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Cellular and Molecular Pathobiology of Cardiovascular Disease - 1st Edition - ISBN: 9780124052062, 9780124055254

Cellular and Molecular Pathobiology of Cardiovascular Disease

1st Edition

Editors: Monte Willis Jonathon Homeister James Stone
eBook ISBN: 9780124055254
Hardcover ISBN: 9780124052062
Imprint: Academic Press
Published Date: 23rd December 2013
Page Count: 338
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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







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


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




No. of pages:
© Academic Press 2014
23rd December 2013
Academic Press
eBook ISBN:
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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


"The images and illustration quality are exceptional, with a plethora of molecular and biochemical information related to each topic. Readers looking for a detailed reference for participation in research or for a presentation will find this a great resource. Rating: 3 Stars"--Doody', September 5 2014 

"…designed to complement standard anatomic cardiovascular textbooks by discussing some areas that are not usually included in them. Among the topics are: the molecular basis of cardiac development; cardiac atrophy and remodeling; the pathophysiology of cardiac hypertrophy and heart failure; ischemic heart disease and its consequences…", April 2014

Ratings and Reviews