Systemic infections cause exaggerated local inflammation in atherosclerotic coronary arteries: clues to the triggering effect of acute infections on acute coronary syndromes

Abstract

Systemic infections can trigger heart attacks. We conducted an autopsy study to investigate the pathologic effect of systemic infections on coronary artery inflammation. We studied 14 atherosclerotic patients diagnosed with an acute systemic infection. Our control group (n=13) had atherosclerosis without infection. The groups were similar in luminal stenosis and age. Coronary artery sections were stained with H&E and markers for macrophages (CD68), T cells (CD3), and dendritic cells (S100). On pathologic examination, 5 infected patients had acute myocardial infarction with thrombosis. Macrophage density in plaques and in periadventitial fat was higher in the infected group (NS). The infected patients' adventitia had significantly more macrophages (1,577 +/- 1,872 vs 265 +/- 185 per mm(2); P=0.047). The macrophage density, similar in the control group's adventitia and plaque, was significantly greater in the infected group's adventitia than in the plaque. The adventitia and periadventitial fat of the infected group had more T cells than did samples from the control group (48.4 +/- 45.0 vs 14.1 +/- 6.3 per mm(2); P=0.002). The groups exhibited similar plaque T-cell density. The infected patients' plaques, but not the adventitia and periadventitial fat, had more dendritic cells than did the controls' (3.2 +/- 2.5 vs 0.3 +/- 0.5 per mm(2); P=0.022). To our knowledge, this is the 1st report to establish a connection between acute systemic infections and significant increases in inflammatory cells in the atherosclerotic coronary arteries of human beings. This offers a new therapeutic target for preventing heart attacks in high-risk patients.

Fig. 1 Section of coronary artery from an infected patient. A) Low-power view (H&E, orig. ×4). B) CD68 staining shows a substantial presence of macrophages that heavily infiltrate the plaque, adventitia, and periadventitial fat, mostly sparing the media. C, D) Increased magnification (×10) of the respective stained sections.

Fig. 2 Section of coronary artery from a control patient. A) Low-power view (H&E, orig. ×4). B) CD68 staining shows an absence of macrophages in comparison with the Figure 1 images of the infected patient's artery. C, D) Increased magnification (orig. ×10) of the respective stained sections.

Fig. 3 Section of coronary artery from an infected patient. A) Calcified plaque with substantial neovascularization (H&E, orig. ×20). B) S100-positive dendritic cells are seen mainly around neovascularization (CD68, orig. ×20).

Fig. 4 Higher numbers of macrophages (upper graph) and dendritic cells and T cells (lower graph) were observed in different layers of the atherosclerotic coronary lesions of infected patients versus control patients.

Fig. 5 Various mechanisms by which acute infections may affect atherosclerotic plaques.