The Injured Endothelium:
How it lays the groundwork for plaque growth—
And how to put a stop to it!
The endothelium is the single-celled layer
lining the arteries of the body. In fact, it’s the most extensive
organ system in the human body. It’s also a recipient of the abuse
our bodies receive, a fragile organ that injury transforms into a
plaque-lined landmine.
Endothelial injury precedes real trouble by years. Here’s how to
recognize when you have it and nutritional supplements and health
strategies to help correct it.
Vascular health from the inside-out
The paper-thin, barely visible
endothelium is a marvelously complex organ that lines the body’s
entire network of arteries and veins from the heart to the smallest
capillary in your fingertips. This single-celled layer maintains the
fluid nature of flowing blood, triggers blood clotting when needed,
cell adhesion, and transmits inflammatory signals.
The endothelium is also the traffic cop of the vascular system,
regulating arterial tone and maintaining a balance between
constriction and dilation, thereby controlling the ebb and flow of
blood to various organs. To do this, endothelial cells manufacture
regulatory proteins such as selectins, vascular cell adhesion
molecule-1 (VCAM-1), von Willebrand factor (vWF), and thrombomodulin.
Any disruption in the delicate balance triggers endothelial cells to
transform into an active state. Oxidized LDL particles, for
instance, or even a greasy cheeseburger, spark an increase in
protein production and arterial tone. Activation is transient, with
a return to basal conditions within hours to days. But if triggers
of endothelial activation are persistent or repetitive, the
endothelium can develop signs of permanent dysfunction. A cascade of
events ensues: inflammatory white blood cells bind to the
endothelial surface, migrate into the arterial wall, and, in turn,
lay the groundwork for growth of atherosclerotic plaque. If
activation continues, ultimately heart attack and stroke result.
Awareness of the endothelium as a vulnerable organ system has
unlocked a panorama of new preventive approaches. Because
dysfunction of the endothelium precedes overt coronary or other
vascular disease by years, correction of endothelial dysfunction
potentially permits you to engage the process before it unravels.
“A healthy endothelium is like Teflon, a nonstick surface that
enhances the flow of blood. By contrast, an unhealthy endothelium is
like Velcro, with white blood cells and platelets sticking to it.
When the lining of the blood vessel in healthy cells don’t stick,
clots don’t form, arteries don’t harden, and you won’t die of a
heart attack or stroke.”
Dr. John Cooke
Stanford University
Endothelial dysfunction—an everyday phenomenon
Conventional notions of arterial health received a
jolt when it was recognized that endothelial dysfunction is an
everyday phenomenon shared by common disorders like hypertension and
high cholesterol. Even something like eating a high-fat, processed
fast food restaurant meal can yield transient evidence of
dysfunction.1
Restoration of normal endothelial capacity can reverse the earliest
phases of arterial disease. Correction of endothelial dysfunction
can also be a strategy for health in advanced phases of disease once
atherosclerotic plaque has been detected (heart scan, carotid scan,
a stent has been implanted, a heart attack or stroke has occurred,
etc.).
Endothelial dysfunction is also a phenomenon of aging, a result of
“wear and tear”, affecting everyone after age 60.2
Righting the phenomena gone awry in endothelial health may provide
interesting strategies for maintenance of both health and youth.
Nitric oxide—a prizewinning molecule
In 1980, Dr. Robert Furchgott of the State
University of New York was conducting experiments using rabbit
arteries. He inadvertently stumbled on the observation that arteries
constricted when their inner lining—the endothelium—was removed, but
dilated when the lining was left intact. Dr. Furchgott theorized
that the endothelium was necessary to permit normal arterial
dilatation, and that damaged endothelium prevented it.
This sparked a furious effort to identify the factor produced by the
endothelium governing relaxation. Originally dubbed
"endothelium-derived relaxation factor," or EDRF, identification of
EDRF proved elusive, as it was present for mere seconds.
Nonetheless, in 1986 EDRF was discovered to be nitric oxide. This
discovery resulted in the Nobel Prize for Medicine awarded to Drs.
Furchgott, Louis Ignarro, and Ferid Murad in 1998. Nitric oxide is
now recognized to be a signaling molecule for many processes and the
single most powerful artery dilating agent known.3,4
Because endothelial tissue is just a single cell-layer thick, you
might be tempted to believe there is not much margin for error when
it comes to keeping it healthy. Although the endothelium is a
razor-thin line of demarcation between blood and tissues, it is
without doubt one of the body’s most tireless workhorses.
Industrious, and if anything overachieving, endothelial tissue is
responsible for keeping our bodies supplied with nitric oxide. With
the help of an enzyme called endothelial NO synthase, endothelial
cells function as the power plant where NO—a renewable resource
essential to good health—is manufactured and mobilized.
Dr. Louis J. Ignarro
Nobel Laureate in Medicine, 1998
The identification of nitric oxide as the pivotal molecule for arterial control has launched a worldwide scramble to develop strategies to increase the body’s capacity for its production.
Endothelial injury—the first step
The combination of coronary heart disease and
stroke is responsible for 38% of all deaths in the U.S. with costs
approaching $400 billion dollars. (American Heart Association, Heart
Disease and Stroke Statistics Update, 2005.) You might say that
diseases of the endothelium are therefore the number one killer of
Americans.
Injury to the delicate endothelium can assume many faces. The
endothelium is acutely sensitive to foods you eat, blood pressure,
and toxic substances in the blood like LDL cholesterol particles and
homocysteine.
Endothelial injury is measurable as a dysfunctional response to a
variety of dilating substances. Just as in Dr. Furchgott’s
groundbreaking experiments, administration of specific agents
triggers an artery to dilate when the endothelium is healthy. When
the endothelium is dysfunctional, the artery constricts.
In the heart, the coronary arteries normally dilate with exercise,
allowing a deluge of blood to nourish heart muscle and satisfy the
surge in oxygen demand. But in the presence of dysfunctional
endothelium, coronary arteries surrender the normal capacity to
dilate. Instead, they constrict. Repetitive, sustained constriction
results in damage to the endothelium, laying the foundation for
plaque formation.
Endothelial dysfunction can be assessed in living persons. A common
technique is to examine the easily accessible forearm (brachial)
artery with ultrasound. Maneuvers such as occlusion of the brachial
artery with a blood pressure cuff inflated to maximum pressure for
several minutes can be used to uncover endothelial dysfunction.
After the period of (painful!) occlusion and release of the cuff,
normal endothelium allows enlargement of the artery (often 10% or
more). No increase or outright constriction is seen when unhealthy
endothelium is present.5
Endothelial dysfunction is one of the fundamental phenomena behind
high blood pressure. (If you have high blood pressure, you
definitely have dysfunctional endothelium. If you don’t have high
blood pressure, you may still have dysfunctional endothelium.) It is
also behind diverse processes like stroke, eclampsia (of pregnancy),
headaches, aneurysm formation, and erectile dysfunction.
An injured and dysfunctional endothelium is the initial step in
creating the atherosclerotic plaque of coronary, carotid, and other
arteries. Endothelial dysfunction can precede the appearance of
visible atherosclerosis by decades.5
9 ways to correct endothelial dysfunction
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