The permanent cellular constituents of the heart include cardiac fibroblasts, myocytes, endothelial cells and vascular smooth muscle cells. Previous studies have demonstrated that there are undulating changes in cardiac cell populations during embryonic development, through neonatal development and into the adult. Transient cell populations include lymphocytes, mast cells and macrophages, which can interact with these permanent cell types to affect cardiac function. It has also been observed that there are marked differences in the makeup of the cardiac cell populations depending on the species, which may be important when examining myocardial remodeling. Current dogma states that the fibroblast makes up the largest cell population of the heart; however, this appears to vary for different species, especially mice. Cardiac fibroblasts play a critical role in maintaining normal cardiac function, as well as in cardiac remodeling during pathological conditions such as myocardial infarct and hypertension. These cells have numerous functions, including synthesis and deposition of extracellular matrix, cell-cell communication with myocytes, cell-cell signaling with other fibroblasts, as well as with endothelial cells. These contacts affect the electrophysiological properties, secretion of growth factors and cytokines, as well as potentiating blood vessel formation. While a plethora of information is known about several of these processes, relatively little is understood about fibroblasts and their role in angiogenesis during development or cardiac remodeling. In this review we provide insight into the various properties of cardiac fibroblasts that helps illustrate their importance in maintaining proper cardiac function, as well as their critical role in the remodeling heart.

Cardiac fibroblasts, myocytes, endothelial cells, and vascular smooth muscle cells are the major cellular constituents of the heart. The aim of this study was to observe alterations in myocardial cell populations during early neonatal development in the adult animal and to observe any variations of the cardiac cell populations in different species, specifically, the rat and mouse. Whole hearts were isolated from either mice or rats during the neonatal and adult stages of development, and single cell suspensions were prepared via sequential collagenase digestion. Heterogeneous cell populations were immunolabeled for specific cell types and analyzed using fluorescence-activated cell sorting (FACS). In addition, the left ventricle, right ventricle, and septa were isolated, fixed, and sectioned for morphometric analyses. These same cardiac regions were also analyzed using FACS. We observed that the adult murine myocardium is composed of approximately 56% myocytes, 27% fibroblasts, 7% endothelial cells, and 10% vascular smooth muscle cells. Moreover, our morphometric and FACS data demonstrated similar percentages in the three regions examined. During murine neonatal cardiac development, we observed a marked increase in numbers of cardiac fibroblasts and a resultant decrease in percentages of myocytes in late neonatal development (day 15). Finally, FACS analyses of the rat heart during development displayed similar results in relation to increases in cardiac fibroblasts during development; however, cell populations in the rat differed markedly from those observed in the mouse. Taken together, these data enabled us to establish a homeostatic model for the myocardium that can be compared with genetic and cardiac disease models.

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Cardiac function is determined by the dynamic interaction of various cell types and the extracellular matrix that composes the heart. This interaction varies with the stage of development and the degree and duration of mechanical, chemical, and electrical signals between the various cell types and the ECM. Understanding how these complex signals interact at the molecular, cellular, and organ levels is critical to understanding the function of the heart under a variety of physiological and pathophysiological conditions. Quantitative approaches, both in vivo and in vitro, are essential to understand the dynamic interaction of mechanical, chemical, and electrical stimuli that govern cardiac function. The fibroblast can thus be a friend in normal function or a foe in pathophysiological conditions.

Cancer is one of the leading causes of death in the United States along with heart disease. The hallmark of cancer treatment has been conventional chemotherapy. Chemotherapeutic drugs are designed to target not only rapidly dividing cells, such as cancer cells, but also certain normal cells, such as intestinal epithelium. Over the past several years, a new generation of cancer treatment has come to the forefront, i.e, targeted cancer therapies. Like conventional chemotherapy, targeted cancer therapies use pharmacological agents that inhibit growth, increase cell death and restrict the spread of cancer. As the name suggests, targeted therapies interfere with specific proteins involved in tumorigenesis. Rather than using broad base cancer treatments, focusing on specific molecular changes which are unique to a particular cancer, targeted cancer therapies may be more therapeutically beneficial for many cancer types, including lung, colorectal, breast, lymphoma and leukemia. Moreover, recent advances have made it possible to analyze and tailor treatments to an individual patient's tumor. There are three main types of targeted cancer therapies; 1) monoclonal antibodies, 2) small molecule inhibitors and 3) immunotoxins. This review will discuss these three classes of targeted therapies in detail, as well as the biology behind targeted cancer therapies.