Aberrant Mitochondrial Dynamics: An Emerging Pathogenic Driver of Abdominal Aortic Aneurysm

Abstract

Abdominal aortic aneurysm (AAA) is defined as a progressive segmental dilation of the abdominal aorta and is associated with high mortality. The characterized features of AAA indicate several underlying mechanisms of AAA formation and progression, including reactive oxygen species production, inflammation, and atherosclerosis. Mitochondrial functions are critical for determining cell fate, and mitochondrial dynamics, especially selective mitochondrial autophagy, which is termed as mitophagy, has emerged as an important player in the pathogenesis of several cardiovascular diseases. The PARKIN/PARIS/PGC1α pathway is associated with AAA formation and has been proposed to play a role in mitochondrial dynamics mediated by the PINK/PARKIN pathway in the pathogenesis underlying AAA. This review is aimed at deepening our understanding of AAA formation and progression, which is vital for the development of potential medical therapies for AAA.

Differential expression analyses on aortic tissue reveal novel genes and pathways associated with abdominal aortic aneurysm onset and progression

“…While the detection of the ATP synthesis regulatory pathway is novel, it is in line with previous work associating mitochondrial disfunction and AAA [23,24]. On the other hand, previous differential expression studies in microarrays between AAA and control aortic tissue have consistently found associations of immune system pathways with AAA.…”

“…Our results indicate that 88 % (22 / 25) of the DEGs coding for the subunits of the complexes that form the electron transport chain are expressed to a lower extent in AAA, suggesting a lower synthesis of ATP in AAA tissue. Mitochondrial dysfunction has previously been studied in the development of AAA [23,24] and other cardiovascular diseases [25] due to its key role in some of the cellular alterations characteristic of cardiovascular diseases, including excessive production of reactive oxygen species, energy depletion, endoplasmic reticulum stress, and activation of apoptosis. However, this is the first time that these metabolic pathways have been characterized in a DEGs study of AAA, confirming the role of mitochondrial dysfunction on AAA.…”

Mitochondrial Dysfunction and Increased DNA Damage in Vascular Smooth Muscle Cells of Abdominal Aortic Aneurysm (AAA-SMC)

“…Moreover, mtDNA can be released from defective mitochondria and accumulate outside of mitochondria if not properly removed. Thus, the high mtDNA copy number in combination with an increased fission to fusion rate may indicate defects in mitophagy in AAA-SMC, as it has been suggested by others [42]. Clear evidence of defective mitophagy in VSMC and its underlying causes in the course of AAA disease is still pending.…”

The hydrogen sulfide donor sodium thiosulfate limits inflammation but aggravate smooth muscle cells apoptosis and aneurysm progression in a mouse model of abdominal aortic aneurysm

“…STS-induced cell cycle arrest probably tips the balance between pro and antiapoptotic signals toward apoptosis even though STS may induce cytoprotective mechanism. Indeed, we observed that STS promotes mitochondrial biogenesis, which is associated with improved function, stress resistance and cell survival 35,54,55 . STS stimulates the expression of the master regulator of mitochondrial biogenesis PGC-1α and downstream transcription factor NRF1.…”