Page 246 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Atherosclerosis
Atherosclerosis (Ath.; arteriosclerosis) is the ! Smoking increases the risk of dying from
cause of more than half of all deaths in the the effects of coronary heart disease 1.4 to
western industrialized nations. It is a slowly 2.4fold (even light smoking), and in heavy
progressing arterial disease in which the inti- smokers up to 3.5fold. Smoking low tar and
ma (→ A1) are thickened by fibrous deposits low nicotine cigarettes does not lower this
that gradually narrow the lumen and gradually risk, but it is significantly lowered if smoking
become the site of bleeding and thrombus for- is stopped altogether. It is not clear how smok-
mation (→ B). ing promotes Ath. Possible causes are sympa-
Fatty streaks are the earliest visible sign of thetic nervous system stimulation by nicotine,
Ath. (as early as childhood). They are subendo- displacement of O 2 in the Hb molecule by car-
thelial accumulations of large, lipid-contain- bon monoxide, increased platelet adhesive-
ing cells (foam cells; → A2). Later, fibrous
ness, and raised endothelial permeability, in-
Heart and Circulation the cause of the clinical manifestation of Ath. ! Hyperhomocysteinemia (> 14 µg/L plasma,
duced by constituents in smoke.
plaques or atheroma form (→ A3), which are
e.g., due to a lack of methylenetetrahydrofolate
These plaques consist of an accumulation of
reductase [MTFR]), increases the risk of Ath., a
monocytes, macrophages, foam cells, T lym-
phocytes, connective tissue, tissue debris, and
rise of 5 µmol/L corresponding to the risk of a
20 mg/dL increase in cholesterol concentra-
cholesterol crystals. Plaques are often infected
mation, probably in several ways (see below).
The most common site of plaques are the
abdominal aorta, coronary arteries, popliteal
In the commonly occurring thermolabile gene
7 with the bacterium Chlamydia pneumoniae. tion. Homocystein (HoCys) favors plaque for-
arteries, and the cerebral circulus arteriosus polymorphism of MTFR, folate deficiency de-
(in order of frequency). velops (→ p. 34). If the latter is removed, the
Of the important risk factors of Ath. (→ C1), HoCys level becomes normal.
five can be influenced, namely hyperlipidemia, The pathogenesis of Ath. remains unex-
hypertension, smoking, diabetes mellitus, and plained, but endothelial damage (and chlamyd-
hyperhomocysteinemia. It is not clear whether ia infection?, see above) could be the primary
chlamydia infection plays an important part in event and the reaction to it may eventually
the pathogenesis of Ath., or whether it perhaps lead to plaque formation (response to injury
even triggers its development. Risk factors that hypothesis; → C). Plaques usually develop at
cannot be influenced are age, male sex, and a sites of high mechanical stress (vessel bifurca-
genetic predisposition (→ p. 246ff.). Subordi- tion); in this way also hypertension becomes a
nate factors are overweight and a sedentary risk factor. Among the reactions are an in-
or stressful lifestyle. creased lipid uptake in the vessel wall as well
! Hyperlipidemia. Serum cholesterol levels as adhesion of monocytes and thrombocytes
higher than 265 mg/dL (6.85 mmol/L) in those (→ C2,3), helped by HoCys. The monocytes
aged 35–40 years increase the risk of coronary penetrate into the intima and are transformed
heart disease fivefold compared to values of into macrophages (→ C4). These liberate reac-
< 220 mg/dL (5.7 mmol/L). 70% of this choles- tive O 2 radicals, especially the superoxide an-
–
terol is transported in low-density lipoproteins ion ·O 2 (also helped by HoCys), which have a
(LDLs) and the development of Ath. correlates general damaging effect on endothelial cells
closely with increased LDL levels. A defect in and inactivate endothelium-formed NO on its
LDL receptors leads to very early Ath. (→ way to the endothelium and the vascular mus-
p. 246ff.). A special risk factor seems to be lipo- culature: ·NO + ·O 2 – → ·ONOO – (→ C5). This
protein(a) (= LDL that contains apolipoprotein results in the loss of NO action, namely inhi-
Apo(a)). Apo(a) resembles plasminogen and bition of platelet and monocyte adhesion to
binds to fibrin so that Apo(a) may have an an- the endothelium as well as antiproliferative
tifibrinolytic and thus thrombogenic effect. and vasodilating effects on the vascular mus-
236 (On the role of triglyceride and high-density li- culature. The latter favor spasms (→ B and
poproteins [HDL], → p. 246ff.). C7). Even in the early stages of Ath., O 2 radicals
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Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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