Research Article: Epigenetic bystander-like effects of stroke in somatic organs

Date Published: March 31, 2012

Publisher: Impact Journals LLC

Author(s): Anna Kovalchuk, Michael Lowings, Rocio Rodriguez-Juarez, Arif Muhammad, Slava Ilnytskyy, Bryan Kolb, Olga Kovalchuk.



Clinical evidence suggests that stroke may lead to damage of somatic organs. This communication of damage is well-established in the case of exposure to genotoxic agents is termed a bystander effect. Genotoxic stress-induced bystander effects are epigenetically mediated. Here we investigated whether stroke causes epigenetic bystander-like effects in the liver, kidney and heart. We found a significant increase in the levels of H3K3 acetylation and H3K4 trimethylation, as well as a decrease in the H3K9 trimethylation in the kidney tissue of stroked rats. Furthermore, here we for the first time show changes in the gene and microRNA expression profile in the kidney tissues of stroked rats, as compared to intact control animals. Interestingly, the observed changes were somewhat similar to those reported earlier in kidney injury, inflammation, and acute renal failure. Our data explain the recent epidemiological evidence for the increased incidence of acute kidney injury post-stroke and provide an important roadmap for the future analysis of the mechanisms and cellular repercussions of the stroke-induced bystander-like effects in distal somatic organs.

Partial Text

Ischemic stroke results from the occlusion of an afferent blood vessel and the subsequent reduction of the blood and oxygen supply to the affected brain regions. It accounts for roughly 80% of all clinical strokes [1]. Overall, oxidative stress and cell death (apoptosis and necrosis) are the key molecular processes that are involved in ischemic stroke.

Animals that suffered from ischemic stroke exhibited molecular epigenetic changes in the distal kidney, as well as in heart and liver, tissues. Interestingly, the aforementioned epigenetic changes were the most pronounced in the kidney tissue. The most striking changes were seen in the levels of H3K4 methylation, H3K3 methylation, and acetylation in the kidneys of stroked animals. Additionally, we also noted intriguing gene and microRNA expression changes in the kidney tissues of stroked rats. The sensitivity of kidney tissue to the distal effects of stroke is an important novel finding.