01/03/2011 - Articles

The Inner Layer Of Your Aging Blood Vessels Is A Battlefield - Part XI

By: Ed G. Lakatta, MD

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In article 10 of this Series, "How Badly Are Your Arteries Hardening With Aging?" we discussed large artery structure and function, and we explained why vascular aging is a risk factor for high blood pressure.

To read this article with accompanying illustrations, as well as all the articles in the series, you can go to the mini-site: "Aging of Your Heart and Blood Vessels is Risky" by clicking here .

Introduction

In article #10 of this Series, "How Badly Are Your Arteries Hardening With Aging?" we discussed large artery structure and function, and we explained why vascular aging is a risk factor for high blood pressure.

We also told you how you could assess your individual vascular stiffness (hardening) by determining your pulse pressure from your blood pressure numbers (systolic minus diastolic). In this article we will show you that in addition to vascular hardening, other risky changes occur within blood vessels with aging. Presently these changes are NOT LABELED AS A MEDICAL CONDITION, but they play a role as a risk factor in a severe condition called atherosclerosis. And, they may be related to vascular stiffening as well.

The Vascular Intima and Function of The Endothelial Cells

In addition to the arteries themselves becoming stiffer with aging, the inner most of the arteries' three layers, the intima, becomes thickened. Refer to the following illustration as we discuss this process.

The three layers of the arterial wall are, from outside to inside, the adventia , the media and the intima . A flat layer of cells, called endothelial cells , forms a boundary between the blood in the lumen, or cavity, and the innermost layer of the arterial wall. Beneath the inner surface of the endothelial cell layer lies a sub endothelial space, which is separated from the vascular media by a basement membrane. Thus, the intima is composed of three components: endothelial cells, the sub endothelial space and the basement membrane. A vital function of the endothelial cells, because of their position and composition, is to form a barrier to prevent certain substances from the blood from entering the vessel wall. Another specialized function of these endothelial cells is to react to mechanical forces such as blood pressure, and blood flow generated by the heart's action. Endothelial cells react by releasing substances into the vessel wall that act on the vascular smooth muscle cells in the middle layer (media) of the arterial wall. You may recall that these smooth muscle cells contain contractile proteins that change their configuration in order to bring about a shortening, or contraction, of the cell. (Article 8 "Messages Transmitted From the Brain Fine Tune The Heart" .) This action changes the tone, or firmness, of these vascular smooth muscle cells. When endothelial cells sense an injury signal they produced other substances that signal vascular muscle cells to change their "nature". In response to such signals the vascular muscle cells dismantle their contractile machinery, begin to produce their own substances, and march toward the site of vascular injury in the inner area of the intima where they reposition themselves just beneath the endothelial cell layer. In reaction to injury endothelial cells also produce substances that signal to circulating blood cells, making it easy for these cells to stick to the endothelial cells, instead of flowing through the vessel smoothly.

Functions of Endothelial Cells

  • Form a barrier to prevent some substances from entering arterial wall
  • Sense mechanical forces (pressure and/or flow) and release substances which act to change the "contractile tone" of myocytes in medial layer.
  • Sense vascular injury: a. produce substances to change the "nature" of vascular muscle cells causing them to migrate to the area of injury ; b. signal blood cells to stick to endothelial cells

What Happens To The Inner Layer Of Your Arteries As You Become Older?

The lifetime of an endothelial cell is not infinite, and these cells, like those of your bowel, continuously multiply. However, with advancing age some of these specialized functions of the endothelial cell discussed above become blunted. The self-renewal process weakens. The endothelial barrier becomes leaky. Signals to vascular smooth muscle cells to regulate their function become altered. Vascular smooth cells as if perceiving endothelial injury migrate to the intima, multiply there and produce collagen, a matrix protein, and other molecules. The addition of these cells and matrix within the sub endothelial space results in intimal thickening. The intima of older arteries becomes a battleground where multiple reactions occur that are similar to a process of chronic injury. This battleground that occurs with aging provides fertile soil in which the seeds of a disease process called atherosclerosis flourish.

The Atherosclerotic Process

With advancing age, as the above changes are occurring within the blood vessel wall, other "intruders" enter into the battle. These "intruders" are constituents of the atherosclerotic process, which has some aspects in common with the aging process. However, unlike the aging process within blood vessels per se, atherosclerosis includes cholesterol accumulation and recruitment of other blood cells to join the battle; these are called inflammatory cells.

