The stiffness‐controlled release of interleukin‐6 by cardiac fibroblasts is dependent on integrin α2β1

Abstract

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Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing

“…Elevated IL-6 levels in the culture medium are required for increased cell stiffness in Piezo1-transfected HAF, and for induction of PiCS in neighboring, non-Piezo1-transfected cells, i.e., IL-6 acts in an autocrine and in a paracrine manner. There is some evidence in the literature pointing to a connection between IL-6 and integrin signaling in cardiac fibroblasts, for example in response to differences in matrix stiffness [ 63 ]. It remains to be evaluated whether IL-6 signaling itself is sufficient, and integrin signaling is required for paracrine induction of PiCS.…”

Histamine is involved in the regulation of collagen content in cultured heart myofibroblasts via H2, H3 and H4 histamine receptors

“…Homeostasis of the extracellular matrix within the heart is dependent on cardiac fibroblasts, which account for 60-70% of cells in the human heart. These cells are responsible for the synthesis and breakdown of the extracellular matrix within the heart (1,2). They are also able to detect physical and biological stimuli; these stimuli may change the activity of the cardiac fibroblasts and their potential for collagen synthesis (2,3).…”

“…These cells are responsible for the synthesis and breakdown of the extracellular matrix within the heart (1,2). They are also able to detect physical and biological stimuli; these stimuli may change the activity of the cardiac fibroblasts and their potential for collagen synthesis (2,3). It has been found that heart fibroblasts secrete cytokines with autocrine or paracrine regulatory effects (2,3): Fibroblasts isolated from the heart of a patient with heart failure were found to release higher levels of cytokines under inflammatory conditions, and this effect was independent of hypoxia (3).…”

“…They are also able to detect physical and biological stimuli; these stimuli may change the activity of the cardiac fibroblasts and their potential for collagen synthesis (2,3). It has been found that heart fibroblasts secrete cytokines with autocrine or paracrine regulatory effects (2,3): Fibroblasts isolated from the heart of a patient with heart failure were found to release higher levels of cytokines under inflammatory conditions, and this effect was independent of hypoxia (3). The bioactive molecules secreted by the fibroblasts may exert regulatory effects on cardiomyocytes (2,4,5) or cardiac vessels (6,7).…”

“…Cardiac fibroblasts are involved in the regulation of the heart extracellular matrix under both physiological and pathological conditions (8). Collagen, the fibrotic protein of the extracellular matrix, not only provides mechanical support for cardiomyocytes (9), but is also responsible for the distribution of mechanical force within the heart (2) and can influence the electrophysiological processes within the myocardium (10). Collagen content determines compliance of the heart.…”