One of the major risk factors brought about by the atherosclerotic disease
is the increase in plasmatic cholesterol and, in particular, in cholesterol
related to low-density lipoproteins (LDL). The disease, with its chronic inflammation
features, typically displays dynamic processes that, through the initial formation
(in the very early stages) of fatty streaks in the arteries, lead to the formation
of fibrolipidic plaques, that is of atheromas.
These can be almost entirely made up of connective tissue (stable plaques)
or else contain a large core made up of extracellular lipids, surrounded by
inflammatory cells (T cells and macrophages full of lipids), as well as large
amounts of cytokines, of the procoagulant tissue factor, the metalloproteinases,
the alpha tumorous necrosis factor. The presence of such factors makes such
plaques vulnerable and susceptible of complications caused by thrombi, which
may acutely occlude coronary and peripheral arteries, thus causing myocardial
infarction and cerebral ictus. The events related to atherogenesis are extremely
complex and it is worthwhile recalling the biochemical and molecular mechanisms
governing the various stages of the disease, also in order to adequately handle
them and prevent the disease itself, as well as avoiding its worst complications.
Endothelial cells play a key role in atherogenesis, in that they modulate
the vascular tone, cell proliferation, haemostasis, platelet aggregation,
thrombogenesis, monocyte adhesiveness, inflammation, immune response and the
production of free radicals. Risk factors may alter the endothelial function,
with an increased production of radicals and a reduction in the bioavailability
of nitric oxide (NO). NO is the main vasodilator and it plays an anti-platelet
role, as well as inhibiting the growth of vascular smooth muscle cells.
The endothelial dysfunction has various causes and consequences and is related
to the oxidation of the LDLs and to the activation of blood inflammatory cells
through complicated biomolecular mechanisms, which lead to vascular lesions
and to atherothrombosis. It is important to understand both the well-known
traditional risk factors and the additional, metabolic and inflammatory ones,
which are not equally known, in order to attempt to adequately handle these.
Among the latter, certain acute phase proteins, such as the C reactive protein
and the third component of the complement (C3), have a predictive value as
far as atherosclerosis complications are concerned. The Bologna school has
reported evidence as to the fact that high levels of C3 in males are independently
associated with the risk of infarction and with a number of traditional risk
factors. The development of pharmacological agents capable of modulating the
complement system may assist us in better understanding its complex functions
and represent an important area for future research.