Laminar high shear stress up-regulates type IV collagen synthesis and down-regulates MMP-2 secretion in endothelium. A quantitative analysis |
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Authors: | Tetsu Yamane Masako Mitsumata Noriko Yamaguchi Tadao Nakazawa Kunio Mochizuki Tetsuo Kondo Tomonori Kawasaki Shin-ichi Murata Yoji Yoshida Ryohei Katoh |
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Affiliation: | (1) Department of Human Pathology, School of Medicine, University of Yamanashi, Yamanashi, Japan;(2) Department of Pathology, School of Medicine, Nihon University, 30-1 kamicho, Oyaguchi, Itabashi-ku Tokyo, 173-8610, Japan;(3) Department of Cell Biology and Histology, School of Medicine, Akita University, Akita, Japan;(4) Department of Intractable Neurological and Cognitive Disorders, Institute of Brain and Blood Vessels, Mihara Memorial Hospital, Gunma, Japan; |
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Abstract: | Remodeling of endothelial basement membrane is important in atherogenesis. Since little is known about the actual relationship between type IV collagen and matrix metalloprotease−2 (MMP-2) in endothelial cells (ECs) under shear stress by blood flow, we performed quantitative analysis for type IV collagen and MMP-2 in ECs under high shear stress. The mRNA of type IV collagen from ECs exposed to high shear stress (10 and 30 dyn/cm2) had a higher expression compared to ECs exposed to a static condition or low shear stress (3 dyn/cm2) (P < 0.01). 3H-proline uptake analysis and fluorography revealed a remarkable increase of type IV collagen under high shear stress (P < 0.01). In contrast, zymography revealed that exposing to high shear stress, however similar positivity was leveled in the intracellular MMP-2 in the control and high shear stress-exposed ECs, reduced the secretion of MMP-2 in ECs. The results of Northern blotting, gelatin zymography and monitoring the intracellular trafficking of GFP-labeled MMP-2 revealed that MMP-2 secretion by ECs was completely suppressed by high shear stress, but the intracellular mRNA expression, protein synthesis, and transport of MMP-2 were not affected. In conclusion, we suggest that high shear stress up-regulates type IV collagen synthesis and down-regulates MMP-2 secretion in ECs, which plays an important role in remodeling of the endothelial basement membrane and may suppress atherogenesis. |
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