Induction of BMP4 in Vascular Smooth Muscle Cells by Shear Stress

Abstract

Introduction Bone morphogenic protein-4 (BMP4) promotes inflammatory responses and vascular calcification. Smooth muscle cells proliferation and migration occur in the denuded arteries post angioplasty. We assessed whether pulsatile shear stress (PSS) vs. oscillatory shear stress (OSS) regulated BMP2 and BMP4 expression in bovine aortic endothelial cell (BAEC) and vascular smooth muscle cell (VSMC). Methods Confluent BAEC and VSMC monolayers were exposed to PSS at a mean shear stress (τave) of 23 dyn.cm−2 and a temporal gradient (∂τ/∂t) at 71 dyn.cm.−2.sec−2; and OSS at τave= 0.02 ± 3 dyn.cm−2 in a dynamic parallel plate flow system for 4 hours. BMP-mRNA was measured with real-time RT-PCR Results a) VSMC (Fig. 1): OSS significantly up-regulated BMP4 by 2.2-fold and PSS by 1.64-fold (P<0.05, n=3) in VSMC. OSS significantly down-regulated BMP2 by 0.32-fold (P < 0.05), but PSS-induced down-regulation was statistically insignificant. Control samples were under static condition. Figure 1Open in figure viewerPowerPoint Smooth Muscle cell BMP mRNA expression b) BAEC (Fig. 2): OSS up-regulated BMP2 by 2-fold, and BMP4 by 1.5-fold in BAEC. Similarly, PSS induced BMP2 and BMP4 expression by 1.6- and 1.4-fold, respectively. However, these differences were statistically insignificant. Figure 2Open in figure viewerPowerPoint Endothelial BMP mRNA expression Discussion OSS was a stronger inducer of BMP4 expression in VSMC than PSS. The findings suggest that shear stress mediated increases in BMP4 expression may contribute to inflammation in the denuded regions of stented arteries.