Stem Cells Behind Calcified Blood Vessels in Kidney Disease Identified

The calcification of blood vessels is a serious effect in chronic kidney disease patients and they are found to have two to five times more risk for coronary artery calcification than healthy controls. This increases the risk for myocardial infarction as well as atherosclerosis. A new study by scientists from University School of Medicine in St. Louis at Washington have found that a particular type of stem cells are responsible for the calcification of the blood vessels in chronic kidney patients, raising hope for better control and care.

An associate professor of medicine and the director of the Division of Nephrology Dr. Benjamin Humphreys who is also the senior author of the study talks about the active process involved in the process “In the past, this calcification process was viewed as passive -- just mineral deposits that stick to the walls of vessels, like minerals sticking to the walls of water pipes. More recently, we've learned that calcification is an active process directed by cells. But there has been a lot of controversy over which cells are responsible and where they come from."

Vascular Calcification in Chronic Kidney Disease Patients

There are two types of calcification of the arteries that take place in chronic kidney disease patients.

A) Atherosclerotic calcification:

• This is present in the intimal layer
• Leads to atherosclerosis
• Causes cellular necrosis
• Deposition of lipids
• Inflammation
• Osteogenesis that includes induction of osteoblasts

B) Medial Artery Calcification:

• This type of calcification is found to be common in chronic kidney disease patients and people with diabetes.
• Occurs in the vascular smooth muscle cells.
• It is also known as Monckeberg Sclerosis.

Earlier it was believed that calcification of the arteries was a passive process but current studies point towards an active process. The passive process was believed to be due to an elevated serum phosphate levels and an increase in the product of serum calcium phosphate. This was thought to lead to an over saturation of the plasma.

Current studies are aimed at the association between vascular calcification and osteogenesis. In calcified medial arterial layers as well as in atherosclerotic plaques, there have been expression of key regulators of bone structural proteins.

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Gli1 Positive Stem Cells

Gli1 cells are adult stem cells that are present in the outer layer of the arteries. These stem cells have the ability to differentiate into a number of connective tissue like fat, bone and smooth muscle. The study by Dr. Benjamin Humphreys and colleagues has found that these stem cells are responsible for the mineral deposits that clog the arteries.

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Mechanism of Clogging

Gli1 cells are stem cells that are directed to generate smooth muscle cells in the arteries to enable healing and effective contractive ability of the arteries. In chronic kidney disease, this mechanism is disrupted with changes in signaling pattern resulting in these stem cells being converted into osteoblasts, which are a type of bone cells that increase the deposition of calcium in the arteries.

Dr Humphreys adds, "We expect to find osteoblasts in bone, not blood vessels. In the mice with chronic kidney disease, Gli1 cells end up resembling osteoblasts, secreting bone in the vessel wall. During kidney failure, blood pressure is high and toxins build up in the blood, promoting inflammation. These cells may be trying to perform their healing role in responding to injury signals, but the toxic, inflammatory environment somehow misguides them into the wrong cell type."

Tissue Studies:

The researchers from The University School of Medicine in St. Louis studied tissue samples of people who died from chronic kidney disease to understand the effects on the aorta. The scientists found that mineral deposits in the aorta of humans was found in the same place as those found in mice, suggesting the mice studies would be accurate in understanding the pathogenesis of this condition.

Mice Studies:

The researchers removed the adult stem cells Gli1 in mice and observed the deposition of calcium in their aorta. It was found that the there was no calcification of the aorta in mice.

Another study by researchers from Brigham and Women’s Hospital (BWH) ablated the Gli1 cells in mice with cardiac and kidney fibrosis, without harming any other cell. It was found that the there was a reduction in fibrosis with a rescue of the function of the heart.

Such studies point towards

• Gli1 being a possible target for drug therapy to lower calcification and to restore the functions of the organs.
• Cautious prescription of oral calcium for people on dialysis or with chronic kidney disease
• The Gli1 cells can be induced to produce smooth muscle cells which will aid in healing the blood vessels.

However, Dr Humphrey cautions "Now that we have identified Gli1 cells as responsible for depositing calcium in the arteries, we can begin testing ways to block this process. A drug that works against these cells could be a new therapeutic way to treat vascular calcification, a major killer of patients with kidney disease. But we have to be careful because we believe these cells also play a role in healing injured smooth muscle in blood vessels, which we don't want to interfere with."

A considerable number of individuals with chronic kidney disease die of atheroscleroses which can be avoided by effective targeted treatment such as targeting the Gli1 cells. Stems cells have always held an enviable position in medical studies and with the right kind of stimulation, the Gli1 cells reverted as healers rather than sealers.

References:

1. Vascular Calcification: The Killer of Patients with Chronic Kidney Disease - (http://jasn.asnjournals.org/content/20/7/1453.full)
2. Vascular calcification in chronic kidney disease - (http://www.ncbi.nlm.nih.gov/pubmed/16502129)
3. Researchers have identified the cells responsible for fibrosis, the buildup of scar tissue - (https://health-innovations.org/2014/12/02/researchers-have-identified-the-cells-responsible-for-fibrosis-the-buildup-of-scar-tissue/)

Source-Medindia