Abstract
Several lines of evidence suggest that, besides being a strong independent predictor of the occurrence of primary coronary events, a low plasma high density lipoprotein (HDL) cholesterol level is also associated with short- and long-term unfavorable prognosis in patients, who have recovered from a myocardial infarction, suggesting a direct detrimental effect of low HDL on post-ischemic myocardial function. Experiments performed in ex vivo and in vivo models of myocardial ischemia/reperfusion (I/R) injury have clearly shown that HDL are able to preserve cardiac function when given before ischemia or at reperfusion; the protective effects of HDL against I/R injury have been also confirmed in other tissues and organs, as brain and hind limb. HDL were shown to act on coronary endothelial cells, by limiting the increase of endothelium permeability and promoting vasodilation and neoangiogenesis, on white blood cells, by reducing their infiltration into the ischemic tissue and the release of pro-inflammatory and matrix-degrading molecules, and on cardiomyocytes, by preventing the activation of the apoptotic cascade. Synthetic HDL retains the cardioprotective activity of plasma-derived HDL and may become a useful adjunctive therapy to improve clinical outcomes in patients with acute coronary syndromes or undergoing coronary procedures.
Highlights
Experiments performed in ex vivo and in vivo models of myocardial ischemia/reperfusion (I/R) injury have clearly shown that high density lipoprotein (HDL) are able to preserve cardiac function when given before ischemia or at reperfusion; the protective effects of HDL against I/R injury have been confirmed in other tissues and organs, as brain and hind limb
A series of large population studies have revealed the existence of a strong inverse correlation between plasma levels of high density lipoprotein cholesterol (HDL-C) and the incidence of coronary heart disease; interestingly, the inverse relation is observed at all levels of low density lipoprotein cholesterol, including very low concentrations achieved in statin-treated patients (Barter et al, 2007)
By using the same ex vivo experimental protocol described above, we showed that these synthetic HDL (sHDL) are able to limit I/R injury when given before or after the ischemic insult and that the two sHDL components, apoA-I and phospholipids, are not effective when given alone (Rossoni et al, 2004)
Summary
The HDL-mediated increase of prostanoids and nitric oxide levels after I/R suggests that HDL-mediated cardioprotection is due at least in part to their role in promoting vasodilation. HDL increase hypoxia-mediated angiogenesis in coronary artery endothelial cells; HDL promote endothelial cell migration, proliferation, and tubulogenesis by acting on the post-translational regulation of the hypoxia-inducible factor1/vascular endothelial growth factor axis, with a mechanism requiring HDL interaction with the scavenger receptor SR-BI and the activation of PI3K pathway (Prosser et al, 2014; Tan et al, 2014). The pro-angiogenic effect of HDL can be mediated by their ability to promote the differentiation of peripheral blood monocytes into endothelial progenitor cells, via activation of the PI3K/Akt/NO pathway (Sumi et al, 2007)
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