Changes in the extracellular matrix of cardiomyocytes by electrical microcurrent application. A possible novel approach for the treatment of heart failure

The application of cardiac assist devices has revealed that end-stage heart failure can be reversed. In investigations on the myocardial level, the normalization of the extracellular matrix function was found most important. Electrical microcurrent can modulate the collagen composition (collagen I and III) of the extracellular matrix. We investigated the effect of electrical microcurrent on cardiomyocytes under culture conditions. The influence of low (50µA) and high (100µA) microcurrent on cultured cardiomyocytes from adult rats was compared to cultured cardiomyocytes without application of microcurrent (control). Changes in the cell proliferation; collagen I, III; in MMP 2, 3, 8, 9, 13, 14, 16; TIMP 1, 2; IL-1, 6; TNF-α; TGF-β; GM-CSF; connexin 40, 43, 45 were measured. After 90h of cultivation, compared to the control cultured cardiomyocytes proliferation increased by 70% under low microcurrent application. Collagen I synthesis decreased by 35% (low microcurrent) and collagen III increased by 100% (high microcurrent). The MMPs (3, 8, 9, 16) expression showed a significant decrease at high microcurrent application. The TIMPs remained unaffected. IL-6 was suppressed by high microcurrent. TNF-α, IL-1 and GM-CSF were not detected at all. High microcurrent leads to a reduced IL-6 and TGF-β expression. As sign for the viability and functionality of the myocytes the connexin 40, 43, and 45 showed the most pronounced increase when stimulated by low microcurrent. Microcurrent application on cardiomyocytes can influence the components of the extracellular matrix. So it may be conceivable to influence the extracellular matrix by electrical microcurrent to normalize their function.