Figure 176

Two Views of the Role of the Acute-Phase Response in Atherothrombosis.
In Panel A , the uptake of oxidized low-density lipoprotein(LDL) cholesterol and LDL phosphplipids provokes macrophages and smooth muscle cells within atheromatas (1) to make C-reactive protein(CRP) and to release interleukin-6 and other mediators(2), which induce the production by the liver of C-reactive protein and other acute-phase reactants(3). The acute-phase reactants may or may not contribute to atherothrombosis. Statins inhibit the synthesis of cholesterol in the liver, increasing the expression of LDL receptors and thus lowering the LDL level. In Panel B, secretion of interleukin-6 by adipose tissue or a site of smoldering infection(1) induces the hepatic production of C-reative protein and many other acute-phase reactants (2), which enter the circulation and contribute directly to atherothrombosis(3) in susceptible persons. Statins might inhibit the production of mediators at the local site(1), intraarterial inflammation(3), or possibly the hepatic synthesis of acute –phase reactants(2). The mechanisms represented in Panels A and B could occur simultaneously in the same person. Arterial infection, if it provoked local inflammation, would provide an additional stimulus to the acute-phase response (not shown )