The TRPA1 Channel in the Cardiovascular System: Promising Features and Challenges

Abstract

The transient receptor potential ankyrin 1 (TRPA1) channel is a calcium-permeable nonselective cation channel in the plasma membrane that belongs to the transient receptor potential (TRP) channel superfamily. Recent studies have suggested that the TRPA1 channel plays an essential role in the development and progression of several cardiovascular conditions, such as atherosclerosis, heart failure, myocardial ischemia–reperfusion injury, myocardial fibrosis, arrhythmia, vasodilation, and hypertension. Activation of the TRPA1 channel has a protective effect against the development of atherosclerosis. Furthermore, TRPA1 channel activation elicits peripheral vasodilation and induces a biphasic blood pressure response. However, loss of channel expression or blockade of its activation suppressed heart failure, myocardial ischemia–reperfusion injury, myocardial fibrosis, and arrhythmia. In this paper, we review recent research progress on the TRPA1 channel and discuss its potential role in the cardiovascular system.

Proximal C-Terminus Serves as a Signaling Hub for TRPA1 Channel Regulation via Its Interacting Molecules and Supramolecular Complexes

“…The Transient Receptor Potential (TRP) Ankyrin subtype 1 (TRPA1), originally called ANKTM1 (Story et al, 2003), is a cation channel expressed in a subset of dorsal root, trigeminal and visceral primary sensory neurons (Bautista et al, 2006;Kwan et al, 2006), but also in non-neuronal cells such as keratinocytes (Kwan et al, 2006), fibroblasts (Jaquemar et al, 1999), odontoblasts (El Karim et al, 2011), astroglia (Shigetomi et al, 2011), Schwann cells (De Logu et al, 2017), endothelial cells, and arterial vessels (Kwan et al, 2009). There, TRPA1 acts as a polymodal sensor of cell threats, being activated by a wide range of physical and chemical stimuli of extracellular or intracellular origin (for comprehensive reviews see (Zygmunt and Hogestatt, 2014;Chen and Hackos, 2015;Viana, 2016;Gouin et al, 2017;Koivisto et al, 2018;Wang et al, 2019) and references therein). Accumulating evidence links the physiological functions of TRPA1 to inflammation, temperature perception, mechanosensation, insulin secretion, itching, respiratory functions, regulation of the cardiovascular system, but also the homeostatic balance between the immune and nociceptive systems, as recently nicely reviewed by Talavera et al (2019).…”

Involvement of Neural Transient Receptor Potential Channels in Peripheral Inflammation

“…Additionally, TRPA1 channels can be found on non-neuronal cell types. TRPA1 was first cloned in fibroblasts (67) and has since been found to be expressed on T-cells, macrophages, endothelial cells, epithelial cells, and smooth muscle cells (50,(68)(69)(70)(71). Along with its role as a thermo-and mechanosensory, TRPA1 is activated by a wide variety of chemical stimuli such as cinnamaldehyde, allyl isothiocyanate (AITC), allicin, hydrogen peroxide, oxygen (O 2 ), n i t r o x y l ( H N O ) , m e t h y l g l y o x a l , a n d e n d o t o x i n (lipopolysaccharide; LPS) ( Figure 2) (4, 72-75).…”

Capsaicin-Sensitive Sensory Nerves and the TRPV1 Ion Channel in Cardiac Physiology and Pathologies

“…The transient receptor potential ankyrin 1 (TRPA1) is a very similar ion channel that is strongly co-localized with TRPV1 on sensory nerves, vascular smooth muscle cells, and murine cardiomyocytes at the Z-discs, costameres, and intercalated discs [ 32 ]. TRPA1 is also activated by ROS, methylglyoxal, hydrogen peroxide, Ca 2+ , and prostaglandins [ 33 , 34 ], suggesting an interaction between TRPA1 and TRPV1.…”