Expression and significance of mitogen-activated protein kinase/extracellular signal-regulated kinase pathway in vascular tissue at site of intimal hyperplasia after arteriovenous fistula and myofibroblasts in uremic sera

Objective  To explore the expression and significance of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway in vascular tissue of intimal hyperplasia after arteriovenous fistula (AVF) and explore the effect of suppressing MAPK/ERK pathway on autophagy and proliferation of myofibroblasts.

Methods  From January 2023 to March 2023, 6 patients undergoing reconstruction of AVF were selected. Vascular tissues of patients with severe intimal hyperplasia were collected in observation group while normal collateral venous tissues requiring ligation in control group. General data were collected before operation and inner diameter and intima thickness of vessels were measured by ultrasound. The vascular expression levels of phosphorylation-extracellular regulated protein kinase 1/2 (p-ERK1/2), myosin-like B cell lymphoma/leukemia-2 interacting protein 1 (Beclin-1) and proliferating cell nuclear antigen (PCNA) proteins were detected by Western blot (WB) and correlation with venous intimal thickness was examined. Myofibroblast was cultured in uremic sera and exposed to ERK1/2 inhibitor corynoxeine. Total protein and RNA of cells were extracted and the expression changes of Beclin-1 and PCNA detected by WB and real-time polymerase chain reaction (PCR).

Results  Insufficient blood flow appeared during dialysis. Gray scale ultrasound indicated that venous intima thickened obviously (0.143±0.014) cm vs (0.097±0.016) cm at the stenosis of AVF and average diameter of vascular lumen was (0.166±0.028) cm. As compared with normal collateral vascular tissues, the expressions of p-ERK1/2, Beclin-1 and PCNA proteins were markedly up-regulated in vascular tissues of severe intimal hyperplasia and the differences were statistically significant (P<0.05). In observation group, venous intimal thickness was correlated positively with the expression levels of P-ERK1/2, Beclin-1 and PCNA proteins (R² values of 0.929, 0.702 and 0.789, P<0.05). As compared with normal control group, the expressions of Beclin-1 and PCNA spiked markedly in uremic sera (P<0.05). After an addition of corynoxeine, the expressions of Beclin-1 and PCNA became obviously down-regulated (P<0.05) and the differences were statistically significant.

Conclusions  Involved in AVF intimal hyperplasia, MAPK/ERK pathway promotes cellular autophagy and proliferation. Suppressing pathway activity may arrest cellular autophagy and proliferation and alleviate endometrial hyperplasia.