Endothelial dysfunction and
Dr Craige Golding
MBCHB (cum laude), FCP(SA) : Fellow of the College of Physicians of South Africa
ABAARM :American Academy Board Certified in Antiaging and Regenerative Medicine
FAAFM : Fellowship in Antiaging and Functional Medicine
he various forms of athero- As we age, some of the special- endothelial lesion. Fibrinogen may
sclerosis, including coronary ized functions of the endothelium contribute to plaque buildup or par-
thrombosis, stroke and pe- become blunted. The self renewal ticipate in blood clot-induced block-
ripheral arterial disease, continues process weakens, the endothelial age of an artery after an unstable
to be the leading cause of death barrier becomes leaky and signals atherosclerotic plaque ruptures.30
worldwide. Black Africans are to- to the middle wall smooth muscle Glucose at even high-normal
day too suffering from an increased cells that regulate their function levels may accelerate the glyca-
incidence of cardiovascular disease become altered. The vascular aging tion process that causes arterial
due to the adoption of a western process and atherosclerosis become stiffening, while high-normal fasting
lifestyle and diet. intertwined as we age. insulin inflicts direct damage to the
The endothelium (the largest endothelium.31-36
organ in the body) controls vascular The arterial wall under High levels of iron promote LDL
smooth muscle tone by secreting attack (excerpt lef October oxidation in the damaged endothe-
relaxing and contracting fac- 2005) lium, while low levels of testoster-
tors. There is a constant release High blood pressure, elevated LDL one appear to interfere with normal
of endothelium-derived relaxing and triglycerides, cigarette smok- endothelial function.9,11,14
factors (EDRFs), whose biologic ing, diabetes, obesity, and lack of C-reactive protein is not only
activity is provided by nitric oxide exercise contribute to endothelial an inflammatory marker, but also
(or similar molecules) and con- dysfunction and the subsequent de- directly damages the endothelium.
stantly counteracts vasoconstrictor velopment of atherosclerosis.15-25 Chronic inflammation, as evidenced
substances such as noradrenaline, Additional endothelial-damaging by persistent high levels of C-reac-
angiotensin II or endothelin I. The factors include excess levels of glu- tive protein, creates initial injuries
normal functioning endothelium cose, insulin, iron, homocysteine, to the endothelium and also ac-
is able to increase the release of fibrinogen, and C-reactive protein, celerates the progression of existing
EDRFs in response to physiological as well as low HDL and free testo- atherosclerotic lesions.3,27
stimuli, such as the stress exerted sterone (in men).3,9,10,24,26-28 In response to numerous published
by the circulating blood, or to Homocysteine is particularly dan- studies, health-conscious people are
humoral stimulation by vasoactive gerous because it can induce the altering their diets, taking drugs,
substances such as acetylcholine or initial injury to the endothelium. hormones, and dietary supplements,
bradykinin. The endothelium is in Homocysteine then facilitates oxida- and trying to exercise regularly in or-
effect both a target and a modula- tion of the fat/LDL that accumulates der to reduce these atherosclerosis
tor of blood pressure-related and beneath the damaged endothelium, risk factors. However, these efforts
hormonal influences. and finally contributes to the abnor- alone cannot be completely success-
Normal functions of endothelial mal accumulation of blood compo- ful because age itself is a major risk
cells include mediation of coagula- nents around the atherosclerotic factor for atherosclerosis.
tion, platelet adhesion, immune lesion.29 Atherosclerotic risk conferred by
function, control of volume and Fibrinogen is a clotting factor age is attributable in large measure
electrolyte content of the intravas- that accumulates at the site of the to pathological endothelial dysfunc-
cular and extravascular spaces. tion.37,38 As noted earlier, endothelial
52 MARCH 2009/UPDATE
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dysfunction is not synonymous with mute for a long time and frequently were not diagnosed with the condi-
atherosclerosis, but the two proc- manifests itself with an acute car- tion, and beta-carotene levels were
esses are increasingly intertwined diovascular event; therefore, the less than a third of those without
with advancing age. possibility of detecting the disease atherosclerosis.
in a subclinical phase and reducing Oxidative stress resulting from the
Endothelial dysfunction or reversing its progression is an oxidation of low-density lipoprotein
markers: issue of relevance,” the authors (LDL) cholesterol in the wall of the
1. VEGF (Vascular endothelial write. “Antioxidants, which may artery results in inflammation which
growth factor) inhibit lipid peroxidation, could stimulates the differentiation of im-
2. ADMA (Asymmetric dimethyl- play an important protective role mune system cells called monocytes
arginine) against the formation of simple into macrophages. Macrophages
3. VCAM-1 (vascular cell adhesion and complex atherosclerotic le- accumulate lipids to form foam
molecules) sions, which progressively protrude cells which thicken the walls of the
4. NOS (Nitric oxide synthase) into the arterial lumen, causing artery. Antioxidants such as those
ADMA is involved in the pathogen- stenosis or occlusion. In particular, evaluated in the current study could
esis of hypertension and atheroscle- increased carotid intima-media help protect against this process by
rosis through its inhibition of the thickness represents an early phase preventing LDL oxidation.
formation of the endogenous vascu- of the atherosclerotic process and is “Regular intake of foods rich in
loprotective molecule, nitric oxide widely used as a marker of subclini- lycopene and other antioxidant
(NO). Determination of ADMA can cal atherosclerosis which correlates vitamins may slow the progression
thus help to predict both the likeli- with established coronary heart of atherosclerotic processes and
hood of developing cardiovascular disease.” modify the early stages of athero-
disease and its prognosis. A new Two hundred and twenty men sclerosis, with a consequent reduc-
competitive ELISA test for ADMA is a and women between the ages of tion in cardiovascular events,” the
useful and fully validated tool suit- 45 and 65 without history of tran- authors conclude.
able for routine laboratory use. sient ischemic attack, stroke, or
Available tests to detect endothe- other conditions related to carotid Oxidative stress profile
lial dysfunction in South Africa artery disease were enrolled at the (blood)
include : San Camillo de Lellis Hospital, in 1. Malondialdehyde
a) Ultra sensitive CRP Manfredonia, Italy. Participants 2. Glutathione
b) Von Willebrand Factor (WF) underwent ultrasonographic evalu- 3. CoEnzyme Q10
c) PAI-1 (Plasminogen activator ation of the extracranial carotid 4. Vitamin C
inhibitor-1) arteries, and blood samples were 5. b-Carotene (including cryptoxan-
d) FDP (Fibrinogen degradation analysed for lipids, C-reactive pro- thin and lycopene)
products) – as D-dimer tein and other factors, in addition to
plasma levels of vitamin A, vitamin RefeRences :
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