Until recently it was undisputed dogma that
high-density lipoprotein cholesterol (HDL-C) has
solely atheroprotective properties. This notion was
based on population studies and meta-analyses
showing an association of high HDL-C plasma levels
with a decreased risk for cardiovascular disease.
Recently, however, this view has been challenged,
mainly by clinical studies showing that HDL-C levels
predicted cardiovascular death only in individuals
without CAD.
HDL particles can be divided in various
sub-fractions or subpopulations depending on their
size, composition, density, charge and physiological
function. This heterogeneity is a result of the
varying contents of lipids and proteins of the
respective LDL particles in which size and density
show an inverse correlation. According to density,
HDL particles can be classified as HDL2, which are
large and less dense, and as HDL3, which are small
and dense.
The major atheroprotective effect of HDL is thought
to be associated with its function in reverse
cholesterol transport. Anti-inflammatory,
anticoagulant and antioxidative effects have also
been described.
The anti-inflammatory and antioxidant effects are
brought about by PON-1, whereas the anticoagulant
properties of HDL seem to be related to its ability
to reduce platelet activation and decrease
expression of tissue factor.
These atheroprotective effects are lost in
dysfunctional HDL.
Current knowledge on the transition from functional
to dysfunctional HDL is still fragmentary and mainly
based on in vitro findings.
However, it is generally believed that systemic
inflammation seen in pathologies such as metabolic
syndrome, diabetes, CAD and infections contribute to
the conversion of HDL-C from an antiatherogenic to a
proatherogenic molecule.
In summary, the controversy of the atheroprotective
role of HDL-C fuelled by conflicting clinical data
might be explained by the fact that the exact
function of HDL-C and thus its role in the
development of cardiovascular pathologies depends
not so much on its quantity but more on its lipid
and protein composition, with the small dense
fraction having the highest antiatherogenic
activity.
It thus seems likely that the concept of
dysfunctional HDL-C will lead to assays with greater
sensitivity and specificity and will shape future
therapies, which will not only be based on
quantitative but more so on qualitative
modifications to change or modulate functions of HDL-C.
For more information
HDL: a question of quantity or quality?
ESC Congress News 2016 - Rome, Italy, 29 Aug 2016
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