Abstract| Volume 23, ISSUE 10, SUPPLEMENT , S40, October 2017

Continuous Activation of Adrenergic Signaling Promotes Cardiac Inflammation and Remodeling via Developing Cellular Senescence in Endothelium and Bone Marrow

      Catecholamine, such as norepinephrine, plays a central role in the activation of adrenergic signaling. There is evidence that catecholamine-release is increased during heart failure, however, contribution to the pathology of heart failure remains to be defined. Here we show that continuous catecholamine-infusion induces cellular senescence in endothelial cells and bone marrow cells and promote pathologies by inducing cardiac inflammation in a murine heart failure model. Continuous isoproterenol infusion into C57B6/NCr mice induced cardiac dysfunction and promoted cardiac inflammation. In these mice, we found that expression of p53, known as a key molecule for inducing cellular senescence, is increased in cardiac tissue and bone marrow cells. Suppression of cellular senescence with genetic deletion of p53 in endothelial cells or bone marrow cells suppressed isoproterenol-induced cardiac inflammation and remodeling. In vitro studies showed that constitutive activation of adrenergic signaling would increase the expression of adhesion molecules in endothelial cells and macrophages via promoting p53 signaling. Our results indicate that catecholamine-induced cellular senescence in endothelium and bone marrow plays a crucial role in the progression of heart failure by promoting inflammatory response in cardiac tissue. Suppression of adrenergic signaling-p53-cellular senescence pathway is crucial for the inhibition of pathologies in heart failure.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Cardiac Failure
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect