A need for bananas? Dietary potassium regulates calcification of arteries

October 5, 2017, University of Alabama at Birmingham
Yabing Chen. Credit: UAB

Bananas and avocados—foods that are rich in potassium—may help protect against pathogenic vascular calcification, also known as hardening of the arteries.

University of Alabama at Birmingham researchers have shown, for the first time, that reduced dietary potassium promotes elevated aortic stiffness in a mouse model, as compared with normal-potassium-fed mice. Such in humans is predictive of heart disease and death from heart disease, and it represents an important health problem for the nation as a whole.

The UAB researchers also found that increased dietary potassium levels lessened vascular calcification and aortic stiffness. Furthermore, they unraveled the molecular mechanism underlying the effects of low or high dietary potassium.

Such knowledge of how cells in the arteries regulate vascular calcification emphasizes the need to consider dietary intake of potassium in the prevention of vascular complications of atherosclerosis. It also provides new targets for potential therapies to prevent or treat atherosclerotic vascular calcification and arterial stiffness.

A UAB team led by Yabing Chen, Ph.D., UAB professor of pathology and a Research Career Scientist at the Birmingham VA Medical Center, explored this mechanism of vascular disease three ways: living mice fed diets that varied in potassium, mouse artery cross-sections studied in culture medium with varying concentrations of potassium, and mouse vascular grown in culture medium.

Working from living mice down to molecular events in cells in culture, the UAB researchers determined a causative link between reduced dietary potassium and vascular calcification in atherosclerosis, as well as uncovered the underlying pathogenic mechanisms.

The animal work was carried out in the atherosclerosis-prone mouse model, the apoliprotein E-deficient mice, a standard model that are prone to cardiovascular disease when fed a high-fat diet. Using low, normal or high levels of dietary potassium—0.3 percent, 0.7 percent and 2.1 percent weight/weight, respectively, the UAB team found that the mice fed a low-potassium diet had a significant increase in vascular calcification. In contrast, the mice fed a high-potassium diet had markedly inhibited vascular calcification. Also, the low-potassium mice had increased stiffness of their aortas, and high-potassium mice had decreased stiffness, as indicated by the arterial stiffness indicator called pulse wave velocity, which is measured by echocardiography in live animals.

The different levels of dietary potassium were mirrored by different blood levels of potassium in the three groups of mice.

When researchers looked at arterial cross-sections in cultures that were exposed to three different concentrations of potassium, based on normal physiological levels of potassium in the blood, they found a direct effect for the potassium on within arterial rings. Arterial rings in low-potassium had markedly enhanced calcification, while high-potassium inhibited aortic calcification.

"The findings have important translational potential," said Paul Sanders, M.D., professor of nephrology in the UAB Department of Medicine and a co-author, "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."

Mechanistic details

In cell culture, low potassium levels in the culture media markedly enhanced calcification of vascular smooth muscle cells. Previous research by several labs including Chen's group has shown that calcification of vascular smooth muscle cells resembles the differentiation of bone cells, which leads to the transformation of smooth muscle cells into bone-like cells.

So the UAB researchers tested the effect of growing vascular smooth muscle cells in low-potassium cell culture. They found that the low-potassium conditions promoted the expression of several gene markers that are hallmarks of bone cells, but decreased the expression of vascular smooth muscle cell markers, suggesting the transformation of the vascular smooth muscle cells into bone-like cells under low-potassium conditions.

Mechanistically, they found that low-potassium elevated intracellular calcium in the vascular smooth muscle cells, via a potassium transport channel called the inward rectifier potassium channel. This was accompanied by activation of several known downstream mediators, including protein kinase C and the calcium-activated cAMP response element-binding protein, or CREB.

In turn, CREB activation increased autophagy—the intracellular degradation system—in the low-potassium cells. Using autophagy inhibitors, the researchers showed that blocking autophagy blocked calcification. Thus, autophagy plays an important role in mediating calcification of vascular smooth muscle induced by the low-potassium condition.

