The Emerging Role of TXNIP in Ischemic and Cardiovascular Diseases; A Novel Marker and Therapeutic Target

Abstract

Thioredoxin interacting protein (TXNIP) is a metabolism- oxidative- and inflammation-related marker induced in cardiovascular diseases and is believed to represent a possible link between metabolism and cellular redox status. TXNIP is a potential biomarker in cardiovascular and ischemic diseases but also a novel identified target for preventive and curative medicine. The goal of this review is to focus on the novelties concerning TXNIP. After an overview in TXNIP involvement in oxidative stress, inflammation and metabolism, the remainder of this review presents the clues used to define TXNIP as a new marker at the genetic, blood, or ischemic site level in the context of cardiovascular and ischemic diseases.

The Role of Mitochondria-Derived Peptides in Cardiovascular Diseases and Their Potential as Therapeutic Targets

“…In experiments on human aortic endothelial cells, HN treatment protects from OS via downregulation of NOX2 (Superoxide-Generating NADPH Oxidase Heavy Chain Subunit) and TxNIP (Thioredoxin Interacting Protein) gene expression and leads to a reduction in ROS and protein carbonyl [65]. NOX2 is the main player in cardiac oxidative damage [78], while TxNIP and protein carbonyl are markers of metabolic and oxidative stress [79,80]. Similarly, protective properties against oxidative stress were shown for HN analogue HNG on SH-SY5Y neuroblastoma cells, where HNG acted via the PI3K/AKT (phosphatidylinositol 3-kinase/protein kinase B) pathway [81], a crucial signalling pathway involved in the regulation of apoptosis, cell differentiation and proliferation [82].…”

The Emerging Role of Metabolism in Brain-Heart Axis: New Challenge for the Therapy and Prevention of Alzheimer Disease. May Thioredoxin Interacting Protein (TXNIP) Play a Role?

“…Hyperglycemia in vivo and high glucose conditions (HG) in vitro promote TXNIP expression [ 21 ], TXNIP plays a pathological role in both type 1 and Type 2 diabetes [ 20 ] and is also involved in the pathophysiology of diabetic complications, including diabetic retinopathy [ 22 ]. TXNIP possesses an α-arrestin domain, which promotes the intracellular trafficking of plasma membrane associated proteins and drives the transport of proteins in different subcellular localizations [ 23 ]. Moreover, the α-arrestin domain is responsible for the Trx-independent functions of TXNIP.…”

“…Moreover, the α-arrestin domain is responsible for the Trx-independent functions of TXNIP. TXNIP is a shuttle protein that can translocate in different subcellular compartments [ 23 ]. In the majority of the cells in normal conditions, TXNIP shows a nuclear localization.…”

“…In the majority of the cells in normal conditions, TXNIP shows a nuclear localization. However, following different stimulations, TXNIP can translocate in other subcellular compartments, where it exerts specific functions [ 23 ]. TXNIP may translocate into the mitochondria, where it blocks the ROS scavenger activity of Trx2, leading to oxidative stress [ 23 ].…”

“…However, following different stimulations, TXNIP can translocate in other subcellular compartments, where it exerts specific functions [ 23 ]. TXNIP may translocate into the mitochondria, where it blocks the ROS scavenger activity of Trx2, leading to oxidative stress [ 23 ]. TXNIP also promotes the nuclear translocation of the transcription factor NF-kB, leading to the expression of pro-inflammatory genes [ 21 ].…”