Accelerated cerebral vascular injury in diabetes is associated with vascular smooth muscle cell dysfunction

Individuals with diabetes are more susceptible to cerebral vascular aging. However, the underlying mechanisms are not well elucidated. The present study examined whether the myogenic response of the middle cerebral artery (MCA) is impaired in diabetic rats due to high glucose (HG)–induced cerebral v...

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Bibliographic Details
Published in:GeroScience 2020-04, Vol.42 (2), p.547-561
Main Authors: Guo, Ya, Wang, Shaoxun, Liu, Yedan, Fan, Letao, Booz, George W., Roman, Richard J., Chen, Zongbo, Fan, Fan
Format: Article
Language:English
Subjects:
Aging
Animals
Biomedical and Life Sciences
Cell Biology
Cerebral Arteries
Cerebral blood flow
Depolarization
Diabetes
Diabetes mellitus
Diabetes Mellitus, Experimental - complications
Electron transport
Geriatrics/Gerontology
Hyperglycemia
Life Sciences
Membrane fusion
Membrane potential
Mitochondria
Molecular Medicine
Muscle contraction
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - physiopathology
Original
Original Article
Perfusion
Rats
Rats, Sprague-Dawley
Rodents
Smooth muscle
Superoxide
Vascular System Injuries
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Summary:Individuals with diabetes are more susceptible to cerebral vascular aging. However, the underlying mechanisms are not well elucidated. The present study examined whether the myogenic response of the middle cerebral artery (MCA) is impaired in diabetic rats due to high glucose (HG)–induced cerebral vascular smooth muscle cell (CVSMC) dysfunction, and whether this is associated with ATP depletion and changes in mitochondrial dynamics and membrane potential. The diameters of the MCA of diabetic rats increased to 135.3 ± 11.3% when perfusion pressure was increased from 40 to 180 mmHg, while it fell to 85.1 ± 3.1% in non-diabetic controls. The production of ROS and mitochondrial-derived superoxide were enhanced in cerebral arteries of diabetic rats. Levels of mitochondrial superoxide were significantly elevated in HG-treated primary CVSMCs, which was associated with decreased ATP production, mitochondrial respiration, and membrane potential. The expression of OPA1 was reduced, and MFF was elevated in HG-treated CVSMCs in association with fragmented mitochondria. Moreover, HG-treated CVSMCs displayed lower contractile and proliferation capabilities. These results demonstrate that imbalanced mitochondrial dynamics (increased fission and decreased fusion) and membrane depolarization contribute to ATP depletion in HG-treated CVSMCs, which promotes CVSMC dysfunction and may play an essential role in exacerbating the impaired myogenic response in the cerebral circulation in diabetes and accelerating vascular aging.
ISSN:2509-2715
2509-2723
DOI:10.1007/s11357-020-00179-z