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How too little potassium may contribute to cardiovascular disease

The aortas, the largest arteries, of mice fed a low-potassium diet (top row), normal diet (middle) and high-potassium diet (bottom). Calcification is shown in red in the right column.Chen lab, JCI Insight

Potassium is a mineral that is essential for health. A healthy diet usually provides enough potassium, but problems sometimes develop because too much sodium in the diet or certain medicines can increase the need for it. Previous studies have shown that increasing potassium intake can reduce the risk of cardiovascular diseases, such as high blood pressure, heart disease, and stroke. However, the mechanism is not known.

One explanation is that potassium might prevent vascular calcification, the buildup of calcium in the smooth muscle cells within arteries. Vascular calcification contributes to atherosclerosis, also known as hardening of the arteries. This is a serious disease in which plaques of fat, cholesterol, calcium, and other substances can diminish blood flow.

A research team led by Dr. Yabing Chen at the University of Alabama at Birmingham and the Birmingham VA Medical Center set out to discover how dietary potassium affects the vascular calcification process. The study was supported in part by the NIH’s National Heart, Lung, and Blood Institute (NHLBI) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Results were published on October 5, 2017, in JCI Insight.

For 30 weeks, the researchers fed three groups of atherosclerosis-prone male mice a high-fat, high-cholesterol diet that contained normal, low, or high levels of potassium. Using tissue staining and ultrasound imaging methods, the team showed that mice fed a low-potassium diet had increased vascular calcification and artery stiffness. Conversely, a high-potassium diet reduced calcification and stiffness. Using smooth muscle cell cultures, the team confirmed that low potassium enhanced vascular calcification, and high potassium inhibited it.

Next, the research team analyzed changes in proteins made by vascular smooth muscle cells when the potassium level was low. They found large increases in proteins often associated with bone cells and decreases in those associated with smooth muscle cells. This rise in bone-associated proteins suggests that low potassium directly affects the calcification of smooth muscle cells.

The team also showed that low potassium increased the calcium level within smooth muscle cells. Higher levels of calcium led to activation of a protein called CREB (cAMP response element-binding protein). Smooth muscle cell calcification could be blocked by inhibiting the activity of CREB. This suggested that CREB is a critical part of the calcification process when the potassium level is low. CREB activation was linked to increased autophagy, the process by which waste within the cell is broken down and recycled. Further work will be needed to define the role of autophagy in vascular calcification and artery stiffness.

“The findings have important translational potential,” says coauthor Dr. Paul W. Sanders of the University of Alabama at Birmingham, “since they demonstrate the benefit of adequate potassium supplementation on prevention of vascular calcification in atherosclerosis-prone mice, and the adverse effect of low potassium intake.”

—by Geri Piazza