The incidence and severity of primary cardiac events are inversely related to the plasma concentration of high-density lipoproteins (HDLs). We investigated whether HDLs may exert a direct cardioprotection in buffer-perfused isolated rat hearts, which underwent a 20-minute low-flow ischemia followed by a 30-minute reperfusion. The administration of HDLs at physiological concentrations (0.5 and 1.0 mg/mL) during the 10 minutes immediately before ischemia rapidly and remarkably improved postischemic functional recovery and decreased creatine kinase release in the coronary effluent. Reconstituted HDLs containing apolipoprotein A-I (apoA-I) and phosphatidylcholine, but not lipid-free apoA-I or phosphatidylcholine liposomes, were also effective in protecting the heart from ischemia-reperfusion injury. HDLs at reperfusion were less effective than when given before ischemia. HDLs caused a dose-dependent reduction of ischemia-induced cardiac tumor necrosis factor-α (TNF-α) expression and content, which correlated with the improved functional recovery. A parallel increase of TNF-α release in the coronary effluent was observed, due to a direct binding of cardiac TNF-α to HDLs. Taken together, these findings argue for a cause-effect relationship between the HDL-mediated removal of TNF-α from the ischemic myocardium and the HDL-induced cardioprotection. Indeed, etanercept, a recombinant TNF-α-blocking protein, caused a dose-dependent improvement of postischemic functional recovery. HDLs also enhanced ischemia-induced prostaglandin release, which may contribute to the cardioprotective effect. A low plasma HDL level may expose the heart to excessive ischemia-reperfusion damage, and HDL-targeted therapies may be helpful to induce immediate or delayed myocardial protection from ischemia-reperfusion injury.
High-density lipoproteins protect isolated rat hearts from ischemia-reperfusion injury by reducing cardiac tumor necrosis factor-alpha content and enhancing prostaglandin release / L. Calabresi, G. Rossoni, M. Gomaraschi, F. Sisto, F. Berti, G. Franceschini. - In: CIRCULATION RESEARCH. - ISSN 0009-7330. - 92:3(2003), pp. 330-337.
|Titolo:||High-density lipoproteins protect isolated rat hearts from ischemia-reperfusion injury by reducing cardiac tumor necrosis factor-alpha content and enhancing prostaglandin release|
CALABRESI, LAURA (Primo)
ROSSONI, GIUSEPPE BATTISTA (Secondo)
FRANCESCHINI, GUIDO (Ultimo)
|Settore Scientifico Disciplinare:||Settore MED/07 - Microbiologia e Microbiologia Clinica|
Settore BIO/14 - Farmacologia
|Data di pubblicazione:||2003|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1161/01.RES.0000054201.60308.1A|
|Appare nelle tipologie:||01 - Articolo su periodico|