Beta-Amyloid Instigates Dysfunction of Mitochondria in Cardiac Cells.

ABSTRACT

Alzheimer's disease (AD) includes the formation of extracellular deposits comprising aggregated ß-amyloid (Aß) fibers associated with oxidative stress, inflammation, mitochondrial abnormalities, and neuronal loss. There is an associative link between AD and cardiac diseases; however, the mechanisms underlying the potential role of AD, particularly Aß in cardiac cells, remain unknown. Here, we investigated the role of mitochondria in mediating the effects of Aß1-40 and Aß1-42 in cultured cardiomyocytes and primary coronary endothelial cells. Our results demonstrated that Aß1-40 and Aß1-42 are differently accumulated in cardiomyocytes and coronary endothelial cells. Aß1-42 had more adverse effects than Aß1-40 on cell viability and mitochondrial function in both types of cells. Mitochondrial and cellular ROS were significantly increased, whereas mitochondrial membrane potential and calcium retention capacity decreased in both types of cells in response to Aß1-42. Mitochondrial dysfunction induced by Aß was associated with apoptosis of the cells. The effects of Aß1-42 on mitochondria and cell death were more evident in coronary endothelial cells. In addition, Aß1-40 and Aß1-42 significantly increased Ca2+ -induced swelling in mitochondria isolated from the intact rat hearts. In conclusion, this study demonstrates the toxic effects of Aß on cell survival and mitochondria function in cardiac cells.