Source: Zhongshan School of Medicine
Edited by: Zheng Longfei, Wang Dongmei

Low serum Cl^- is a specific independent predictor of CVD mortality. However, the relationship between Cl^- and CVD risk remains unclear. Emerging evidence indicates that cerebrovascular remodeling has a long-term impact on cardiovascular function and is a major risk factor for stroke and stoke mortality.

Recently, the research group directed by Prof. Yongyuan Guan and Prof. Guanlei Wang from Zhongshan School of Medicine at Sun Yat-sen University revealed ClC-5 in BASMCs is a Cl^- sensor in vascular remodeling and regulates cell proliferation during hypertension progression. The work entitled “Low Chloride–Regulated ClC-5 Contributes to Arterial Smooth Muscle Cell Proliferation and Cerebrovascular Remodeling” has been published in Hypertension.

Previously, the research group demonstrated that low chloride stimuli evoked a ClC-5-dependent Cl^- current in basilar smooth muscle cells (BASMCs). They also showed that ClC-5 protein expression was positively correlated with basilar artery remodeling as hypertension progressed. They used 2-kidney, 2-clip, and angiotensin II infusion-induced hypertensive animal models, human artery samples, and ClC-5 knockdown and overexpression mice, and revealed that ClC-5 in arterial smooth muscle cells (SMCs) causes exaggerated vascular remodeling. The mechanism investigation identified ClC-5 facilitated cerebrovascular remodeling and BASMC proliferation via the WNK1/AKT cascade. This study disclosed that ClC-5 acts as a link between low chloride and vascular remodeling during hypertension. This work indicates that ClC-5 blockade may be a potential new therapeutic strategy for the prevention and treatment of cerebrovascular remodeling during hypertension and other cardiovascular disorders associated with low serum [Cl^-]o.


The research was co-authored by Min Gao from the Sixth Affiliated Hospital of Sun Yat-sen University, Mingming Ma and Fengting Lu from Zhongshan School of Medicine. Prof. Yongyuan Guan Prof. Guanlei Wang from Zhongshan School of Medicine and Prof. Binzhang from Guangdong Provincial People's Hospital were co-corresponding authors.

Link to the paper: https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.121.18472