Time course and cellular characteristics of the iliac artery response to acute balloon injury. An angiographic, morphometric, and immunocytochemical analysis in the cholesterol-fed New Zealand white rabbit.

Abstract

Evaluation of the response of the arterial vessel wall to acute arterial injury in experimental models has taken on substantial importance because of an increasing interest in angioplasty treatment of human atherosclerotic lesions. In this study, the response of normal arterial vessels to acute balloon injury was studied in 45 iliac artery segments from 24 New Zealand White rabbits fed a 2% cholesterol diet. At specified time points between 1 and 41 days after the initial balloon pullback injury, the iliac arteries were analyzed by angiographic, morphometric, and immunocytochemical techniques. Angiographic measurements indicated progressive compromise of the iliac artery lumen with increasing duration of time from injury. Morphometric measurements showed that intimal area increased from 0.004±0.01 mm 2 3 days after injury to 1.15±0.30 mm 2 34-41 days after injury. Cell line-specific immunocytochemical analysis identified the macrophage as a prominent component of the earliest intimal cellular infiltrate. Smooth muscle cells appeared within the intima 7-9 days after injury. As the intima increased in area, macrophages predominated along the internal elastic lamina aspect of the intimal lesion while smooth muscle cells occupied the portion of the intima adjacent to the lumen. In summary, retrograde balloon pullback injury followed by cholesterol feeding results in progressive arterial luminal narrowing due to a progressively enlarging intimal cellular infiltrate.

MFAP4 Promotes Vascular Smooth Muscle Migration, Proliferation and Accelerates Neointima Formation

“…[26][27][28] We found that MFAP4 promoted CCL2-induced monocyte chemotaxis in an integrin α V β 3 -dependent manner. As monocytes and monocyte-derived macrophages constitute the majority of leukocytes infiltrating neointimal lesions, 29,30 our experiments suggest that reduction in leukocyte influx observed in MFAP4-deficient mice can be explained by impaired monocyte recruitment toward the injury site.…”

Inhibitory Mechanisms by Which Suramin May Attenuate Neointimal Formation After Balloon Angioplasty

“…Histologically, injury-induced neointimal lesions in these non-cholesterol-fed rabbit models resernble human fibrous coronary plaques (consisting mainly of SMCs and newly-deposited extracellular matrix) and are distinct from lesions in the cholesterol-fed rabbit model (characterized by a large number of lipid-laden macrophages) and post-transplant coronary artherïopathy which is marked with intensive lymphocyte infiltration (226,227). Results from our pilot study demonstrate that suramin significantly inhibits neointimal formation after primary injury of the rabbit iliac artery (Figure 4).…”

Effect of Cyclosporine on Arterial Balloon Injury Lesions in Cholesterol-Clamped Rabbits

“…In the transplanted artery, alloimmunity involving T lymphocytes and their consequent recruitment of macrophages seem to be of major importance 51 ; cyclosporine inhibits T lymphocytes. In the balloon-injured artery, smooth muscle cell proliferation 10,26 in response to wound healing and possibly macrophages under conditions with hypercholesterolemia 13,25,30,48 may be of more importance.…”