Dynamic Interactions between Myocytes, Fibroblasts, and Extracellular Matrix

Abstract

Cardiac function is determined by the coordinated and dynamic interaction of several cell types together with components of the extracellular matrix (ECM). This interaction is regulated by mechanical, chemical, and electrical signals between the cellular and noncellular components of the heart. Recent studies using fluorescence-activated cell sorting indicate that the number of myocytes remains relatively constant during development and disease, whereas the number of fibroblasts and other cell types can change dramatically. Cardiac fibroblasts appear to have different origins at different stages of development and fluctuate in response to a variety of physiological signals. Fibroblasts form a network of cells that are connected to each other via specific cadherins and connexins, to the ECM via integrins, and to myocytes by a variety of receptors, including connexins. Examples of the integration of signals include the role of angiotensin II (Ang II), which stimulates mechanical contraction of fibroblasts, as well as cytokine signaling. Cytokine signaling alters connexin and K(+) channel activation, which in turn is regulated by Ang II, essentially forming a feedback loop. Quantitative changes in mechanical, chemical, and electrical signals that can alter the overall cardiac form and function will be discussed here.

Distinct biological events generated by ECM proteolysis by two homologous collagenases

“…S2E and Datasets S1 and S2). Induction was observed in protocadherins (Pcdhga3, Pcdhga5, and Pcdhga8), which are involved in cell adhesion and have been shown to interact with a wide range of binding partners, resulting in cytoskeleton changes (31,32) as well as transcription factor 3 (Tcf3), which is involved in cell migration and wound healing. The elevated expression of the Pcdhga3 and Pcdhga5 genes can be related to direct and indirect cellular adhesion properties corroborated by a large number of other interacting proteins, including phosphatases, kinases, and adhesion molecules.…”

Neonatal rat cardiac fibroblasts express three types of voltage-gated K+ channels: regulation of a transient outward current by protein kinase C

“…For example, coculture of fibroblasts with myocytes dramatically enhances the expression of cytokines such as IL-6, IL-10, and tumor necrosis factor-␣, compared with cells cultured separately (2,15). These factors in turn alter the structural and contractile properties of the myocytes (2,15). Establishment of electrical contact between adjacent fibroblasts and myocytes may be of critical importance in the release of these cytokines and growth factors.…”

“…Although cardiac myocytes make up the bulk of the myocardial volume, the cardiac fibroblast is the most numerous cell type found in the heart and functions in the deposition of the extracellular matrix (2, 3). In addition, fibroblasts can serve as "sentinel cells" that coordinate the myocardial response to chemical and mechanical stimulation through the release of cytokines and growth factors (2,3,15). Release of these signals during myocardial injury may regulate the extent of cardiac hypertrophy and fibrosis during the healing process (5, 15).…”

Histomorphometric Evaluation of the Small Coronary Arteries in Rats Exposed to Industrial Noise

“…It remains to understand the fibrotic proliferation mechanism behind the IN. A strong possibility, taking into consideration the dynamic interactions between fibroblasts and the extracellular matrix [11], could be the occurrence of an abnormal biological fibroblastic response induced by IN through a mecanotransduction process [12]. In addition, we could speculate that IN can induce fibrosis through the loss of regulation between profibrotic and antifibrotic molecules, carried out by mechanical and neurohumoral factors [13].…”