# The emerging role of anoctamin-1 in cardiac and cerebrovascular diseases

## TL;DR

ANO1, a calcium-activated chloride channel, plays a key role in heart and brain blood vessel diseases, and targeting it could lead to new treatments.

## Contribution

This review highlights ANO1's role in cardiocerebral vascular diseases and its potential as a therapeutic target.

## Key findings

- ANO1 dysfunction is linked to heart diseases, hypertension, and stroke.
- ANO1 inhibitors show promise as therapeutic agents for cardiac and cerebrovascular conditions.
- ANO1 is involved in vascular smooth muscle contraction and cardiac excitability.

## Abstract

Cardiocerebral vascular disease has long been the leading cause of morbidity and mortality worldwide. Although there are many effective avenues for preventing and treating cardiocerebral vascular disease, further research is still needed to identify more novel molecular targets for therapeutic intervention. Anoctamin-1 (ANO1), also known as transmembrane protein 16A (TMEM16A), is the molecular identity of calcium-activated chloride channels (CaCCs) and is widely distributed in myocardial cells and the vasculature, including but not limited to the thoracic aorta, mesenteric artery, cerebral artery, and portal vein. ANO1 has many functions in the cardiocerebral vascular system, including cardiac excitability, vascular smooth muscle contraction, and epithelial cell secretion. Aberrant expression or dysfunction of ANO1 is associated with several cardiocerebral vascular diseases, including myocardial ischaemia/reperfusion injury (MIRI), arrhythmias, cardiac fibrosis, hypertension, and stroke. Therefore, this review provides an overview of ANO1, including its structure, distribution, and activation mechanism, and highlights the current knowledge of ANO1 in the pathophysiological process of heart diseases, hypertension, and stroke. We also summarise the pharmacological regulatory target of ANO1, providing promising insights for applying ANO1 inhibitors as cardiac and cerebrovascular therapeutic agents.

Diagram illustrating the impact of ANO1 dysfunction on cardiovascular health. Left section shows a human torso highlighting the cardiovascular system with ANO1 dysfunction by a red arrow. Right section details effects: Heart diseases (MIRI, cardiac arrhythmia, fibrosis), Vascular remodelling (endothelial dysfunction, ECM deposition, VSMC autophagy, migration, proliferation), Hypertension (elevated blood pressure, vasoconstriction), and Stroke (BBB integrity damage, ischemia).