Studies on the pathogenesis of atheroarteriosclerosis induced in rabbit cardiac allografts by the synergy of graft rejection and hypercholesterolemia.

Abstract

Heterotopic cardiac allografts were placed in the necks of 48 rabbits. In rabbits that were not immunosuppressed, allografts beat as long as 12 days, while in immunosuppressed rabbits allografts beat as long as 101 days. Coronary arterial lesions in donor hearts of rabbits fed a lipid-poor diet were found in arteries of all sizes and were mainly proliferative without fatty change. In cholesterol-fed rabbits, arterial lesions were similarly distributed, but the majority of lesions in longer surviving transplants were fatty-proliferative and some bore close resemblance to chronic human coronary atheroselerosis. In contrast to findings in cardiac homotransplants, only occasional predominantly fatty lesions were induced in small intramyocardial arteries of cholesterol-fed recipients. By electron microscopy, early arterial lesions in allografts were characterized by platelet aggregates in widened junctions between endothelial cells, sloughing of endothelium without intimal thickening but with adherence of platelets to the denuded arterial wall, and platelets deep within essentially normal media. Platelets were also seen adhering to the lining cells overlying the thickened intima of more advanced arterial lesions. Results indicate that immunologic arterial injury due to allograft rejection acting in synergy with hypercholesterolemia resulting from a dietary supplement of cholesterol can lead to rapidly developing atherosclerosis. Observations of early and evolving lesions indicate that endothelial injury and platelet interaction with the arterial wall are early and continuing events and may be of primary importance in the pathogenesis of experimental graft-induced atheroarteriosclerosis. In man, similar mechanisms may be involved in the pathogenesis of graft-induced athererosclerosis and in other instances of atherosclerosis. (Am J Pathol 87:415-442, 1977).

Full text

PDF

• 415
• 416
• 417
• 418
• 419
• …
• 442
• Next

Images in this article

Figure 10
on p.439

Figure 11
on p.439

Figure 12
on p.439

Figure 13
on p.439

Figure 14
on p.439

Figure 15
on p.440

Figure 16
on p.440

Figure 17
on p.440

Figure 18
on p.440

Figure 19
on p.440

Figure 20
on p.441

Figure 21
on p.441

Figure 22 and 23
on p.441

Figure 1
on p.437

Figure 2
on p.437

Figure 3
on p.437

Figure 4
on p.437

Figure 5
on p.437

Figure 24 and 25
on p.442

Figure 26 and 27
on p.442

Figure 6
on p.438

Figure 7
on p.438

Figure 8
on p.438

Figure 9
on p.438