Preface

The study of the structure and behavior of cardiomyocyte is fundamental to the education of all cardiologists because it is the bridge leading from basic science to clinical cardiology. The marked diversity of cells constituting the tissues and organs of the human body is known. There are more than 200 morphologically distinct adult cell types and this large number reflects the diversity of their function. However, despite this diversity of structure and function, there is a small range of structural subunits and organelles that comprise these cell types. A cell with a particular function will have a predictable constellation of organelles relating to that specialization. So, understanding the structure and function of normal heart cells lays the foundation for developing studies designed to explore the pathogenesis of diseased myocardium. Knowledge of the pathological basis of disease, with particular reference to causation, pathogenesis, and possible natural histories, is essential if the clinical manifestations of disease are to be interpreted and treated in a rational way.

Many pathological states can be represented as expression of disturbances in a normal dynamic equilibrium. Myocardial ischemia may represent a condition if the blood supply to the myocardium does not meet the demand. The energy requirements of heart muscle are high. If this disturbance in the normal equilibrium persists, it triggers a cascade of cellular, inflammatory, and biochemical events, leading to the death of cardiomyocytes. Contraction of cardiomyocytes and the maintenance of their membrane integrity require large amounts of energy. Heart muscle is poorly supplied with endogenous fuel stores, is well vascularized, and is highly aerobic in its metabolism. Interruptions to the blood supply of the myocardium, even for comparatively shorts periods, produce catastrophic results.

Generation, reception, and transduction of signals at an appropriate level are intrinsic to normal cell behavior. Serious functional disturbances may arise when the cells cannot generate or transport an appropriate signal or lack the appropriate receptors to receive an important signal. Intercellular communication is fundamental for normal cardiac function. Synchronization of mechanical and electrical activity is essential to transform the work of individual myocytes into the pumping function of the organ. Desmosome is a specialized adhesive junction that interacts with the cytoskeleton and creates interactions with gap and adherens junctions. Mutations in components of the desmosome lead to a variety of disorders such as arrhythmogenic cardiomyopathy, a disease that bridges the gap between inherited arrhythmia syndromes and heart muscle disorders.

In the introductory chapter, the author discusses the importance of understanding the molecular and cellular basis of cardiovascular disease. Knowledge of the pathological basis of disease with the integration of multilevel biological data and the connection with the clinical practice reveal the potential of personalized medicine, with future implications for prognosis, diagnosis, and management of cardiovascular diseases.

The authors of the second chapter investigate the molecular adaptation of right ventricular (RV) in response to left ventricular (LV) infarction. RV failure is common in patients with acute ST-segment elevated myocardial infarction and animal models of remodeling post-myocardial infarction. However, a systematic analysis of chamber-specific changes in the expression of genes linked to cardiac function, apoptosis, fibrosis, receptor responsiveness, and inflammation is lacking. The underlying reason for biventricular failure due to myocardial infarction and/ or transient ischemic events is not clear but may be a consequence of hemodynamic changes during infarction and ischemic events in the RV as well. Nevertheless, RV failure is a severe complication during the subsequent post-infarct period and a limitation to further prognosis.

Human physiological activity and condition during illness are under the control of the circadian rhythm. It is well known that many cardiovascular processes show daily variations depending on the circadian rhythm (blood pressure, heart rate), and the gene expression of the cardiomyocyte circadian clock influences myocardial contractile function, metabolism, and other gene expressions. The authors present a review of the latest knowledge on the impact of circadian rhythm and circadian rhythm genes on myocardial infarction.

The authors of the next chapter discuss the importance of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to investigate the mutationspecific mechanism. While animal models fail to recapitulate human cardiac disease phenotype properly, hiPSC-CMs have been successful in recapitulating crucial phenotypes of many genetic cardiac diseases in terms of morphology, contractility, Ca2+ handling, ion channel biophysics, cell signaling, and metabolism. Most strikingly, hiPSC-CMs provide the patient-specific platform to study the disease mechanism and drug response individually, which the traditional disease modeling technique would never offer. In addition, cardiac subtype-specific arrhythmias and drug screening could be performed with the help of an unlimited supply of hiPSC-CMs, thus chamber-specific treatment modalities could be identified. Certainly, by improving the current weaknesses of hiPSC-CMs, and incorporating with new gene-editing techniques, complex cardiac disease mechanisms could be deciphered and novel effective treatment therapies could be identified to improve the life of cardiac patients.

In the last decades, major advances have been made in the understanding of molecular and genetic issues, as well as in the pathophysiology and clinical assessment of cardiomyopathies. Especially, understanding the genetic basis of dilated cardiomyopathy (DCM) has improved considerably with the availability of genetic analysis. To further improve the prognosis of patients, it is important to regularly gather knowledge about the current state of DCM and adapt the appropriate diagnostic workups. Therefore, this chapter provides the reader with a comprehensive overview of the current state of DCM from definition over etiology, including the genetic aspects to management for cardiovascular specialists.

The following chapter is a review of myocardial changes associated with obesity. It is recognized that obesity contributes to cardiovascular and metabolic disorders through alterations in the levels of adipocyte-derived cytokines called adipokines. The authors conclude that, "our understanding of adipokine biology and obesityinduced adiposopathy increases, and the major challenge will reside in translating this information into new prognostic and therapeutic approaches to limit cardiovascular risk in obese individuals."

**V**

the age of 50.

Higher intakes of industrially produced trans-fatty acids (IP-TFAs) and of saturated fatty acids are associated with increased risk for congenital heart disease (CHD), and higher intakes of both the ω6 (n-6) polyunsaturated fatty acids (PUFAs) and the omega-3 PUFAs are associated with a lower risk of CHD. Since estimation of dietary intakes of fatty acids (FAs) using questionnaires is challenging (because of out-of-date databases, reliance on memory, poor estimation of portion sizes, etc.), many researchers have begun to measure plasma/blood levels of FAs as more objective biomarkers of exposure. The two general classes of FAs for which biomarkers are most strongly linked with intakes are PUFAs (especially the omega-3 class) and IP-TFAs. Because risk for CHD is much lower in Japan than in the USA, the authors undertook this study to compare the FA profiles in Japanese and American men over

I wish to thank the authors who have contributed so generously to this book. They are all experts in their fields of interest, but have taken time to write on their

> **Angelos Tsipis, MD, PhD, MSc** Department of Cardiology, Onassis Cardiac Surgery Centre,

National and Kapodistrian University of Athens,

Department of Pathology,

Athens, Greece

Medical School,

Athens, Greece

subjects to make this work as comprehensive as possible.

Higher intakes of industrially produced trans-fatty acids (IP-TFAs) and of saturated fatty acids are associated with increased risk for congenital heart disease (CHD), and higher intakes of both the ω6 (n-6) polyunsaturated fatty acids (PUFAs) and the omega-3 PUFAs are associated with a lower risk of CHD. Since estimation of dietary intakes of fatty acids (FAs) using questionnaires is challenging (because of out-of-date databases, reliance on memory, poor estimation of portion sizes, etc.), many researchers have begun to measure plasma/blood levels of FAs as more objective biomarkers of exposure. The two general classes of FAs for which biomarkers are most strongly linked with intakes are PUFAs (especially the omega-3 class) and IP-TFAs. Because risk for CHD is much lower in Japan than in the USA, the authors undertook this study to compare the FA profiles in Japanese and American men over the age of 50.

I wish to thank the authors who have contributed so generously to this book. They are all experts in their fields of interest, but have taken time to write on their subjects to make this work as comprehensive as possible.
