Beta-Amyloid Instigates Dysfunction of Mitochondria in Cardiac Cells.

Sehwan Jang,Rebecca M Parodi-Rullán,Sabzali Javadov,Silvia Fossati,Xavier R Chapa-Dubocq

doi:10.3390/cells11030373

Sehwan Jang, Rebecca M Parodi-Rullán + Show 3 more

Open Access

https://doi.org/10.3390/cells11030373

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Journal: Cells	Publication Date: Jan 22, 2022
Citations: 15	License type: CC BY 4.0

Affiliation: Temple University, University of Puerto Rico System

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.

Highlights

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is expected to affect 13 million individuals, mostly older adults, in the U.S by 2050 [1]
Our results demonstrated that Aβ1-40 and Aβ1-42 differentially affected cell viability and mitochondrial function; Aβ, mostly Aβ1-42 was found aggregated and instigated mitochondrial dysfunction associated with increased mitochondrial ROS and swelling, and reduced mitochondrial membrane potential (∆Ψm), and calcium retention capacity (CRC)
Our study and others have reported that mitochondrial dysfunction and mitochondria-mediated apoptosis play a crucial role in the pathogenesis of both AD and heart failure [19,35]

Summary

Introduction

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is expected to affect 13 million individuals, mostly older adults, in the U.S by 2050 [1]. The main pathological characteristics of AD are the formation of extracellular deposits comprising aggregated β-amyloid (Aβ) fibers and intracellular neurofibrillary tangles formed by hyperphosphorylated tau protein. These alterations are associated with the loss of synapses, mitochondrial structural and functional abnormalities, oxidative stress, inflammation, and neuronal loss. Oxidative stress can induce further production of Aβ and tau protein, another critical component involved in the pathogenesis of AD [4] These studies suggest a feedback loop embedded in the crosstalk between oxidative stress and Aβ aggregation that stimulates the development and progression of AD. A causal role of cardiac dysfunction in AD progression can be explained, at least partially, by oxidative stress induced by decreased cerebral blood flow (hypoperfusion), it remains unclear whether AD per se can increase the risk for developing cardiac abnormalities

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