T lymphocyte infiltration in non-rheumatic aortic stenosis: a comparative descriptive study between tricuspid and bicuspid aortic valves.

BACKGROUND: The two most common causes of aortic stenosis are primary "degenerative" calcification of tricuspid aortic valves and secondary calcification of congenital bicuspid valves. T lymphocyte infiltration occurs in stenotic tricuspid aortic valves, indicating an inflammatory component, but it has not been shown whether it also occurs in stenotic bicuspid valves. OBJECTIVE: To compare non-rheumatic tricuspid and bicuspid stenotic aortic valves for the presence and distribution of T lymphocytes. SETTING: University hospital. PATIENTS AND DESIGN: Valve specimens were obtained from 29 patients (15 women, 14 men, mean age 69 years (range 52-81 years)), referred to the hospital for aortic valve replacement because of symptomatic aortic valve stenosis. There were 17 tricuspid valves (from 10 women and seven men, mean age 71 years) and 12 bicuspid valves (from five women and seven men, mean age 67 years). To identify mononuclear inflammatory cells, sections were stained with antibodies for CD3 (pan-T cell antigen, Dako 1:400) and then graded histologically according to the degree of T cell infiltrate. RESULTS: T lymphocyte infiltration was present in both tricuspid and bicuspid stenotic aortic valves, without any significant differences in extent or localisation. CONCLUSIONS: Stenotic bicuspid aortic valves show the same degree of T lymphocyte infiltration as degenerative tricuspid aortic valves. Inflammation needs to be considered in the pathogenesis of acquired aortic stenosis, irrespective of the primary valve anomaly.

Insulin-like growth factor-1 stimulates vascular smooth muscle cell proliferation in rat aorta in vivo.

IGF-I is a mitogen for vascular smooth muscle cells (SMC) in vitro and enhances SMC proliferation in vivo in diabetic rats. In this study, we examined the effect of IGF-I on SMC proliferation in vivo in normal rats. Recombinant human IGF-I (0.87 and 3.1 mg/kg/day), was infused via osmotic minipumps in normal rats starting 3 days before they were subjected to aortic injury with a balloon catheter. IGF-I at an infusion rate of 3.1 mg/kg/day caused a significant increase in 3H-thymidine incorporation into DNA (+53%, P < 0.01) in the rat aortic intima-media 2 days after injury and DNA content (+13%, P < 0.05) after 11 days. The elastin and collagen contents were not changed by IGF-I infusion after 11 days. Body weight increased slightly while blood glucose was not affected. At an infusion rate of 0.87 mg/kg/day, IGF-I had no significant effects. These results suggest that circulating levels of IGF-I can stimulate SMC proliferation in vivo in normal rats but only at high concentrations.