Beta-Amyloid Instigates Dysfunction of Mitochondria in Cardiac Cells

Abstract

Alzheimer’s disease (AD) includes the formation of extracellular deposits comprising aggregated β-amyloid (Aβ) 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 Aβ in cardiac cells, remain unknown. Here, we investigated the role of mitochondria in mediating the effects of Aβ1-40 and Aβ1-42 in cultured cardiomyocytes and primary coronary endothelial cells. Our results demonstrated that Aβ1-40 and Aβ1-42 are differently accumulated in cardiomyocytes and coronary endothelial cells. Aβ1-42 had more adverse effects than Aβ1-40 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 Aβ1-42. Mitochondrial dysfunction induced by Aβ was associated with apoptosis of the cells. The effects of Aβ1-42 on mitochondria and cell death were more evident in coronary endothelial cells. In addition, Aβ1-40 and Aβ1-42 significantly increased Ca2+ -induced swelling in mitochondria isolated from the intact rat hearts. In conclusion, this study demonstrates the toxic effects of Aβ on cell survival and mitochondria function in cardiac cells.

Diminished α7 nicotinic acetylcholine receptor (α7nAChR) rescues amyloid-β induced atrial remodeling by oxi-CaMKII/MAPK/AP-1 axis-mediated mitochondrial oxidative stress

“…The pulmonary vein contains abundant amyloid peptides and directly influences atrial remodeling as a major substrate of AF [ 35 ]. Moreover, cardiac dysfunction of AD model mice and cytotoxicity of Aβ to cardiomyocytes have been reported [ 24 , 36 , 37 ]. Our study and others have reported that mitochondrial oxidative stress plays a pivotal role in the pathogenesis of both AD and AF [ 20 , 38 ], which could be attributed to Ca 2+ overload, ROS generation and energy deprivation [ 39 ].…”

“…Re-dissolved the lyophilized amyloid-β in DMSO and diluted it to 1 mM in deionized water. After incubating at 4 °C for 48 h to form oligomers, amyloid-β was diluted in culture media to the final concentration of 50 μM [ 24 ]. Then, HL-1 cells were administrated by Aβ after serum starvation, and cells in control group were treated with same volume of DMSO at 0.1% (v/v) in deionized water.…”

Hypoxia-inducible Factor-1α protects against Intervertebral Disc Degeneration through Antagonizing Mitochondrial Oxidative Stress.

“…Mitochondria, as the center of cellular energy metabolism, is involved in a variety of signaling pathways and regulates cellular function and survival [36]. After mitochondria is exposed to adverse stimulation, it will occur multiple harmful changes such as increased oxidative stress, swelling and deformation, and decreased membrane potential [37,38]. These changes can lead to in ammasome activation, cell senescence and death, which plays a crucial role in some degenerative diseases [39].…”

Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in obesity

“…In these studies, an increase in ABAD was associated with reduced respiratory responses in both sub-sarcolemmal and inter-myofibrillar mitochondria 60 and increased injury in response to ischemia/reperfusion 61 . Furthermore, exposure of isolated rat heart mitochondria or immortalised H9C2 cardiomyoblasts to Aβ 42 causes mitochondrial dysfunction, not only affecting energetics but also resulting in elevated ROS production, a loss of mitochondrial membrane potential, mitochondrial swelling, and impaired capacity to retain calcium 62 . In contrast, Aβ 40 had less pronounced effects on these parameters of mitochondrial function 62 .…”

“…Furthermore, exposure of isolated rat heart mitochondria or immortalised H9C2 cardiomyoblasts to Aβ 42 causes mitochondrial dysfunction, not only affecting energetics but also resulting in elevated ROS production, a loss of mitochondrial membrane potential, mitochondrial swelling, and impaired capacity to retain calcium 62 . In contrast, Aβ 40 had less pronounced effects on these parameters of mitochondrial function 62 . Together, these findings support our conclusion that the effects of Aβ 42 on the heart are in part due to the internalisation of Aβ 42 , but not Aβ 40 , by cardiomyocytes.…”