hyperplasia

    Diabetic Vasculopathy

    Amyloid Vasculopathy

    Small Vessel Vasculitis

    KAWASAKI Disease

    Giant Cell Arteritis

    Vascular Trauma and the Hypothenar Hammer Syndrome

    Vasospasm and Raynaud’s Phenomenon


    Chapter 12. Pathophysiology of Atherosclerosis



    Early Lesions

    Lipids in Atherosclerosis

    Endothelial Activation

    Inflammation in Atherosclerosis

    The Atherosclerotic Plaque

    Aortic Atherosclerosis and Atherosclerotic Aneurysms

    The Genetics of Atherosclerosis

    Clinical Implications

    Laboratory and Animal Models



    Chapter 13. Genetic Diseases of the Aorta (Including Aneurysms)


    The Normal Aorta: Histology and Function

    Gross Pathologic Changes to the Aorta

    Demographics of Aneurysms and Dissections

    Histopathologic Changes to the Aorta

    Specific Genetic Syndromes and Causes of Aneurysm

    Non-Genetic Causes of Aortic Aneurysm

    Evidence for the TGF-β Pathway to be a Unifying Mechanism of Aortic Aneurysm

    TGF-β Canonical and Non-Canonical Signaling in the Ascending Aorta

    TGF-β Signaling in Ascending Aortic Diseases

    TGF-β Signaling in the Descending Aorta

    Biomarkers of Aneurysm

    Treatment for Aneurysm

    Future Directions


    Chapter 14. Blood Pressure Regulation and Pathology




    Definition of Essential (Primary) Hypertension

    Genetics of Hypertension

    Physiological Control of Blood Pressure

    Cardiac Output and Hypertension

    The Sympathetic Nervous System and Hypertension

    The Kidney and Hypertension

    Sodium and Hypertension

    The Renin–Angiotensin System (RAS)

    Angiotensin Receptors and Signaling

    The Vascular System and Hypertension

    Reactive Oxygen Species, Oxidative Stress, and Human Hypertension

    New Drugs, Procedures, and Devices in the Management of Hypertension



    Chapter 15. Venous and Arterial Thrombosis



    Venous Thrombosis

    Arterial Thrombosis


    Chapter 16. The Pericardium and its Diseases


    The Pericardium and its Diseases

    Serological Tests


    Pericardiocentesis and Biopsy

    Specific Forms of Pericarditis



Product details

  • No. of pages: 338
  • Language: English
  • Copyright: © Academic Press 2014
  • Published: December 23, 2013
  • Imprint: Academic Press
  • eBook ISBN: 9780124055254
  • Hardcover ISBN: 9780124052062

About the Editors

Monte Willis

Monte Willis
Monte S. Willis, MD, PhD, MBA is Vice-Chair of Academic Affairs and Associate Professor in the Department of Pathology and Laboratory Medicine at the Univeristy of North Carolina-Chapel Hill. He is Director of Campus Health Services Laboratory and the McLendon Clinical Laboratories and principal investigator in the McAllister Heart Institute, where he leads a research team studying the role of the ubiquitin proteasome system in metabolism and the pathophysiology of cardiac disease (supported by NIH and the Fondation Leducq) and teaches in the School of Medicine and Graduate School. Dr. Willis received his combined MD and PhD training at the University of Nebraska Medical Center. He went on to complete a residency in the Department of Pathology and post-doctoral training in in Burns, Trauma, and Critical Care in the Department of Surgery at the University of Texas Southwestern Medical Center. He has received multiple honors for his research, including the Cotran Early Career Investigator Award from the American Society of Investigative Pathology, and the Jefferson-Pilot Fellowship in Academic Medicine from the University of North Carolina School of Medicine. He is active on the editorial boards of the American Journal of Pathology, Cardiovascular Pathology, Journal of Molecular and Cellular Cardiology, American Journal of Physiology-Endocrine and Metabolism and co-chairs an American Heart Association Study Section. Dr. Willis has published more than 210 manuscripts in clinical, translational, and the basic sciences and edited multiple medical textbooks, including Molecular and Translational Vascular Medicine (2012); Translational Cardiology: Molecular Basis of Cardiac Metabolism, Cardiac Remodeling, Translational Therapies, and Imaging Techniques (2012), and the Cellular and Molecular Pathobiology of Cardiovascular disease (2013).

Affiliations and Expertise

University of North Carolina, Chapel Hill, NC, USA

Jonathon Homeister

Jonathon Homeister
Jonathon W. Homeister earned Bachelor of Arts degrees in Biology and Chemistry in 1985 from Hope College, where he began his research endeavors mentored by Christoper C. Barney, Ph.D. He then earned the Doctor of Philosophy in Pharmacology, mentored by Benedict R. Lucchesi, M.D., Ph.D., and the Doctor of Medicine from the University of Michigan in 1993. He received residency training in anatomic pathology at the University of Michigan Hospitals and is a Diplomat of the American Board of Pathology. After residency, he received additional research training as an Associate of the Howard Hughes Medical Institute, mentored by John B. Lowe, M.D. He is currently an Associate Professor in the Department of Pathology and Laboratory Medicine, and member of the McAllister Heart Institute at the University of North Carolina at Chapel Hill, where he is also Director of the Molecular and Cellular Pathology Graduate Program. His clinical interests include cardiovascular, autopsy, and forensic pathology, and his research interests focus on the glycobiology inherent to leukocyte trafficking, with particular respect to the pathogenesis of cardiovascular diseases including atherosclerosis and thrombosis.

Affiliations and Expertise

University of North Carolina, Chapel Hill, USA

James Stone

James Stone
Dr. Stone graduated summa cum laude from Wabash College with a B.A. in chemistry. He then completed the Medical Scientist Training Program at the University of Michigan where he earned both an MD and a PhD in Biological Chemistry. His doctoral thesis research was performed in the laboratory of Prof. Michael A. Marletta, where he purified and characterized the sensor for nitric oxide, the soluble form of guanylate cyclase.

Dr. Stone completed the Anatomic Pathology Residency Program at Brigham and Women’s Hospital and Harvard Medical School. Dr. Stone completed clinical fellowship training in Cardiovascular Pathology at BWH under Prof. Frederick Schoen. He also completed post-doctoral research on endothelial cell biology in the Vascular Research Division at BWH and at Children’s Hospital with Prof. Tucker Collins.

Dr. Stone is currently Head of the Cardiovascular Pathology Service and Director of the Autopsy Service at Massachusetts General Hospital. He is also an Associate Professor of Pathology at Harvard Medical School. Dr. Stone directs a research laboratory in the Center for Systems Biology at MGH studying mechanisms underlying cardiovascular diseases. His group has particular focus on vascular cell activation, vasculitis and atherosclerosis, and on bridging the gap between model systems and human cardiovascular diseases.

Affiliations and Expertise

Harvard Medical School, Boston, MA, USA

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