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Dietary potassium regulates vascular calcification and arterial stiffness
Yong Sun, … , Hui Wu, Yabing Chen
Yong Sun, … , Hui Wu, Yabing Chen
Published October 5, 2017
Citation Information: JCI Insight. 2017;2(19):e94920. https://doi.org/10.1172/jci.insight.94920.
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Research Article Vascular biology

Dietary potassium regulates vascular calcification and arterial stiffness

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Abstract

Vascular calcification is a risk factor that predicts adverse cardiovascular complications of several diseases including atherosclerosis. Reduced dietary potassium intake has been linked to cardiovascular diseases such as hypertension and incidental stroke, although the underlying molecular mechanisms remain largely unknown. Using the ApoE-deficient mouse model, we demonstrated for the first time to our knowledge that reduced dietary potassium (0.3%) promoted atherosclerotic vascular calcification and increased aortic stiffness, compared with normal (0.7%) potassium–fed mice. In contrast, increased dietary potassium (2.1%) attenuated vascular calcification and aortic stiffness. Mechanistically, reduction in the potassium concentration to the lower limit of the physiological range increased intracellular calcium, which activated a cAMP response element–binding protein (CREB) signal that subsequently enhanced autophagy and promoted vascular smooth muscle cell (VSMC) calcification. Inhibition of calcium signals and knockdown of either CREB or ATG7, an autophagy regulator, attenuated VSMC calcification induced by low potassium. Consistently, elevated autophagy and CREB signaling were demonstrated in the calcified arteries from low potassium diet–fed mice as well as aortic arteries exposed to low potassium ex vivo. These studies established a potentially novel causative role of dietary potassium intake in regulating atherosclerotic vascular calcification and stiffness, and uncovered mechanisms that offer opportunities to develop therapeutic strategies to control vascular disease.

Authors

Yong Sun, Chang Hyun Byon, Youfeng Yang, Wayne E. Bradley, Louis J. Dell’Italia, Paul W. Sanders, Anupam Agarwal, Hui Wu, Yabing Chen

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Figure 1

Dietary potassium regulated vascular calcification and aortic stiffness in mice.

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Dietary potassium regulated vascular calcification and aortic stiffness ...
ApoE–/– mice (n = 9/group) were fed a high-fat diet containing normal potassium (Control), low potassium (Low K+) or high potassium (High K+) for 30 weeks. (A) Vascular calcification in aortic roots, determined by Alizarin red staining. Representative images of H&E staining and Alizarin red staining in consecutive aortic root sections. Scale bars: 500 μm. (B) Quantification of calcification in the aortic root sections, measured using ImageJ software. Results presented are the percentage of positively stained areas in the total atherosclerotic lesion area of aortic roots. Bar values are means ± SD. (C) Total calcium content in the descending aortas, quantified by the Arsenazo III method. Results shown are normalized by total protein amount. Bar values are means ± SD. (D) Effects of dietary potassium on aortic stiffness. Pulse wave velocity (PWV), an indicator for aortic stiffness, determined by echocardiography at the end of the experiments. Bar values are means ± SD. Statistical analysis was performed by 1-way ANOVA followed by a Student-Newman-Keuls test.

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