The Toxicity Mechanisms of Action of Aβ25–35 in Isolated Rat Cardiac Myocytes

Abstract

β-Amyloid (Aβ) is deposited in neurons and vascular cells of the brain and is characterized as a pathologic feature of Alzheimer’s disease (AD). Recently studies have reported that there is an association between cardiovascular risk factors and AD, however the mechanism of this association is still uncertain. In this study we observed Aβ had an effect on cardiovascular cells. We represent as a major discovery that Aβ25–35 had toxicity on isolated rat cardiac myocytes by impacting the cytoskeleton assembly and causing ER stress, ultimately contributing to the apoptosis of the myocytes. Importantly, the activation of ER stress and subsequent cellular dysfunction and apoptosis by Aβ25–35 was regulated by the MAPK pathway, which could be prevented by inhibition of p38 via pharmacological inhibitors. It was noteworthy that Aβ25–35 played a critical role in cardiac myocytes, suggesting that Alzheimer’s disease (AD) had a relation with the heart and understanding of these associations in future will help search for effective treatment strategies.

Keywords

• Alzheimer’s disease (AD)
• β-amyloid (Aβ)
• rat cardiac myocyte
• ER-stess
• p38