The Role of Autophagy in Ischemic and Reperfusion Injury of the Heart
Ischemia/reperfusion (I/R) of the heart leads to increased autophagic flow. Preconditioning stimulates autophagic flow by activating the AMPK-kinase and PI3-kinase while inhibiting the mTOR kinase. The cardioprotective effect of postconditioning is associated with activation of autophagy and increased activity of NO-synthase and AMPK. I/R stimulates autophagy, and gonadectomy suppresses it. Adaptation to hypoxia has a cardioprotective effect, which is possibly associated with the activation of autophagy. It is possible that the negative effect of the fat diet on heart tolerance to I/R is associated with inhibition of autophagy. Starvation stimulates autophagy, this effect is accompanied by an increase in the tolerance of the heart to the I/R. Oxidative stress stimulates autophagy in heart during I/R. The superoxide radical generated by NADPH-oxidase acts as a trigger for autophagy, apparently due to the activation of AMPK-kinase. There is reason to believe that AMPK, GSK-3β, JNK, MEK, and ERK kinases stimulate autophagy, while mTOR, Akt and PI3-kinase inhibit autophagy in the heart during I/R. It has been established that transcription factors FoxO1, FoxO3, NF-κB, and HIF-1α enhance autophagy in heart during I/R. Transcriptional factors STAT1 and p53 inhibit autophagy in I/R conditions of the heart. miR-325, miR-145 and miR-144 simulate autophagy, and miR-30a, miR-221, miR-638 and miR-144 inhibit autophagy in the heart with I/R. The data presented indicate that H2S increases the tolerance of the heart to the action of I/R and inhibits autophagy. Hemoxygenase-1 stimulates autophagy and prevents mitochondrial damage during hypoxia/reoxygenation of cardiomyocytes. Autophagy activation during I/R can be protective and damaging depending on the experimental model. The infarction-limiting effect depends not only on how compounds affect autophagy, but also on how they affects apoptosis, necroptosis, and necrosis cardiomyocytes in the heart with I/R.