The Effect of Myosin Light Chain Kinase on the Occurrence and Development of Intracranial Aneurysm

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.

Comparative bioinformatics analysis between proteomes of rabbit aneurysm model and human intracranial aneurysm with label‐free quantitative proteomics

“…Among these 180 proteins, 88 were significantly up‐regulated, and 92 were down‐regulated in the IA group compared to the STA group. The results were shown in our previous studies 16,17 …”

“…The absence of MYLK is known to be associated with several diseases, including aortic dissections 35 . We previously reported that SMCs extracted from human IA showed a trend of decreased MYLK expression and decreased contractile function 17 . SMCs depend on focal adhesion sites for their attachment to the ECM, which is crucial for effective contractions 36 .…”

Green tea protects against hippocampal neuronal apoptosis in diabetic encephalopathy by inhibiting JNK/MLCK signaling

“…MLCK is an important functional protein that regulates smooth muscle contraction. Activated MLCK phosphorylates the myosin light chain and phosphorylated myosin light chain induces smooth muscle contraction (8). MLCK was the first CaM-dependent kinase to be discovered and free Ca 2+ obtained after the binding of MLCK to calmodulin activates MLCK, which in turn activates contractile proteins (39).…”

“…Myosin light chain kinase (MLCK), a key molecule in the calcium signaling pathway (8), is expressed in hippocampal neurons, where it can accelerate the mobilization of synaptic vesicles, promote the release of various neurotransmitters and regulate the elongation of growth cones (9,10). A previous study found that the increase in nerve cell apoptosis observed in a rat model of ischemia-reperfusion brain injury might be associated with upregulation of MLCK expression and that the addition of a specific MLCK inhibitor (ML-7) significantly reduces neuronal apoptosis (11).…”

Avaliação das taxas de oclusão de aneurismas intracranianos tratados com dispositivo redirecionador de fluxo - a interferência dos ramos que se originam do interior do aneurisma

“…A parede do aneurisma pode demonstrar um gradiente espacial, com mudanças degenerativas importantes em direção ao domo do aneurisma. 42,44,45,49,50 Um estudo de 1999 comparou a parede arterial de aneurismas rotos e não rotos. 42 Os autores mostraram que aneurismas não rotos tendem a ter um endotélio intacto assim como as camadas da camada muscular lisa, com poucos macrófagos e outras células inflamatórias na parede arterial.…”