Chromogranins from Cell Biology to Physiology and Biomedicine

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The effects of reperfusion injury include (a) vascular and endothelial dysfunc-
tion, reduction of nitric oxide (NO) production, and consequently “no-reflow phe-
nomenon”; (b) contractile and metabolic dysfunction; (c) arrhythmias; and (d) cell
death, by apoptosis, swelling and contraction band-necrosis.
It is known that myocardial damages during reperfusion among others is due to
different agents: the production/formation of reactive oxygen species (ROS) and
reactive nitrogen species (RNS), the cellular/mitochondrial overload of Ca2+, the
activation of mitochondrial permeability transition pore (mPTP), the reduced avail-
ability of NO and to the activation of the nuclear factor kappa B (NFκB), and many
other known and unknown mechanisms (For extensive reviews see Dan Dunn et al.
2015 ; Pagliaro and Penna 2015 ; Tullio et al. 2013 ).
The production or the formation of ROS induces an oxidative stress, which may
play an important role in determining the extension of damage (Pagliaro et al. 2011 ;
Pagliaro and Penna 2015 ; Tritto and Ambrosio 2001 , 2013; Tullio et al. 2013 ). In
fact, oxidative stress is responsible of direct and indirect damages of molecular
components, e.g. oxidation of membrane components.
During myocardial ischemia, due to the occlusion of a coronary branch, the pro-
duction of ROS, in particular the superoxide anion (O 2 −), increases as a result of the
activation of various enzymatic complexes. In the event of reperfusion the produc-
tion and formation of various ROS/RNS strongly oxidize the myocardial fibers

Ischemia

Hypoxia

Decreased ATP level, Ion pump
disturbances, Ca++overload

Anaerobic glycolisis

Acidification

Reperfusion

Excessive

ROS production

Adhesion molecules, Inflammatory

mediators, MMP expression,

Leucocytes and platelets infiltration.

Vascular and Endothelial Dysfunction, Necrosis, Apoptosis, Arrhythmias, No-Reflow Phenomenon

Mithocondrial dysfunction, Lipid

peroxidation, Swelling and

rupture cell/mithocondria

Leukocyte/capillary plugging, Endothelial swelling,

Inflammation

NO/ROS interaction

Fig. 1 Flowchart depicting the main mechanisms of myocardial ischemia/reperfusion injury.
During ischemia, several mechanisms related to absence of oxygen may lead to tissues damage.
Also during the reperfusion several mechanisms can be responsible for the negative effects
observed after an ischemic insult. In particular, the reactive oxygen species (ROS) production
increases with many deleterious action at vascular and cardiac levels, including No-reflow phe-
nomenon. Of course, the final results of the processes of ischemia and reperfusion are loss of car-
diac tissues (see text for more explanation)

Cardioprotection and Chromogranin A-Derived Peptides