Atherosclerosis is so common in older persons (at least one out of two persons over sixty five years of age has atherosclerosis) that some experts had previously thought it was part of the "normal aging process". An alternate view is that atherosclerosis is a disease process that takes advantage of the previously discussed changes that occur within the artery with aging. The vascular aging process and the atherosclerotic process become intertwined as we age, and they influence each other. The more severe your vascular aging process, the easier it is for atherosclerosis to take hold; the more severe your atherosclerosis, the bigger its impact on vascular aging. Thus, it appears that the atherosclerosis process and the aging process combine forces to enable the disease called atherosclerosis to be more visible and more severe in older persons.

Atherosclerosis begins with changes in endothelial cell function that cause white blood cells moving through the blood to stick to the endothelial cells instead of flowing by normally. The barrier normally formed between endothelial cells and the blood becomes weakened and both blood cells and substances circulating in the blood pass through the endothelial cell barrier to join the battleground in the vessel's sub-endothelial space of the intimal compartment. Lipid or fat cell-like substances such as cholesterol in the blood then accumulate there. The lipids become "oxidized" and this enables them to signal the endothelial cells, which then alert others that the battle has begun. Smooth muscle cells that react to endothelial cells and to the fatty infiltration then join in. The smooth muscle cells march from their normal residence in the vascular media and invade the basement membrane by secreting enzymes, which attack the protein in the membrane. Depending on an individual's risk factors (life style variables such as a poor diet, lack of exercise, smoking, high blood pressure and the aging process itself) fat accumulation continues and the atherosclerotic process accelerates. White blood cells called macrophages then enlist in the battle and invade the area to digest the fat. Vascular smooth muscle cells that are resident in the intima and that have already changed their nature also scavenge the fat. These fat-laden white blood cells and vascular smooth muscle cells become known as "foam cells" . Vascular smooth muscle cells also try to curtail the injury by producing collagen, which forms a cap over the injury site. This fibrous cap is a weapon against disaster, just like scar formation in a wound. Then calcium accumulates and forms a material resembling bone. This complex array of foam cells, calcification, and lipid accumulation it is called an "atherosclerotic plaque". This plaque grows and becomes similar to an armed bomb. As the war progresses the fibrous cap weakens and ruptures due to the action of enzymes called proteases. The plaque cap can explode or rupture, thus exposing the plaque contents to the blood. The "detonation" gives the signal for the "special forces". These are blood cells called platelets. The platelets accumulate, resulting in a blockade, or blood clot on the inner surface of your blood vessel wall. This clot called a "thrombus" can become surprisingly large and occlude the vessel. By this mechanism of rupturing, even small plaques can interfere with blood flow.

Alternatively, atherosclerotic plaques can enlarge to such a degree as to completely block blood flow. When blood flow within an artery is severely compromised by either a larger plaque or a thrombus or both, the cells of your body organs that depend upon blood flow from that artery becomes damaged or die. This is similar to an enemy cutting off your food supply. Coronary atherosclerosis cuts off the heart's blood supply by occluding the heart's arteries and thus stopping the oxygen supply to the heart, causing a heart "attack" or myocardial infarction. A stroke results when the atherosclerosis processes cut off the oxygen supply to the brain.

The Battle is Not Over Yet

You can join in the battle occurring within you arteries by (1) becoming aware of the risk factors that increase the likelihood for atherosclerosis to occur and that determine its severity and (2) by taking steps required to reduce these risk factors. The most widely recognized risk factors are controllable risk factors. These are high blood pressure,high blood cholesterol, cigarette smoking, diabetes, obesity and lack of exercise.Newer risk factors continue to be identified.

Unfortunately age itself has been identified as the major risk factor for atherosclerosis. It is becoming clear that the risk conferred by age is attributable in large measure to the vascular aging process described above. Some doctors are now beginning to realize this and research is underway to design drugs that will combat the vascular aging process, which as noted above, is not identical with atherosclerosis, but intertwined with atherosclerosis as time goes by. Fortunately, like atherosclerosis, the vascular aging process can be impacted by exercise and perhaps diet. We will discuss how healthy aging, via exercise and a proper diet, can reduce your risk for atherosclerosis in an upcoming article.

Dr. Ed is a physician/scientist, who is internationally recognized for studies that range from humans to molecules on how the heart and blood vessels work in health and disease as the body ages.

Links

  • To read this article with accompanying illustrations, as well as all the articles in the series, you can go to the mini-site: "Aging of Your Heart and Blood Vessels is Risky".
Created on: 09/21/2001
Reviewed on: 01/03/2011

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