The Role of Transmembrane protein 16A (TMEM16A) in Pulmonary hypertension

Elsevier

Available online 11 February 2023, 107525

Cardiovascular PathologyAuthor links open overlay panel, , , , , , , , Abstract

TMEM16A, a member of the TMEM16 family, is the molecular basis of Ca2+-activated chloride channels (CaCCs) and is involved in a variety of physiological and pathological processes. Previous studies have focused more on respiratory-related diseases and tumors. However, recent studies have identified an important role for TMEM16A in cardiovascular diseases, especially in pulmonary hypertension. TMEM16A is expressed in both pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs) and is involved in the development of pulmonary hypertension. This paper presents the structure and function of TMEM16A, the pathogenesis of pulmonary hypertension, and highlights the role and mechanism of TMEM16A in pulmonary hypertension, summarizing the controversies in this field and taking into account hypertension and portal hypertension, which have similar pathogenesis. It is hoped that the unique role of TMEM16A in pulmonary hypertension will be illustrated and provide ideas for research in this area.

Section snippetsThe TMEM16 family of membrane proteins and TMEM16A

The TMEM16 (Transmembrane protein 16) family of membrane proteins is also known as the Anoctamin (ANO) family. The TMEM16 family contains 10 family members, TMEM16A to TMEM16K (ANO1-ANO10), except TMEM16I. Members of this family are subdivided into three sub-families TMEM16A/TMEM16B, TMEM16C/TMEM16D/TMEM16J, and TMEM16E/TMEM16F based on structural and functional similarities, and a unique branch, TMEM16G [1]. In addition, TMEM16H and TMEM16K in the TMEM16 family appear to have separated early

The definition of Pulmonary Hypertension

Pulmonary hypertension (PH) is a chronic and progressive disease that, like many other lung diseases, often leads to delays in diagnosis and therefore in optimal treatment [47]. Pulmonary hypertension is a major global health problem and is by no means uncommon. All age groups are affected, but it is more common in women, people aged 75 years or older, and Black individuals [48]. Current estimates suggest that the prevalence of pulmonary hypertension is about 1% of the global population, and in

The Inhibitors of TMEM16A

Since TMEM16A was shown to be the molecular basis of calcium-activated chloride channels, researchers have been working to find specific drugs that can modulate TMEM16A to provide help in the treatment of clinically relevant diseases. The current study suggests two different types of inhibitors of TMEM16A (Table 3), the first group is natural products, mainly represented by traditional Chinese medicine compounds, including Gallotannins, Tannic acid [72], Eugenol [73], Matrine [74], Plumbagin

Conclusion and prospect

Ion channels play essential roles in human physiology and toxicology. Cardiac contraction, neural transmission, temperature sensing, insulin release, regulation of apoptosis, cellular pH, and oxidative stress, as well as detection of active compounds from chili, are some of the processes in which ion channels have an important role. [90] Among ion channels, calcium-activated chloride channels (CaCCs) play a particularly important role in cellular physiology, including epithelial secretion of

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Figure 2, Table 2

Declaration of Competing Interest

The authors have no competing interests to declare that are relevant to the content of this article.

Acknowledgements

This study was supported by the grants from National Natural Science Foundation of China (No. 81971820).

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