Increase in Collagen Turnover But Not in Collagen Fiber Content Is Associated with Flow-Induced Arterial Remodeling

Abstract

Background: Degradation and synthesis of collagen are common features in arterial geometrical remodeling. Previous studies described an association between arterial remodeling and an increase in collagen fiber content after balloon injury. However, this does not exclude that the association between collagen content and remodeling depends on arterial injury since the association of collagen fiber content and arterial remodeling, without arterial injury, has not been investigated. The aim of the present study was to study the relation between flow-induced arterial geometrical remodeling, without arterial injury, and collagen synthesis and degradation, collagen fiber content and cell-migration-associated moesin levels. Methods and Results: In 23 New Zealand White rabbits an arteriovenous shunt (AV shunt) was created in the carotid and femoral artery to induce a structural diameter increase or a partial ligation (n = 27 rabbits) to induce a diameter decrease. In both models, arterial remodeling was accompanied by increased procollagen synthesis, reflected by increased procollagen mRNA or Hsp47 protein levels. In both models, however, no changes were detected in collagen fiber content. Active MMP-2 and moesin levels were increased after AV shunting. Conclusions: Collagen synthesis and MMP-2 activation were associated with arterial remodeling. However, a change in collagen fiber content was not observed. These results suggest that, during flow-induced geometrical arterial remodeling, increases in collagen synthesis are used for matrix collagen turnover and cell migration but not to augment collagen fiber content.