Enhancing veins for better dialysis access

In order to save a life, unnatural, direct connections between arteries and veins are made, such as a kidney dialysis access point or using a vein to get around a coronary artery blockage.

However, the vein, which is unaccustomed to and not really designed to handle the high volume, high pressure of the blood flowing through our arteries, can rapidly narrow in response, leading to the failure of the bypass graft or dialysis access point.

In order to ensure the veins' success for patients in their unfamiliar new role, Dr Xiaochun Long, a molecular biologist at the Medical College of Georgia at Augusta University, is working to literally strengthen the walls of these veins so they can perform more like arteries.

To support her research, Long recently received a $400,000 Established Investigator Award from the American Heart Association. Her goal is to eventually make the middle layer of veins, which are primarily made of a single layer of smooth muscle cells that give them shape and strength, more like the thicker middle of arteries, which are designed to withstand the pressure of the heart pumping blood into them.

According to Long, the vein will change once the artery and vein are connected. " In order to help the vein better adapt to the arterial dynamic, we want to help control the behaviour of smooth muscle cells.

We first need to better comprehend how the vein adapts in order to find ways to enhance how these arteriovenous fistulas, or AVF, for dialysis and bypass grafts for the heart mature", Long said.

Long and her team are aware that the blood vessel walls' smooth muscle cells play a crucial role in detecting the walls' stretching in response to elevated pressure and volume. But it's less clear what they do in response.

Early research from her lab suggests that the smooth muscle cells in the vein undergo a transition from their usual quiescent state to one of proliferation. Unexpectedly, smooth muscle cells maintain their ability to contract as they begin to change, according to Long. Smooth muscle cells are surprisingly less aggressive at contracting in the veins than they are in the arteries, where they continuously help push blood out to the body.

Her genome-wide studies have revealed two related genes that are crucial to the healthy maturation of the under-stress veins and are known to play a significant role in smooth muscle cell differentiation, which is essentially how smooth muscle cells are made from stem cells.

She has proof that myocardin-related transcription factors, or MRTF A and B (also known as MKL1 and 2), react to the newly discovered stretch by activating additional genes that allow the smooth muscle cells to multiply, differentiate, and organize. These genes are crucial in the early stages of the proper maturation of an AVF, for instance.

Conversely, a lack of these transcription factors prevents the smooth muscle cells from adequately shoring up the vein wall in response to the increased pressure. While some of these genes are expressed in veins, they are less so than in arteries, and Long claims that more of these genes must be produced at the proper time for veins to bulk up their smooth muscle layer.

With the new grant, she hopes to further explore how these important transcription factors work with other cell types, such as the endothelial cells that line blood vessels, to help smooth muscle cells and aid in vein maturation.

The research may one day result in treatments that increase the expression of genes necessary for a smooth transition.

Long is aware that these unnatural connections are possible because many people experience success with bypasses and fistulas. Furthermore, she has conducted studies directly relating the large jugular vein to the large carotid artery and observed vein walls strengthening as a result. According to her, genetics is probably a factor in why some people are able to make connections while others are not.

According to the National Kidney Foundation, an AVF is the best option for dialysis. It is surgically created with the goal of creating a long-term pathway for more blood to flow through the dialysis machine for cleaning during a dialysis session, and they are typically linked to lower infection rates.

However, a significant portion of newly formed fistulas are insufficiently mature and therefore useless. Diabetes, for example, can make failure more likely. It's a significant issue for both patients and caregivers, according to Long.

Studies show, for example, that about half of vein grafts for the heart fail 5 to 10 years after surgery and 20-40% within the first year. Veins from a patient's legs or heart are frequently used to bypass arterial blockages in these areas as part of the treatment of atherosclerosis.

The bottom line is that, in the case of heart bypass surgery, the veins can occlude, much like the blocked vessels they were used to bypass. More frequently, veins are essentially immune to the usual plaque buildup that is the leading killer in the country and the most common cause of heart disease.

The smallest blood vessels in the body, the capillaries, help slow blood flow and volume down before reaching the veins. This is similar to going from a four-lane road down to two lanes. Sharing oxygen and nutrients with the body's tissue is one of the main purposes of capillaries with thinner walls.

The tunica media, the middle and thickest layer of the three-layer artery wall, is primarily made up of vascular smooth muscle cells. In contrast, the vein wall has three thinner layers. The lumen, the vein's central passageway, is typically much larger. Long states that one of the issues is that the vascular smooth muscle cells in the arteries and veins are not exactly the same in their natural state. This is one of many things she wants to learn more about.

Blood vessels cannot contract without smooth muscle cells, according to Long, and they receive many of their instructions from the endothelial cells that line blood vessels and are in direct contact with the blood.

However, vascular smooth muscle cells can also be a factor in artery disease. They can once more change from their quiescent state to activation and begin migrating to the interior of the lumen in an apparent effort to aid in the healing of the artery in response to the early injury of atherosclerosis. Long and others have observed that the cells have instead turned into a primary cause of the illness. There is also proof that high blood pressure causes the vascular smooth muscle cells to change in a harmful way.

Arteriovenous fistulas or other malformations can develop on their own anywhere in the body, including the brain. In some cases, a procedure is necessary to help better secure or close the abnormal passageways, which are prone to rupture.