Ca Signaling in Cardiovascular Fibroblasts.

Fibrogenesis is a physiological process required for wound healing and tissue repair. It is induced by activation of quiescent fibroblasts, which first proliferate and then change their phenotype into migratory, contractile myofibroblasts. Myofibroblasts secrete extracellular matrix proteins, such as collagen, to form a scar. Once the healing process is terminated, most myofibroblasts undergo apoptosis. However, in some tissues, such as the heart, myofibroblasts remain active and sensitive to neurohumoral factors and inflammatory mediators, which lead eventually to excessive organ fibrosis. Many cellular processes involved in fibroblast activation, including cell proliferation, protein secretion and cell contraction, are highly regulated by intracellular Ca signals. This review summarizes current research on Ca signaling pathways underlying fibroblast activation. We present receptor- and ion channel-mediated Ca signaling pathways, discuss how localized Ca signals of the cell nucleus may be involved in fibroblast activation and present Ca-sensitive transcription pathways relevant for fibroblast biology. When investigated, we highlight how the function of Ca-handling proteins changes during cardiac and pulmonary fibrosis. Many aspects of Ca signaling remain unexplored in different types of cardiovascular fibroblasts in relation to pathologies, and a better understanding of Ca signaling in fibroblasts will help to design targeted therapies against fibrosis.