Molecular Basis for the Anti‐inflammatory Effect of Arterial Elastic Laminae

Abstract

Elastic laminae are extracellular matrix constituents that not only contribute to the stability and elasticity of arteries, but also play a role in the regulation of arterial morphogenesis and pathogenesis. We demonstrate in this report that an important function of arterial elastic laminae is to prevent monocyte adhesion and this function is mediated by the signal-regulatory protein (SIRP) alpha and SH2 domain-containing protein tyrosine phosphatase (SHP)-1. A rat arterial reconstruction model was established with an elastic lamina-dominant matrix or collagen-dominant adventitia as a blood-contacting surface. Leukocyte transmigration through the elastic lamina matrix and adventitia were examined at day 1, 5, 10, 20, and 30. It was found that the elastic lamina matrix was resistant to leukocyte adhesion and transmigration compared with the adventitia. The density of leukocytes within the elastic lamina matrix was about 58 – 70-fold lower than that within the adventitia from 1 to 30 days. An in vitro assay confirmed the inhibitory effect of the elastic lamina matrix on monocyte adhesion. The exposure of monocytes to the elastic lamina matrix induced activation of SIRP alpha, which in turn recruited and activated SHP-1. Elastic lamina degradation peptides could also activate SIRP alpha and SHP-1. The knockdown of SIRP alpha and SHP-1 by specific siRNA reduced the inhibitory effect of elastic laminae, resulting in a significant increase in monocyte adhesion. These observations suggest that SIRP alpha and SHP-1 mediate the inhibitory effect of elastic laminae on monocyte adhesion. Furthermore, the anti-inflammatory effect renders elastic lamina a potential blood-contacting material for arterial reconstruction.