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Vascular involvement in mitochondrial myopathy
1Division of Ultrastructural Research, National Institute of Neuroscience, Tokyo, Japan.
Abstract:
Electron microscopic examination of muscle specimens taken at biopsy in 6 patients with complex I deficiency and 1 patient with an unknown primary chemical defect who had the clinical characteristics of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) revealed striking abnormalities in blood vessels in 5. Abnormalities consisted of an increased number of enlarged mitochondria with complicated cristae in the pericytes of capillaries, endothelial cells, and smooth muscle cells of the small arteries, including terminal arterioles and precapillary sphincters, predominantly in smooth muscle cells. On statistical analysis, the number of mitochondria and the ratio of mitochondrial area to the total area of the smooth muscle cells were increased approximately tenfold (p less than 0.001). Although stroke-like episodes were not present, similar mitochondrial abnormalities in blood vessels were found in 1 patient who had the encephalomyopathic form of complex IV deficiency and in 2 patients in whom the primary chemical defects could not be clearly defined. Such abnormalities in small arteries might be responsible for the occasional occurrence of transient cerebral ischemia causing stroke-like episodes and progressive mental deterioration.
Insights
Mitochondrial myopathy patients show abnormal blood vessel mitochondria. These vascular changes may explain stroke-like episodes in mitochondrial diseases.
Area of Science:
- Neurology
- Mitochondrial Biology
- Vascular Biology
Background:
- Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a severe condition.
- The underlying causes of MELAS and similar mitochondrial disorders are not fully understood.
- Vascular involvement in MELAS is suspected but not well-characterized.
Purpose of the Study:
- To investigate blood vessel abnormalities in patients with mitochondrial myopathy.
- To determine if mitochondrial structural changes in blood vessels correlate with clinical symptoms like stroke-like episodes.
Main Methods:
- Electron microscopic examination of muscle biopsy specimens.
- Quantitative analysis of mitochondrial morphology and distribution in vascular cells.
- Statistical analysis of mitochondrial parameters in smooth muscle cells.
Main Results:
- Significant mitochondrial abnormalities were observed in the blood vessels of 5 out of 7 patients.
- Increased number and size of abnormal mitochondria were found in pericytes, endothelial cells, and smooth muscle cells.
- Smooth muscle cells showed a tenfold increase in mitochondrial number and area (p < 0.001).
- Similar vascular mitochondrial changes were seen in patients with complex IV deficiency and undefined defects.
Conclusions:
- Abnormal mitochondria in small blood vessels may contribute to the pathophysiology of mitochondrial myopathies.
- These vascular changes could be responsible for transient cerebral ischemia, leading to stroke-like episodes and cognitive decline.
- Further research into vascular mechanisms is crucial for understanding and treating mitochondrial disorders.