Contribution of α‐smooth muscle actin and extracellular matrix to the in vitro reorganization of cardiomyocyte contractile system

Abstract

Cardiomyocytes in culture undergo reversible rearrangement of their contractile apparatus with the conversion of typical myofibrils into the structures of non-muscle type and the loss of contractility. Along with these transformations, the cardiomyocytes gain the capacity to synthesize extracellular matrix. Here we show that during cultivation of rat neonatal cardiomyocytes, the inherent α-cardiac actin isoform is transiently replaced by α-smooth-muscle actin, whose expression is accompanied by transformation of myofibrils into stress-fiber-like structures. The following down-regulation of α-smooth muscle actin parallels restoration of myofibrillar system and correlates with the accumulation of extracellular collagen and laminin, initially missing from the cardiomyocytes culture.

Extracellular Matrix in Regulation of Contractile System in Cardiomyocytes

“…Interestingly, the phenomenon of rearrangement is accompanied by transient replacement of the inherent α-cardiac actin with α-smooth-muscle isoform [2,8,9,10,11]. Since smooth muscle α-actin is characteristic of embryonic CMs, many researchers consider it to be a marker of dedifferentiation of these cells [93,94].…”

“…Our previous results show that the appearance of smooth muscle α-actin precedes the transformation of myofibrils into structures of non-muscle type and corresponds to the inhibition of contractile activity. Interestingly, myofibrils that are still present in the cells are intensely stained with antibodies against smooth muscle actin along with non-striated structures [11]. To date, quite a lot of data has accumulated to indicate that different actin isoforms, despite conservative sequences, cannot replace each other without affecting thefunction [95,96,97,98,99,100,101].…”

“…These changes are accompanied by a decrease in smooth muscle actin isoform, which leaves the area occupied by the newly formed myofibrils. Interestingly, at the initial stages of myofibrillar apparatus recovery, a small amount of smooth muscle actin is detected in some fragments of nascent myofibrils, suggesting that myofibrils are formed by gradual replacement of smooth muscle isoform with cardiac actin [11].…”

“…Similar processes are observed in cell adaptation to the culture system, where CMs undergo the reversible rearrangement of their contractile apparatus with the conversion of typical myofibrils into structures of non-muscle type and the loss of contractility. This phenomenon is accompanied by the transient replacement of the inherent α-cardiac actin with α-smooth-muscle isoform [2,8,9,10,11]. The following down-regulation of α-smooth muscle actin goes along with the expression of cardiac isoform and myofibrillar system recovery [11].…”

“…This phenomenon is accompanied by the transient replacement of the inherent α-cardiac actin with α-smooth-muscle isoform [2,8,9,10,11]. The following down-regulation of α-smooth muscle actin goes along with the expression of cardiac isoform and myofibrillar system recovery [11]. During these rearrangements, actin isoforms are shown to have different distribution patterns within the cells and appear to play distinct and non-redundant roles suggesting their spatiotemporal regulation.…”