Ca2+ Oscillation in Vascular Smooth Muscle Cells Control Myogenic Spontaneous Vasomotion and Counteract Post-ischemic No-reflow

Li, J.; Zhang, Y.; Zhang, D.; Wang, W.; Xie, H.; Ruan, J.; Jin, Y.; Li, T.; Li, X.; Zhao, B.; Zhang, X.; Lin, J.; Shi, H.; Jia, J.-M.

doi:10.1101/2023.12.17.572091

bioRxiv · 10.1101/2023.12.17.572091

Ca2+ Oscillation in Vascular Smooth Muscle Cells Control Myogenic Spontaneous Vasomotion and Counteract Post-ischemic No-reflow

Li, J.·Zhang, Y.·Zhang, D.·Wang, W.·Xie, H.·Ruan, J.·Jin, Y.·Li, T.·Li, X.·Zhao, B.·Zhang, X.·Lin, J.·Shi, H.·Jia, J.-M.

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Abstract

Ischemic stroke produces the highest adult disability. Despite successful recanalization, no-reflow, or the futile restoration of the cerebral perfusion after ischemia, is a major cause of brain lesion expansion. However, the vascular mechanism underlying this hypoperfusion is largely unknown, and no approach is available to actively promote optimal reperfusion to treat no-reflow. Here, by combining two-photon laser scanning microscopy (2PLSM) and a mouse middle cerebral arteriolar occlusion (MCAO) model, we found myogenic vasomotion deficits correlated with post-ischemic cerebral circulation interruptions and no-reflow. Transient occlusion-induced transient loss of mitochondrial membrane potential ({Delta}{Psi}m) permanently impaired mitochondria-endoplasmic reticulum (ER) contacts and abolished Ca2+ oscillation in smooth muscle cells (SMCs), the driving force of myogenic spontaneous vasomotion. Furthermore, tethering mitochondria and ER by specific overexpression of ME-Linker in SMCs restored cytosolic Ca2+ homeostasis, remotivated myogenic spontaneous vasomotion, achieved optimal reperfusion, and ameliorated neurological injury. Collectively, the maintaining of arteriolar myogenic vasomotion and mitochondria-ER contacts in SMCs, are of critical importance in preventing post-ischemic no-reflow.

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Li, J., Zhang, Y., Zhang, D., Wang, W., Xie, H., Ruan, J., Jin, Y., Li, T., Li, X., Zhao, B., Zhang, X., Lin, J., Shi, H., Jia, J.-M.. 2023-12-18. Ca2+ Oscillation in Vascular Smooth Muscle Cells Control Myogenic Spontaneous Vasomotion and Counteract Post-ischemic No-reflow. https://doi.org/10.1101/2023.12.17.572091

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