The roles of the CREB activation and autophagy signals were then tested in the mouse artery cross-section and living-mouse models, with low, normal or high levels of potassium in the media or diet. Results in both of those systems supported the vital role for potassium to regulate vascular through calcium signaling, CREB and autophagy.

Besides Chen and Sanders, co-authors of the paper, "Dietary regulates and arterial stiffness," published in JCI Insight, are Yong Sun, Chang Hyun Byon and Youfeng Yang, UAB Department of Pathology; Wayne E. Bradley, Louis J. Dell'Italia and Anupam Agarwal, UAB Department of Medicine; and Hui Wu, UAB Department of Pediatric Dentistry. Sanders, Agarwal and Chen are also members of the Research Department, Veterans Affairs Birmingham Medical Center.

Explore further: Higher dietary potassium to sodium ratio can lower CVD risk

More information: Yong Sun et al, Dietary potassium regulates vascular calcification and arterial stiffness, JCI Insight (2017). DOI: 10.1172/jci.insight.94920

Related Stories

Higher dietary potassium to sodium ratio can lower CVD risk

February 28, 2017
(HealthDay)—Higher dietary potassium seems to be associated with reduced blood pressure, regardless of sodium intake, with the postulated mechanism involving the distal tubule sodium chloride cotransporter (NCC), according ...

Fruits and vegetables' latest superpower? Lowering blood pressure

April 5, 2017
Eating potassium-rich foods like sweet potatoes, avocados, spinach, beans, bananas—and even coffee—could be key to lowering blood pressure, according to Alicia McDonough, PhD, professor of cell and neurobiology at the ...

Cellular calcium handling in diabetes

September 29, 2017
Tight regulation of calcium levels in the endoplasmic reticulum (ER) – a cellular organelle with multiple functions – contributes to insulin secretion by pancreatic beta cells. Although ER calcium handling is perturbed ...

Muscle weakness studies suggest possible therapeutic strategies

January 20, 2015
A recently published study by a University of Colorado School of Medicine researcher and her colleagues suggests potential therapies for central core disease, a condition that can delay development of motor skills such as ...

High dietary sodium and potassium may worsen chronic kidney disease

September 17, 2015
High dietary intake of sodium and potassium may speed the progression of kidney disease, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings could ...

Ca2+, the intercellular signal in arterioles

July 4, 2017
Vasoconstriction must be balanced with vasodilation, particularly in the arterioles that supply tissues with blood. Endothelial cells protrude through holes in the internal elastic lamina in arterioles to make contact with ...

Recommended for you

It's not just for kids—even adults appear to benefit from a regular bedtime

September 21, 2018
Sufficient sleep has been proven to help keep the body healthy and the mind sharp. But it's not just an issue of logging at least seven hours of Z's.

Most nations falling short of UN targets to cut premature deaths from chronic diseases

September 21, 2018
People in the UK, US and China have a higher risk of dying early from conditions like cancer, heart disease and stroke than people in Italy, France, South Korea and Australia.

Patient-centered visual aid helps physicians discuss risks, treatments with parents

September 21, 2018
A series of illustrations and charts designed as decision aids for parents of children with minor head injuries helped them communicate with emergency medicine physicians and make informed decisions about their child's care, ...

Alcohol responsible for one in 20 deaths worldwide: WHO

September 21, 2018
Alcohol kills three million people worldwide each year—more than AIDS, violence and road accidents combined, the World Health Organization said Friday, adding that men are particularly at risk.

Study reveals a promising alternative to corticosteroids in acute renal failure treatment

September 21, 2018
A protein produced by the human body appears to be a promising new drug candidate to treat conditions that lead to acute renal failure. This is shown by a study conducted at São Paulo State University (UNESP) in São José ...

Smart pills dumb down medical care, experts warn

September 21, 2018
Enthusiasm for an emerging digital health tool, the smart pill, is on the rise but researchers at the University of Illinois at Chicago have published a paper in the American Journal of Bioethics that cautions health care ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.