2. –The inverse correlation between
high-density lipoproteins (HDL) and
cardiovascular atherosclerotic
disease is “well known”.
–However, the underlying
mechanisms of actions for
beneficial effects of HDL remain to
be completely elucidated.
3. –Although HDL acts mainly by
reversing the cholesterol transport
and inhibiting the oxidation of low-
density lipoproteins, several lines of
evidence suggest that HDL can also
act directly in cholesterol-
independent ways including
inhibition of endothelial cell
adhesion molecule expression1
and
facilitating release of prostacyclin2
from endothelial cells.
4. –Besides being a strong independent
predictor of the occurrence of
primary coronary events, a low
plasma HDL cholesterol level is also
associated with unfavorable
prognosis in patients who have
recovered from a myocardial
infarction. 5
5. –Whether this association reflects
accelerated atherogenesis or a direct
detrimental effect of a low HDL level on
postischemic myocardial function is
unknown.
–A low HDL level adversely influences
postinfarct left ventricular function in
patients with a first myocardial infarction,
independent of the severity of coronary
atherosclerosis6.
6. –As featured in VP Watch of this
week, Calabresi et al3
investigated
the possible direct cardio protective
effect of HDL administered 10
minutes before ischemia on the
isolated rat heart which underwent
20-minute low-flow ischemia
followed by a 30-minute
reperfusion.
7. The analyzed the following parameters:
– postischemic functional recovery,
– creatine kinase release in the coronary
effluent,
– expression and content of tumor necrosis
factor-α in the myocardium and
– coronary effluent and prostaglandin release.
In addition, the effect of the recombinant
TNF- α-blocking protein etanercept on
the functional recovery was also
studied.
8. Control
This figure shows the changes in cardiac function recovery in rat hearts perfused with saline (circles),This figure shows the changes in cardiac function recovery in rat hearts perfused with saline (circles),
HDLs at 0.5 mg/ml (triangles) and 1.0 mg/ml (inverted triangles).HDLs at 0.5 mg/ml (triangles) and 1.0 mg/ml (inverted triangles).
LVDP indicates left ventricular developed pressure; CPP, coronary perfusion pressure..LVDP indicates left ventricular developed pressure; CPP, coronary perfusion pressure..
HDL showed a dose-dependent beneficialHDL showed a dose-dependent beneficial
effect on cardiac functioneffect on cardiac function
Increase in
HDL dose
9. Etanercept caused a dose-dependent improvement in functional recovery. The
lipid-free apoA-I did not reproduce the effects of HDL. Reconstituted HDL
containing apoA-I and phosphatidylcholine. However, had the same effect as
native HDL.
11. – In an accompanying editorial in Circulation Research, Dipak
Das4
discussed all the known possible scenarios that contribute to
the effect of HDL on cardio-protection from ischemia/reperfusion
injury.
12. Conclusion:
• HDL exerts multiple beneficial
effects on parameters involved
in ischemia/reperfusion
mediated cardiac injury.
• This may have major
therapeutic implications in the
near future.
13. Question:
• What could be the underlying
mechanism(s) for direct cardio-
protective effect of HDL on
myocardium?
–Anti-inflammatory?
–Anti-oxidant?
–Anti-Apoptotic?
–Cholesterol reverse transfer?
14. Question:
• Is the anti-inflammatory effect of
HDL specific to ischemia-
reperfusion injury of myocardial
cells or it can exerts similar
effects on other types of cells
and tissues as well?
15. Question:
• As far as reducing adverse
cardiovascular events, do you
think the cardio-protective effect
of HDL may turn out to be more
important than its anti-
atherosclerotic effect?
16. Question:
• Since HDL has some degree of
protective effect against stroke,
is it safe to assume that anti-
atherosclerotic effect of HDL in
coronary heart disease may be
equal to its anti-stroke effect?
