Catecholamine-Induced Senescence of Endothelial Cells and Bone Marrow Cells Promotes Cardiac Dysfunction in Mice.

Catecholamine-Induced Senescence of Endothelial Cells and Bone Marrow Cells Promotes Cardiac Dysfunction in Mice. Int Heart J. 2018 May 23;: Authors: Katsuumi G, Shimizu I, Yoshida Y, Hayashi Y, Ikegami R, Suda M, Wakasugi T, Nakao M, Minamino T Abstract Previous studies have suggested that cellular senescence plays a central role in the progression of pathologic changes in the failing heart. It is well known that the sympathetic nervous system is activated in patients with heart failure, and this change is associated with poor clinical outcomes. Sympathetic activation increases the levels of various catecholamines, such as epinephrine and norepinephrine, but the contribution of these catecholamines to cellular senescence associated with heart failure remains to be determined. We found that catecholamine infusion induced senescence of endothelial cells and bone marrow cells, and promoted cardiac dysfunction in mice. In C57BL/6NCr mice, the continuous infusion of isoproterenol-induced cardiac inflammation and cardiac dysfunction. Expression of p53, a master regulator of cellular senescence, was increased in the cardiac tissue and bone marrow cells of these mice. Suppression of cellular senescence by genetic deletion of p53 in endothelial cells or bone marrow cells led to improvement of isoproterenol-induced cardiac dysfunction. In vitro studies showed that adrenergic signaling increased the expression of p53 and adhesion molecules by ...
Source: International Heart Journal - Category: Cardiology Tags: Int Heart J Source Type: research