Cardiac Fibroblast Physiology and Pathology

Abstract

Cardiac function is mediated by interactions between the cellular constituents of the heart, as well as the extracellular matrix. The major cell types of the heart include cardiac fibroblasts, myocytes, endothelial cells, and vascular smooth muscle cells. In addition, there are also resident stem cells and transient cell types, such as immune cells. Interactions in the heart include chemical, mechanical, and electrical signals, which vary depending on the developmental stage, disease state, and specific cell type. Understanding how these different signals interact at the molecular, cellular, and organ levels is important for better understanding cardiac function under a variety of physiological and pathological conditions. Cardiac fibroblasts play key roles in maintaining normal cardiac form and function, as well as in the cardiac remodeling process during pathological conditions, such as myocardial infarction and hypertension. Regardless of normal or pathological status of the heart, fibroblasts have multiple functions, such as synthesis and deposition of extracellular matrix and cell-cell communication with other cardiac cells, including myocytes and endothelial cells. Interactions with other cell types can affect multiple cell signaling pathways (e.g., ERK, JNK, and p38), the expression and secretion of numerous growth factors and cytokines, microRNA exchange, gene and protein expression, and angiogenesis. In this review, we provide insight into the cardiac fibroblast under normal and pathological conditions to illustrate their importance in maintaining proper cardiac function.

Cardiac fibroblast‐specific p38α MAP kinase promotes cardiac hypertrophy via a putative paracrine interleukin‐6 signaling mechanism

“…Cardiac fibroblasts are one of the most-prevalent, nonmyocyte cell populations in the heart, accounting for between one-fifth and two-thirds of cardiac cells, depending on the species (16)(17)(18). Although traditionally viewed solely in relation to extracellular matrix remodeling, cardiac fibroblasts are now acknowledged as being important nodal regulators of multiple aspects of cardiac function under both physiologic and pathophysiologic conditions (19)(20)(21). Importantly, recent studies have revealed that fibroblasts have a critical role in inducing cardiomyocyte hypertrophy in vivo through paracrine secretion of growth factors and other signaling molecules (22,23).…”

Extracellular matrix-mediated cellular communication in the heart

“…Upon cardiac injury, CF respond to these signals by transforming to smooth muscle actin-expressing “myofibroblasts,” leading to changes in proliferation and migration as well as secretion of ECM proteins to promote wound healing (Figure 2). Myofibroblasts secrete large amounts of ECM proteins including collagens, fibronectin, periostin, MMPs and their inhibitors, TIMPs [110, 111]. Specifically, CF have been shown to secrete MMP-1,-2,-3,-9,-13,-14 and TIMP-1,-2,-3 and -4 after injury or pathologic stimulation [14, 112, 113].…”

Heart Remodelation: Role of MMPs

“…Fibroblasts also produce a number of cytokines, peptides, and enzymes including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) that directly affect the ECM turnover and homeostasis. In turn, as a feedback, function of fibroblasts can also be regulated by MMPs and TIMPs [12,13].…”