Abnormal Pressure Stress Reduces Interleukin-1β-Induced Cyclooxygenase-2 Expression in Cultured Rat Vascular Smooth Muscle Cells

Abstract

Elevated mechanical stress on blood vessels associated with hypertension has a direct effect on the function of vascular endothelial cells and vascular smooth muscle cells (VSMCs).In the present study, we have identified the effect of pulsatile pressure stress on cyclooxygenase-2 (COX-2) expression induced by interleukin (IL)-1β in cultured rat VSMCs. VSMCs were isolated from aortic media of Wistar rats and cultured. Pulsatile pressure applied to VSMCs was repeatedly given between either 80 and 160 mmHg, which simulates systolic hypertension, or 80 and 120 mmHg, which simulates normal blood pressure, at a frequency of 4 cycles per min using our original apparatus. Pressure loading that simulates systolic hypertension reduced IL-1β-induced COX-2 expression. The pressure also inhibited the rapid and transient phosphorylation of extracellular signal-regulated kinase (ERK) induced by IL-1β. IL-1β-induced COX-2 expression was significantly inhibited by a specific conventional protein kinase C (PKC) inhibitor. Pressure loading that simulates systolic hypertension also reduced phorbol myristate 13-acetate (PMA) (a PKC activator)-induced COX-2 expression and the rapid and transient phosphorylation of ERK. Pressure loading that simulates normal blood pressure had no effect on IL-1β-and PMA-induced COX-2 expression. The present study shows that pressure stress between 80 and 160 mmHg, which simulates systolic hypertension reduces IL-1β-induced COX-2 expression by affecting a mechanism involving PKC and ERK signaling pathways. Downregulation of COX-2 expression in VSMCs by abnormal pressure stress may further worsen local vascular injury associated with hypertension.

Pressure stress delays cyclooxygenase-2 expression induced by interleukin-1β in cultured human pulmonary artery smooth muscle cells

“…Protein expression and phosphorylation were evaluated by Western blot analysis as previously described [ 19 ]. The cells were washed with ice-cold phosphate-buffered saline, and whole cell lysates were prepared in a mammalian protein extraction buffer (GE Healthcare Life Sciences, Buckinghamshire, UK) containing a protease inhibitor mix (GE Healthcare Life Sciences).…”

“…We previously developed a pressure-loading apparatus that can apply arbitrary pressure to cultured cells [ [16] , [17] , [18] ]. Using this apparatus, we found that applying pulsatile pressure stress between 80 and 160 mmHg at a rate of 4 cycles/min in order to simulate systolic hypertension significantly suppresses IL-1β-induced COX-2 expression in rat aortic SMCs [ 19 ]. The inhibition of mitogen-activated protein kinase (MAPK) phosphorylation was involved in the mechanism for the pressure-induced suppression of COX-2 expression [ 19 ].…”

“…Using this apparatus, we found that applying pulsatile pressure stress between 80 and 160 mmHg at a rate of 4 cycles/min in order to simulate systolic hypertension significantly suppresses IL-1β-induced COX-2 expression in rat aortic SMCs [ 19 ]. The inhibition of mitogen-activated protein kinase (MAPK) phosphorylation was involved in the mechanism for the pressure-induced suppression of COX-2 expression [ 19 ]. Therefore, it is possible that pressure stress simulating PH affects COX-2 expression in PASMCs.…”

Sodium Danshensu Cream Promotes the Healing of Pressure Ulcers in Mice through the Nrf2/HO-1 and NF-κB Pathways

“…IL-1β is one of the most common proinflammatory cytokines, and as an initial factor regulating inflammation, it is considered as the most classical inflammatory regulator [39]. As a multifunctional inflammatory factor, IL-1β is crucial for fever, wound healing, inflammatory stimulation, hematopoiesis, immune response, and other physiological responses [40]. IL-6 can activate acute response proteins, play a proinflammatory role, affect the growth of fibroblasts and endothelial cells, and activate the local and systemic defense mechanisms of the host [41].…”

“…Our findings revealed that SDSS reduced the levels of IL-1β, IL-6, and TNF-α, thereby accelerating the healing of PU in mice. responses [40]. IL-6 can activate acute response proteins, play a proinflammatory role, affect the growth of fibroblasts and endothelial cells, and activate the local and systemic defense mechanisms of the host [41].…”