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Phenotypic Transformation of Smooth Muscle in Vasospasm after Aneurysmal Subarachnoid Hemorrhage

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Abstract

Differentiated smooth muscle cells (SMC) control vasoconstriction and vasodilation, but they can undergo transformation, proliferate, secret cytokines, and migrate into the subendotherial layer with adverse consequences. In this review, we discuss the phenotypic transformation of SMC in cerebral vasospasm after subarachnoid hemorrhage. Phenotypic transformation starts with an insult as caused by aneurysm rupture: Elevation of intracranial and blood pressure, secretion of norepinephrine, and mechanical force on an artery are factors that can cause aneurysm. The phenotypic transformation of SMC is accelerated by inflammation, thrombin, and growth factors. A wide variety of cytokines (e.g., interleukin (IL)-1β, IL-33, matrix metalloproteinases, nitric oxidase synthases, endothelins, thromboxane A2, mitogen-activated protein kinase, platelet-derived vascular growth factors, and vascular endothelial factor) all play roles in cerebral vasospasm (CVS). We summarize the correlations between various factors and the phenotypic transformation of SMC. A new target of this study is the transient receptor potential channel in CVS. Statin together with fasdil prevents phenotypic transformation of SMC in an animal model. Clazosentan prevents CVS and improves outcome in aneurysmal subarachnoid hemorrhage in a dose-dependent manner. Clinical trials of cilostazol for the prevention of phenotypic transformation of SMC have been reported, along with requisite experimental evidence. To conquer CVS in its complexity, we will ultimately need to elucidate its general, underlying mechanism.

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Acknowledgments

We thank Mark Inglin (University of Basel) for his editorial assistance. This work was supported by JSPS KAKENHI grant number 40312491 for NS.

Conflict of interest

We have no conflict of interest. This article does not contain any studies with human or animal subjects.

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  1. Department of Neurosurgery, Hirosaki University School of Medicine, 5-Zaihuchou, Hirosaki, Aomori Prefecture, 036-8562, Japan

    Norihito Shimamura & Hiroki Ohkuma

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  1. Norihito Shimamura
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Correspondence to Norihito Shimamura.

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Shimamura, N., Ohkuma, H. Phenotypic Transformation of Smooth Muscle in Vasospasm after Aneurysmal Subarachnoid Hemorrhage. Transl. Stroke Res. 5, 357–364 (2014). https://doi.org/10.1007/s12975-013-0310-1

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