Most human body cells include some tiny power plants known as mitochondria that produce the vast majority of the energy cells employ on daily activities. Similar to an energetic renewable resource, these small power plants are continually parting and uniting in processes known as fission and fusion.
The balance between these processes is vital for health – more particularly, cardiovascular health. New research conducted by scientists from the Lewis Katz School of Medicine at Temple University (LKSOM) has found a new mechanism by which deviations in mitochondrial fission in endothelial cells (the cells that border the inner surface of blood vessels) facilitate inflammation and oxidative stress in the cardiovascular system.
The team of researchers demonstrates in the study how the fission-fusion balance can be settled to lower inflammation using salicylate, the main active element in typical pain-relieving drugs, such as aspirin.
“It was already known that in cardiovascular disease the function of endothelial cells and mitochondria are impacted by inflammation, but we were unsure whether there was a link between the two,” explained Satoru Eguchi, MD, Ph.D., FAHA, Professor of Physiology and Professor in the Cardiovascular Research Center, Sol Sherry Thrombosis Research Center, and Center for Metabolic Disease Research at LKSOM.
In endothelial cells, chronic inflammation makes mitochondria to become smaller and broken. This harmful process is settled by a molecule called dynamin-related protein 1 (Drp1), which usually has a helpful part in keeping the fission-fusion balance. When cells get stressed under inflammation, however, it causes fission activity, which results in mitochondrial fragmentation.
“How Drp1 acts to increase mitochondrial fragmentation when endothelial cells are inflamed has been unclear,” Dr. Eguchi explained. “But we wondered whether it might interact with nuclear factor (NF)-κB, which oversees the regulation of inflammatory processes and is involved in endothelial dysfunction.”
Dr. Eguchi and his colleagues simulated inflammatory pathways in endothelial cells, which caused mitochondrial fragmentation, and then analyzed the impacts of blocking Drp1 activity and manifestation.
These tests showed that in cells, Drp1 hindrance suppresses mitochondrial fission, NF-κB activation, as well as inflammation. Decreases in fission and inflammation were also noticed in cells after NF-κB inhibition, as well as in further studies on mice genetically altered to have less Drp1.
The scientists then came with the question as to whether the anti-inflammatory drug salicylate could also decrease mitochondrial fragmentation, and discovered that, indeed, the drug attenuated both issues thanks to its impacts on NF-κB and downstream pathways.
“Our findings suggest that salicylate may be able to maintain the balance between mitochondrial fission and fusion under inflammatory conditions,” Dr. Eguchi said. “This observation could have real clinical impact since salicylate is already used in aspirin and related pain-relievers.”
Dr. Eguchi now intends to examine the effect of aging and other elements on Drp1 and mitochondrial fission in endothelial cells.
“Mitochondrial function declines with aging, but we also know that exercise and diet influence this process. How these factors come together mechanistically to impact vascular health is not fully understood,” Dr. Eguchi explained.
The paper detailing the findings has been published on May 11th in the journal Hypertension.