Mitochondria and cardioprotection.
Major factors linking mitochondrial dysfunction with myocardial injury are analyzed along with protective mechanisms elicited by endogenous processes and pharmacological treatments. In particular, a reduced rate of ATP hydrolysis and a slight increase in ROS formation appear to represent the prevailing components of self-defense mechanisms, especially in the case of ischemic preconditioning. These protective processes are activated by signaling pathways, which converge on mitochondria activating the mitochondrial K(ATP) channels and/or inhibiting the mitochondrial permeability transition pore. These pathways can also be stimulated by pharmacological treatments. Another major goal for cardioprotection is decreasing the burst in mitochondrial ROS formation that characterizes post-ischemic reperfusion. Finally, mitochondrial targets for therapeutic intervention may include the switch of substrate being utilized, because inhibition of fatty acid oxidation is associated with cardioprotective effects.
Di Lisa
Fabio
F
Dipartimento di Chimica Biologica, Università di Padova, Viale G. Colombo 3, Padua 35121, Italy. dilisa@civ.bio.unipd.it
Canton
Marcella
M
Menabò
Roberta
R
Kaludercic
Nina
N
Bernardi
Paolo
P
D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008928:Mitochondria / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000150:complications; D017202:Myocardial Ischemia / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D009206:Myocardium; D017382:Reactive Oxygen Species
D005227:Fatty Acids; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species