Hypertension is a known risk factor for the development of atherosclerosis. To assess how mechanical factors contribute to this process, mouse carotid arteries were maintained in organ culture at normal (80 mm Hg) or high (150 mm Hg) intraluminal pressure for 1, 6, 12, or 24 hours. Thereafter, fluorescent human monocytic cells (U937) were injected intraluminally and allowed to adhere for 30 minutes before washout. U937 adhesion was increased in vessels kept at 150 mm Hg 12 hours (23.5±5.7 versus 9.9±2.2 cells/mm at 80 mm Hg; P<0.05) or 24 hours (26.7±5.7 versus 8.8±1.5 cells/mm; P<0.05). At 24 hours, high pressure was associated with increased mRNA expression of monocyte chemoattractant protein-1, interleukin-6, keratinocyte-derived chemokine, and vascular cell adhesion molecule-1 (6.9±2.1, 4.4±0.1, 9.8±2.8, and 2.4±0.1-fold respectively; P<0.05), as assessed by quantitative RT-PCR and corroborated by immunohistochemistry, which also revealed an increase in intracellular adhesion molecule-1 expression. Nuclear factor κB inhibition using SN50 peptide abolished the overexpression of chemokines and adhesion molecules and reduced U937 adhesion in vessels at 150 mm Hg. Moreover, treatment of vessels and cells with specific neutralizing antibodies established that monocyte chemoattractant protein-1, interleukin-6, and keratinocyte-derived chemokine released from vessels at 150 mm Hg primed the monocytes, increasing their adhesion to vascular cell adhesion molecule-1 but not intracellular adhesion molecule-1 via α4β1 integrins. The additive effect of chemokines on the adhesion of U937 cells to vascular cell adhesion molecule-1 was confirmed by in vitro assay. Finally, pressure-dependent U937 adhesion was blunted in arteries from mice overexpressing endothelial NO synthase. Hence, high intraluminal pressure induces cytokine and adhesion molecule expression via nuclear factor κB, leading to monocytic cell adhesion. These results indicate that hypertension may directly contribute to the development of atherosclerosis through nuclear factor κB induction.

Atherosclerosis, Cytokines, Hypertension, NF-κB, VCAM-1
dx.doi.org/10.1161/01.RES.0000265231.59354.2c, hdl.handle.net/1765/35512
Circulation Research
Erasmus MC: University Medical Center Rotterdam

Riou, S, Mees, B.M.E, Esposito, B, Merval, R, Vilar, J, Stengel, D, … Lehoux, S. (2007). High pressure promotes monocyte adhesion to the vascular wall. Circulation Research, 100(8), 1226–1233. doi:10.1161/01.RES.0000265231.59354.2c