Cardioprotection includes all mechanisms and means that contribute to the preservation of the heart by reducing or even preventing myocardial damage. Cardioprotection encompasses several regimens that have shown to preserve function and viability of
cardiac muscle cell tissue subjected to
ischemic insult or
reoxygenation. Cardioprotection includes strategies that are implemented before an
ischemic event (
preconditioning, PC), during an ischemic event (perconditioning, PerC) and after the event and during reperfusion (postconditioning, PostC).
These strategies can be further stratified by performing the intervention locally or remotely, creating classes of conditioning known as remote
ischemic PC (RIPC), remote ischemic PostC and remost ischemic PerC.
Classical (local)
preconditioning has an early phase with an immediate onset lasting 2–3 hours that protects against
myocardial infarction. The early phase involves
post-translational modification of preexisting proteins, brought about by the activation of
G protein-coupled receptors as well as downstream
MAPK's and
PI3/Akt. These signaling events act on the
ROS-generating
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
, activate
PKCε and the Reperfusion Injury Salvage Kinase (RISK) pathway, preventing
mitochondrial permeability transition pore (MTP) opening. The late phase with an onset of 12–24 hours that lasts 3–4 days and protects against both infarction and reversible postischemic contractile dysfunction, termed
myocardial stunning
Myocardial stunning or transient post-ischemic myocardial dysfunction is a state of mechanical cardiac dysfunction that can occur in a portion of myocardium without necrosis after a brief interruption in perfusion, despite the timely restoration ...
. This phase involves the synthesis of new cardioprotective
proteins stimulated by
nitric oxide
Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...
(NO),
ROS and
adenosine
Adenosine ( symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building ...
acting on kinases such as
PKCε and
Src, which in turn activate
gene transcription and upregulation of late PC molecular players (e.g.,
antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
enzymes,
iNOS
Nitric oxide synthases () (NOSs) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule. It helps modulate vascular tone, insulin secretion, airway tone, and perista ...
).
A role for PKCε in more contemporary cardioprotection strategies including RIPC, local PostC, and remote PostC have been either demonstrated or suggested. It was shown that PKCε translocates from the
cytosolic to the particulate fraction upon RIPC induction and that the protection conferred by RIPC can be inhibited with the PKC inhibitor
chelerythrine Similarly, in models of local PostC,
phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
and activation of PKCε has been shown to be induced and PKCε inhibition attenuated the beneficial effects of these regimens. A recent study showed that blocking
Hsp90 function with
geldanamycin inhibits PostC protection and PKCε translocation.
Additional studies are required to investigate a role for PKCε in remote PostC and PerC, as this has not been conclusively demonstrated.
References
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Heart