Abstract
Myosin light chain kinase is a key enzyme in smooth muscle cell contraction. However, whether myosin light chain kinase plays a role in the occurrence or development of intracranial aneurysms is not clear. The present study explored the function of myosin light chain kinase in human intracranial aneurysm tissues. Five aneurysm samples and five control samples were collected, and smooth muscle cells (SMCs) were dissociated and cultured. A label-free proteomic analysis was performed to screen the differentially expressed proteins between aneurysm and control samples. The expression and function of myosin light chain kinase in aneurysms were examined. We found that 180 proteins were differentially expressed between the aneurysm and control samples, among which 88 were increased and 92 (including myosin light chain kinase) were decreased in aneurysms compared to control tissues. In a model of the inflammatory environment, contractility was weakened and apoptosis was increased in aneurysm SMCs compared to human brain SMCs (p < 0.05). The knock down of myosin light chain kinase in human brain SMCs caused effects similar to those observed in aneurysm SMCs. These results indicated that myosin light chain kinase plays an important role in maintaining smooth muscle contractility, cell survival and inflammation tolerance.
Highlights
Intracranial aneurysm (IA), as a cerebrovascular disease, has an annual incidence of approximately 1–2% and is characterized by the ballooning of the intracerebral artery with high mortality due to vascular rupture (Rinkel, 2008; Brown and Broderick, 2014)
The current treatment for IA mainly involves clipping for surgical intervention and endovascular coiling based on its Abbreviations: HBVSMC, human brain vascular smooth muscle cell; IA, intracranial aneurysm; IASMCs, intracranial aneurysm smooth muscle cells; MLCK, myosin light chain kinase; SMA, anti-SM-α actin; SMCs, smooth muscle cells; STA, superficial temporal artery
This study observed the effects of MLCK downregulation in IA samples using a label-free proteomic analysis
Summary
Intracranial aneurysm (IA), as a cerebrovascular disease, has an annual incidence of approximately 1–2% and is characterized by the ballooning of the intracerebral artery with high mortality due to vascular rupture (Rinkel, 2008; Brown and Broderick, 2014). Ongoing studies characterize the process of IA formation as hemodynamic stress, thrombus formation, extracellular matrix degradation, inflammatory responses and structural changes, including SMC phenotypic modulation and apoptosis (Frosen et al, 2012; Frosen, 2014). The current treatment for IA mainly involves clipping for surgical intervention and endovascular coiling based on its Abbreviations: HBVSMC, human brain vascular smooth muscle cell; IA, intracranial aneurysm; IASMCs, intracranial aneurysm smooth muscle cells; MLCK, myosin light chain kinase; SMA, anti-SM-α actin; SMCs, smooth muscle cells; STA, superficial temporal artery. Endothelial injury may result from the reaction and migration of SMCs to the tunica intima (Etminan and Rinkel, 2016). The dysfunction of endothelial cells and the apoptosis or phenotypic modulation of SMCs could accelerate the progression of aneurysms
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