The publicity materials and paper linked below discuss the identification of a cell type and related mechanisms responsible for calcification of blood vessels. The focus is on the environment of kidney disease, and thus on kidney tissue, but we might hope that this has a broader relevance to the age-related calcification that occurs in all blood vessels over the years. The more that is known of blood vessel calcification, the better the odds that something might be done about it soon enough to matter for you and I. The deposition of calcium in blood vessel walls is considered to be an important contribution to the loss of elasticity in these tissues. The stiffening of blood vessels with age drives the development of hypertension, an increase in blood pressure. Hypertension and stiffening cause detrimental remodeling of heart tissue that leads towards heart failure, as well as ever greater breakage of tiny blood vessels, such as in the brain, where the resulting tissue damage produces cognitive decline. Most forms of age-related cardiovascular dysfunction are exacerbated by hypertension: the higher the blood pressure, the worse the long-term prognosis.
While calcification in blood vessels is universally agreed to be a bad thing for the reasons given above, it is one of the many age-related changes for which there is no robustly defended line that can be drawn, leading through clearly demarcated steps, starting from an increase in fundamental forms of cell and tissue damage, the wear and tear caused by the normal operation of our biology, and ending with an increase in calcification. There is, however, a fair amount of evidence that can be used to argue over whether or not calcification is itself a fundamental form of damage, whether or not it is secondary to other forms of damage and change, and the nature of the processes that cause it. For example, calcification may be made worse by the presence of metabolic waste, of a type that the SENS Research Foundation has worked on clearing. It is also argued to be made worse by inflammation and by destruction of elastin, the basis for tissue elasticity. Sedentary individuals exhibit more calcification, as do those who report more time spent sitting.
The best path to deal with calcification depends on whether or not it is a fundamental form of damage. If it is a downstream effect of the classes of molecular damage outlined in the SENS vision for rejuvenation therapies, then the fix for calcification, as for near all aspects of aging, is to build those therapies, capable of repairing the root cause molecular damage. If calcification has a cellular cause, in that specific types of cells are changing their behavior in increasing numbers to deposit calcium where they should not be depositing calcium, then that scenario makes it much more likely that this is a secondary or later effect of other molecular damage. This unwanted change in cell behavior has been seen by other researchers in recent years, in heart tissue, for example. Separately, various therapeutic approaches based on removing the calcium deposits have been suggested by research groups over the years. It is likely that these approaches would be needed in addition to damage repair for people who have already grown old; simply repairing other forms of damage may not lead to the removal of excess calcium that has already accumulated. On this front it has been suggested to make use of osteoclasts, the cells responsible for dismantling bone, or, more conventionally, some form of chelation.
Scientists have implicated a type of stem cell in the calcification of blood vessels that is common in patients with chronic kidney disease. The research will guide future studies into ways to block minerals from building up inside blood vessels and exacerbating atherosclerosis, the hardening of the arteries. "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."
The cells implicated in clogging up blood vessels with mineral deposits live in the outer layer of arteries and are called Gli1 positive stem cells. They have the potential to become different types of connective tissues, including smooth muscle, fat and bone. In healthy conditions, Gli1 cells play an important role in healing damaged blood vessels by becoming new smooth muscle cells, which give arteries their ability to contract. But with chronic kidney disease, these cells likely receive confusing signals and instead become a type of bone-building cell called an osteoblast, which is responsible for depositing calcium. "We expect to find osteoblasts in bone, not blood vessels. 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. We found Gli1 cells in the the calcified aortas of patients in exactly the same place we see these cells in mice. This is evidence that the mice are an accurate model of the disease in people."
Further supporting the argument that Gli1 cells are driving the calcification process, the researchers showed that removing these cells from adult mice prevented the formation of calcium in their blood vessels. "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."
Mesenchymal stem cell (MSC)-like cells reside in the vascular wall, but their role in vascular regeneration and disease is poorly understood. Here, we show that Gli1+ cells located in the arterial adventitia are progenitors of vascular smooth muscle cells and contribute to neointima formation and repair after acute injury to the femoral artery. Genetic fate tracing indicates that adventitial Gli1+ MSC-like cells migrate into the media and neointima during atherosclerosis and arteriosclerosis in ApoE-/- mice with chronic kidney disease. Our data indicate that Gli1+ cells are a major source of osteoblast-like cells during calcification in the media and intima. Genetic ablation of Gli1+ cells before induction of kidney injury dramatically reduced the severity of vascular calcification. These findings implicate Gli1+ cells as critical adventitial progenitors in vascular remodeling after acute and during chronic injury and suggest that they may be relevant therapeutic targets for mitigation of vascular calcification.