Professor Hong Ji-man’s team at Ajou University Hospital finds the cause of Moyamoya disease worsening
Moyamoya disease is a rare, intractable disease in which the arteries that supply blood to the brain gradually narrow and eventually become blocked.am. When the blood supply to the brain becomes insufficient, abnormal microscopic blood vessels grow to compensate for this. Since these blood vessels resemble the shape of smoke, it is called moyamoya disease, which means ‘morakmorak’ in Japanese.
Moyamoya disease is Genetic factors are assumed to be the main cause of the disease due to the high prevalence and family history in Asia, including Korea, Japan, and China.It has been done.
In this regard, Professor Hong Ji-man’s team (researcher Hee-seon Shin) of the Department of Neurology at Ajou University Hospital One of the causes of serious progression in moyamoya disease patients is the decrease in autophagy ability of vascular endothelial cells that interacts with the RNF213 mutant gene.He said.
The research team confirmed that in patients with moyamoya disease with the RNF213 gene mutation, the disease progresses more seriously when exposed to stressful environments such as nutritional deficiency and hypoxia.
The RNF213 protein is known to play an important role in removing unnecessary or abnormal proteins from our body. In Korea and Japan, the proportion of patients with RNF213 gene mutation is about 80%.
The research team compared 30 patients with moyamoya disease and 15 normal people. The patient group was divided into the RNF213 gene normal group (15 patients) and the mutant group (15 patients), and autophagy ability was analyzed in peripheral blood mononuclear cells.
As a result of the analysis, the endothelial cell function of the patient with the genetic modification was reduced, and autophagy was abnormally suppressed in the genetically modified cells.
In addition, normal and mutant RNF213 genes were randomly overexpressed in human umbilical vein endothelial cells, and then the cells were exposed to hypoxia and glucose deprivation for 2 hours to resemble the intracranial environment of patients with moyamoya disease.
As a result, more autophagic cysts were observed in endothelial cells of RNF213 gene mutation. Autophagy cysts are a form observed when abnormal proteins are removed from the cytoplasm of our body.
In particular, after exposure to hypoxia and glucose deficiency, inhibition of autophagy and decreased function of vascular endothelial cells were clearly observed, and more intracellular autophagic cysts were observed through transmission electron microscopy.
Additionally, the research team confirmed that the genetically modified cells recovered normal autophagy function after using an autophagy inducer. The research team Inhibition of autophagy and decline in vascular endothelial function worsens moyamoya disease by causing accumulation of abnormal proteins in cerebral blood vessels and decreased cerebral blood flow.He explained that it was assumed that he was ordered to do so.
Professor Hong Ji-man said, “It is significant that we have confirmed for the first time that environmental stress, such as hypoxia, seriously progresses the disease in RNF213 gene mutation moyamoya disease.”
Researcher Shin Hee-seon said, “By identifying the relationship between autophagy and vascular cell function in the peripheral blood cells of actual moyamoya patients, we look forward to the development and clinical application of new drugs in the future.”
Meanwhile, this study was published in the April online edition of the International Journal of Cerebral Blood Flow and Metabolism under the title ‘RNF213 gene mutation and reduced autophagy: pivotal association with endothelial dysfunction in moyamoya disease.’
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