The role of Transmembrane Protein 16A (TMEM16A) in pulmonary hypertension

Yuan, Ludong; Tang, Yuting; Yin, Leijing; Lin, Xin; Luo, Zhengyang; Wang, Shuxin; Li, Jing; Liang, Pengfei; Jiang, Bimei

doi:10.1016/j.carpath.2023.107525

Cited by 1 publication

(1 citation statement)

References 87 publications

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“…The role of TMEM16A in systemic and pulmonary hypertension has been recently reviewed [ 12 , 78 , 79 , 80 ], and some key studies are described above. In general, mean arterial pressure in the long-term (hours to days) is mainly modulated by renal pressure natriuresis and diuresis, and associated modulation of cardiac preload and output.…”

Section: Implications For Therapymentioning

confidence: 99%

The TMEM16A channel as a potential therapeutic target in vascular disease

Al-Hosni,

Kaye,

Choi

et al. 2024

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review The transmembrane protein 16A (TMEM16A) Ca2+-activated Cl− channel constitutes a key depolarising mechanism in vascular smooth muscle and contractile pericytes, while in endothelial cells the channel is implicated in angiogenesis and in the response to vasoactive stimuli. Here, we offer a critical analysis of recent physiological investigations and consider the potential for targeting TMEM16A channels in vascular disease. Recent findings Genetic deletion or pharmacological inhibition of TMEM16A channels in vascular smooth muscle decreases artery tone and lowers systemic blood pressure in rodent models. Inhibition of TMEM16A channels in cerebral cortical pericytes protects against ischemia-induced tissue damage and improves microvascular blood flow in rodent stroke models. In endothelial cells, the TMEM16A channel plays varied roles including modulation of cell division and control of vessel tone through spread of hyperpolarisation to the smooth muscle cells. Genetic studies implicate TMEM16A channels in human disease including systemic and pulmonary hypertension, stroke and Moyamoya disease. Summary The TMEM16A channel regulates vascular function by controlling artery tone and capillary diameter as well as vessel formation and histology. Preclinical and clinical investigations are highlighting the potential for therapeutic exploitation of the channel in a range of maladaptive states of the (micro)circulation.

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