April 10, 2011
Atherosclerotic Plaque Forms In Short Period

Plaques that cause strokes and heart attacks form in just several years.

In a new study performed in humans, researchers from Karolinska Institutet have determined the age of atherosclerotic plaques by taking advantage of Carbon-14 (14C) residues in the atmosphere, prevailing after the extensive atomic bomb tests in the 50ties and 60ties. The findings, published in the scientific online journal PLoS ONE, suggest that in most people plaque formation occurs during a relatively short and late time period in life of 3-5 years.

This raises an obvious question: Why isn't plaque accumulation a long term process? What changes in the cardiovascular system that allows or causes a sudden acceleration in plaque formation? Do stem cells become too old to do repairs? Or do other cells suddenly change their behavior in ways that encourage plaque formation?

"We suspected that the plaque would be substantially younger than the patients, who were on average were 68 years old at surgery, but we were surprised when we found that the average age of these plaques was less than 10 years", says Associate Professor Johan Björkegren, who lead the study at the Department of Medical Biochemistry and Biophysics.

They found plaque age to be inversely correlated with plasma insulin. That makes sense. High insulin is associated with insulin-resistant diabetes which is, in turn, associated with many diseases including cardiovascular diseases. Eat a diet and get enough exercise to avoid insulin-resistant diabetes and reduce your risk of plaque formation, strokes, and heart attacks.

You can read the full article here.

An observed relationship between shorter chromosome telomere length (telomere caps shrink with age and are a biomarker for aging) and atherosclerosis suggests cellular aging somehow accelerates plaque formation. You can read one research paper that looked at telomere length and plaque formation for an interesting discussion of hypotheses on this topic. Possibly infusion of youthful endothelial cells into the walls of the vascular system will some day stop and possibly even reverse plaque formation. Here's another reason to wish for rapid development of cell therapies.

Share |      Randall Parker, 2011 April 10 03:07 PM  Aging Cardiovascular Studies

Neville72 said at April 10, 2011 4:10 PM:

Randall, You may be interested in this exciting heart-related stem cell research already being done with human subjects.



American Physiological Society

Roberto Bolli discusses cardiac stem cell treatment for heart failure at Cannon Lecture

WASHINGTON, DC – Heart failure affects roughly six million Americans, yet treatment consists of either a heart transplant or the insertion of mechanical devices that assist the heart. This is unacceptable to Roberto Bolli, MD, Chief of the Division of Cardiovascular Medicine at the University of Louisville in Louisville, Ky., which is why he is on a mission to make cardiac stem cell treatment an option for all who must cope with the limitations of a failing heart.

Dr. Bolli is conducting the groundbreaking study, "Cardiac Stem Cell Infusion in Patients with Ischemic cardiomyopathy (SCIPIO)," in which researchers at the University of Louisville's Jewish Hospital are collaborating with a team led by Piero Anversa, MD, at the Brigham and Women's Hospital in Boston to perfect a technique for using a patient's own cardiac stem cells to regenerate dead heart muscle after a heart attack.

In honor of his illuminating work, the American Physiological Society (APS) has selected Dr. Bolli to present the Walter B. Cannon Memorial Lecture at the Experimental Biology 2011 meeting (EB 2011). This lecture is the Society's pre-eminent award lecture and is designed to recognize an outstanding scientist for his or her contributions to the field.

A Tale of Two Proteins

The cardiac stem cell treatment investigated in the SCIPIO trial consists of isolating the patient's cardiac stem cells from part of the upper chamber of the heart (harvested during coronary bypass surgery) and expanding these cells in the lab. Four months after surgery, the cells are infused into scarred cardiac tissue by catheterizing a large artery in the patient's leg. Using the patient's own cardiac stem cells eliminates the possibility of rejection.

Besides SCIPIO, Dr. Bolli is also performing basic research aimed at on enhancing the cardiac stem cells while they are cultured in the lab for expansion. He is working with two proteins, heme oxygenase 1 (HO-1) and nitric oxide synthase (NOS). HO-1 is a protein made in response to cellular stress, such as oxidative stress or oxygen deficiency. It catalyzes the breakdown of heme, which is a molecular component of hemoglobin, the part of the red blood cell that transports oxygen around the body. When HO-1 breaks down heme, one of the by-products is carbon monoxide (CO). NOS, the other protein Dr. Bolli is investigating, is an enzyme that catalyzes the production of nitric oxide (NO). Dr. Bolli is focusing on these two proteins because their catalytic by-products, CO and NO, exert remarkable beneficial effects.

