Open Access

ARTICLE

Shear Stress-mediated Angiogenesis Through Id1 Relevant to Atherosclerosis

Yidan Chen^#,1, Kang Zhang^#,1, Juhui Qiu¹, Shicheng He¹, Junyang Huang², Lu Huang¹, Dongyu Jia³, Bo Ling¹, Da Sun⁴, Xiang Xie¹, Tieying Yin^*,1, Guixue Wang^*,1

1 Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400044, China.
2 College of Agronomy and Biotechnology, Southwest University, Chongqing, 400715, China.
3 Department of Biology, Georgia Southern University, Statesboro, GA 30460-8042, USA.
4 Institute of Life Sciences, Wenzhou University, Wenzhou, 325000, China.
# These authors contributed equally to this work.
* Corresponding authors, correspondence and requests for materials should be addressed to G.W. (email: wanggx@cqu.edu.cn) or T.Y. (email: illyty28@126.com)

Molecular & Cellular Biomechanics 2017, 14(2), 83-100. https://doi.org/10.3970/mcb.2017.014.081

Abstract

Abnormal shear stress in the blood vessel is an important stimulating factor for the formation of angiogenesis and vulnerable plaques. This paper intended to explore the role of shear stress-regulated Id1 in angiogenesis. First, we applied a carotid artery ring ligation to create local stenosis in ApoE^-/- mice. Then, 3D geometry of the vessel network was reconstructed based on MRI, and our analysis of computational fluid dynamics revealed that wall shear stress of the proximal region was much higher than that of the distal region. In addition, results from histological staining of the proximal region found more vulnerable-probe plaques with new capillary formation, the presence of macrophages and collagen fibers degradation. Our in vitro and in vivo experiments further indicated high shear stress can induce endothelial cell-mediated angiogenesis and high expression of Id1. Id1-overexpression promoted endothelial cells migration and angiogenesis through collagen degradation mediated by MT-MMPs. Together, our results support a biomechanical role for Id1 in angiogenesis, suggesting manipulation of the Id1 activity may offer a novel anti-angiogenic therapeutic strategy in vulnerable plaques.

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Keywords

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