NADPH Oxidases in Aortic Aneurysms

Abstract

Abdominal aortic aneurysms (AAAs) are a progressive dilation of the infrarenal aorta and are characterized by inflammatory cell infiltration, smooth muscle cell migration and proliferation, and degradation of the extracellular matrix. Oxidative stress and the production of reactive oxygen species (ROS) have been shown to play roles in inflammatory cell infiltration, and smooth muscle cell migration and apoptosis in AAAs. In this review, we discuss the principles of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase/NOX) signaling and activation. We also discuss the effects of some of the major mediators of NOX signaling in AAAs. Separately, we also discuss the influence of genetic or pharmacologic inhibitors of NADPH oxidases on experimental pre-clinical AAAs. Experimental evidence suggests that NADPH oxidases may be a promising future therapeutic target for developing pharmacologic treatment strategies for halting AAA progression or rupture prevention in the management of clinical AAAs.

ER stress mediates Angiotensin II-augmented innate immunity memory and facilitates distinct susceptibilities of thoracic from abdominal aorta to aneurysm development

“…Previous reports showed that ROS plays significant roles in promoting the pathogenesis of aortic aneurysms ( 60 – 62 ) via enhancing inflammatory cell infiltration, smooth muscle cell migration, and apoptosis in AAAs ( 63 ). We also reported that ROS in the ER, mitochondria, and other organelles ( 64 ) are interconnected in sensing metabolic stress ( 65 ).…”

The occurrence and development of abdominal aortic aneurysm may be related to the energy metabolism disorder and local inflammation

“…This results in a perpetuating cycle of inflammation and oxidative stress, amplifying the vascular damage observed in AAA [ 21 ]. The upregulation of NADPH oxidases, responsible for ROS generation, signifies a pivotal event in this oxidative milieu, further underscoring the complexity of the molecular landscape [ 22 ].…”

Towards Precritical Medical Therapy of the Abdominal Aortic Aneurysm

“…Pathological oxidative stress (OS) is defined as an imbalance between reactive oxygen species (ROS) and antioxidants, in favour of the former, leading to a disruption of redox signalling with consequence of oxidative damage to lipids, proteins and DNA. Increased activity of NAD(P)H oxidase, inflammation, over-expression of inducible nitric oxide synthase (iNOS), iron release from hemoglobin and endothelial dysfunction resulting in uncoupled endothelial nitric oxide synthase (eNOS) are recognized to be important sources of ROS production in AAA [ 10 , 11 ]. Therefore, reducing OS using antioxidants and especially dietary polyphenols could represent a potential strategy for limiting AAA development.…”