"When the heart muscle is dying because of a heart attack, these gases (CO and NO) are extremely cardioprotective and help the tissue survive," he says. "We are now applying these same proteins to stem cells, using the knowledge that we have gained from 20 years of research in cardioprotection."

A Promising Future

So far, the results are promising. "We have exciting data indicating that if we increase these proteins in stem cells, the stem cells become more resilient and more effective at repairing damage," Dr. Bolli says.

Even with natural cells (in which these proteins are not increased), such as those used in SCIPIO, the results are very encouraging. Improvements seen in patients who have received cardiac stem cell infusion include increased ejection fraction, the fraction of blood pumped through the two lower chambers of the heart. Patients also experience dramatic improvements in what they are able do physically, Dr. Bolli says. "There are people who are almost completely incapacitated, and after they get stem cells, they can do so much more. I have a patient who couldn't walk to the bathroom, and now he can walk two miles."

Dr. Bolli cautions that SCIPIO is a Phase 1 trial, meaning that it is the first round of testing in humans. Its primary purpose is to assess safety and feasibility, rather than efficacy. Yet, he remains optimistic and notes that cardiac stem cells offer the hope of healing the heart. "All of the other treatments currently available--transplants, assist devices, drugs--may prolong life but do not solve the problem. By regenerating new heart muscle, cardiac stem cells could actually solve the problem."

To date, 17 patients have received cardiac stem cells in the SCIPIO trial. Dr. Bolli will discuss his research and provide the latest details of how the patients are faring when he presents this year's Cannon Lecture, "The nitric oxide–carbon monoxide module: A fundamental mechanism of cellular resistance to stress," on Saturday, April 9, 5:45 pm ET at the Walter E. Washington Convention Center.

Walter B. Cannon Award Lecture

The Cannon Award lectureship, established in 1982, is the APS' highest award. The individual selected is an outstanding physiological scientist chosen by the President-Elect, with the consent of Council, to lecture on "Physiology in Perspective" during the plenary session of the Society's next annual meeting. At the 1984 fall meeting, the title of the presentation was changed to "Physiology in Perspective: The Walter B. Cannon Lecture."

Bruce said at April 10, 2011 6:19 PM:

I remember research done associating virueses with plaque.


Brett Bellmore said at April 10, 2011 6:22 PM:

That the variation in the age of plaques in a given patient was substantially less than the average age of the plaques suggests that the plaques form during an acute episode of some sort, perhaps an asymptomatic infection. If they were resulting from a monotonic deterioration in some aspect of the metabolism, you'd expect them to continue being produced once production was started.

It wouldn't be the first 'lifestyle' disease which was discovered to be due to an infection.

Lou Pagnucco said at April 11, 2011 10:36 AM:

This suggests a further question -

Since these plaques grow so quickly, are there any other (short half-life) radiolabelled substances with high affinity for growing plaques that could serve as a very early alert system for heart disease?

Maybe a pill of small amount of radiotracers and a geiger counter could replace CAT scans.

Earl the Pearl said at April 12, 2011 2:14 AM:

plaque is the bodies way of stabilizing weak artery linings in the cardiovascular system. Diets low in cholesterol force the body to up plaque production: problem is a high proportion of people believe that 80% grain diet is the way to go, this is false. I would be willing to bet that,
- these people when placed on a Paleo-esque diet, reduced carb (simple sugars, corn syrup) intake, etc. would show signs of improvement, both in liver function and in vascular repair.
- increase the intake of vegetables, leafy and green high in Vitamin K. Origins and effects of cholesterol helped discover its function.
(nice short summary: http://summittotalhealth.com/articles/view/the_forgotten_vitamin/
**Long version** http://westonaprice.org/abcs-of-nutrition/175-x-factor-is-vitamin-k2#summary )

Plaque was young? correlates to increase in corn syrup in all foods ... cause needs to be determined.

Axel said at April 13, 2011 7:15 AM:

@Lou Pagnucco I like your comments here. Do you have a blog I could follow? Thanks.

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