1. Introduction

Cardiovascular diseases remain a major cause of death worldwide and are increasing due to the ageing population and poor eating habits. The pathological changes are originally characterized by metabolic disorders and endothelial dysfunction. Oxidative stress plays an important role and induces vascular-related gene expression, promoting local inflammatory response and cell life and death dysregulation. When oxidative stress occurs, vascular walls produce excessive reactive oxygen species (ROS), which causes damage to the structure and function of endothelial cells. That enhances the inflammatory response of the vascular wall and impairs vascular function or revascularization. ROS are produced continuously during cell metabolism and are used as mediators in many biological processes. Specifically, ROS reversibly activate signaling pathways that trigger adaptation systems in the cell. Previous works have associated excessive ROS with age-related pathologies [1,2,3,4,5,6,7]. However, recent reviews still report that excessive ROS can lead to diseases and pathological conditions [8,9,10,11]. Thioredoxin interacting protein (TXNIP) is a metabolism- oxidative- and inflammation-related marker induced in cardiovascular pathologies and could represent an emergent link between physiopathology and cardiovascular events. More precisely, TXNIP has been widely described as a pro-oxidant compound [12,13], but it is also a regulator of metabolism [14,15,16,17], a modulator of the inflammatory [18,19] or angiogenic response [20,21], and an antiproliferative and pro-apoptotic agent [22,23]. Clinically, genetic association studies have shown that polymorphisms affecting TXNIP expression are linked to hypertension and arterial stiffness and increase the risk of coronary heart disease [24,25,26]. Epigenetic modifications of TXNIP are also associated with risks of cardiovascular diseases [27,28]. Additionally, blood or mononuclear blood cells’ mRNA TXNIP levels have been related to coronary and heart diseases [29,30,31].

2. TXNIP is a Multifunctional Protein

3. TXNIP is a Novel Marker in Cardiovascular Diseases

TXNIP is a genetic, blood, peripheral blood cells, and tissue ischemia marker associated with cardiovascular diseases, as summarized in Figure 2 and in Table 2, thus making TXNIP an interesting target for prognostic and treatment.

Figure 2. TXNIP overexpression is associated with cardiovascular outcomes and diseases. Tissue, blood levels of TXNIP, and the genetic regulation of TXNIP make it a potential marker associated with cardiovascular risk factors or cardiovascular event or diseases. Created with BioRender.com.

Table 2. TXNIP as a marker of cardiovascular risk and disease.

	Location	Parameter or Disease	References
Genetic Marker	TXNIP rs7211 variant	Arterial stiffness, obesity	[24,151]
	TXNIP rs7211- rs7212 variants	Glucose, blood pressure, coronary atherosclerosis	[24,26]
	Various epigenetic changes	T2D	[188,189]
	DNA methylation cg19693031	Blood pressure, T2D, coronary artery disease	[26,27,28,190,191,192,193,194,195,196,197]
		Triglycerides and/or HbA1C levels	[27,190,191,192,193,198]
Blood Marker	Plasma or serum levels of TXNIP	Carotid Intima Media Thickness	[30]
		Stroke or heart attack	[55,199]
		Diabetes associated macrovascular endothelial dysfunction	[17]
		Diabetes associated vascular complications	[19]
mRNA Marker	TXNIP in peripheral blood cells	At-risk Takayasu arteritis, atherosclerosis, coronary artery disease, leukostasis	[80,94,110,200,201,202,203]
		Unstable angina pectoris, acute myocardial infarction	[29,204]
		Diabetes associated macrovascular endothelial dysfunction	[17]
		Diabetes associated vascular complications	[19,205]
	TXNIP in cardiac tissue	Heart attack	[55]
	TXNIP in aortic tissue	At-risk Takayasu arteritis, atherosclerosis, arterial aging	[51,200,202,206]
		Diabetes associated macrovascular endothelial dysfunction	[17]
		Diabetes associated vascular complications	[19]
Tissue Marker	TXNIP in bonne marrow	Mobilization of cells	[202]
	TXNIP in Myocardiac ischemia	I/R damage (infarct size or ventricular remodeling or heart failure or atrial fibrillation)	[207,208]
		I/R damage in diabetic hearts or survival	[64,100,109,209,210,211,212,213,214]
	TXNIP in Hind limb ischemia	Reperfusion of ischemic limb, tissue-recovery, capillary density in diabetic mouse	[173,215,216]
		Reperfusion of ischemic limb, tissue-recovery, capillary density in mouse with fat diet	[217,218]
	TXNIP in cerebral ischemia	Ischemic stroke	[58,60,61,102,103,108,127,219,220,221,222,223,224,225,226,227]
		Subarachnoid haemorrhage	[62,228,229,230]
		Neonatal hypoxic-ischemia	[124,125,231]
		Vascular dementia	[232]

 

This entry is adapted from the peer-reviewed paper 10.3390/ijms22041693