TY - JOUR
T1 - Biphasic pattern of cell turnover characterizes the progression from fatty streaks to ruptured human atherosclerotic plaques
AU - Lutgens, Esther
AU - De Muinck, Ebo D.
AU - Kitslaar, Peter J.E.H.M.
AU - Tordoir, Jan H.M.
AU - Wellens, Hein J.J.
AU - Daemen, Mat J.A.P.
PY - 1999/2/1
Y1 - 1999/2/1
N2 - Objective: To study the amount and phenotype of DNA-synthesizing and apoptotic cells during atherogenesis. Methods: Atherosclerotic lesions (n=76), obtained at autopsy (N=6) or during vascular surgery (N=8), were classified [type I-VI; American Heart Association (AHA) classification], immunolabeled with MIB 1 or the TUNEL technique and double stained with cell- type-specific antibodies. Subsequently, the labeled fractions were quantified. Results: In type II-VI lesions, intimal DNA synthesis was increased compared to that of the non-diseased (ND) arterial wall. DNA synthesis peaked in early type II lesions (2.7±0.5 vs. 0.02±0.02% in ND; p<0.05), and declined to 0.7±0.2% in type V lesions (p<0.05). Interestingly, a second peak of DNA synthesis of 1.7±0.1%, was observed in type VI (ruptured plaque) lesions. Double staining revealed that DNA synthesis was mostly confined to the macrophage-derived foam cell (51.9%). In type II lesions, 100.0% of all DNA-synthesizing cells were present in the intimal foam cell-rich area, while in advanced type III, IV and V lesions, DNA synthesis had shifted to the shoulder region (74.8, 78.5 and 68.1%, respectively). In type VI lesions, DNA synthesis was present in the area underlying the plaque rupture (52.7%). Apoptosis was only elevated in advanced type IV, V and VI lesions (0.82±0.1, 0.8±0.1 and 1.1±0.1%, respectively, vs. 0.0±0.0% in ND) and was predominant in the lipid core (90.5% in type IV lesions; 54.2% in type V lesions) or equally divided between the lipid core and the region underlying the plaque rupture (31.8 and 34.6% in type VI lesions). In type III-VI lesions, 50.0, 38.9, 42.6 and 42.8% of the TUNEL-positive cells were macrophages. Conclusions: In stable atherosclerotic lesions, DNA synthesis is an early event, while apoptosis is a late event. Ruptured plaques show a second peak of cell turnover. Lastly, cell turnover is mostly confined to the macrophage-derived foam cell.
AB - Objective: To study the amount and phenotype of DNA-synthesizing and apoptotic cells during atherogenesis. Methods: Atherosclerotic lesions (n=76), obtained at autopsy (N=6) or during vascular surgery (N=8), were classified [type I-VI; American Heart Association (AHA) classification], immunolabeled with MIB 1 or the TUNEL technique and double stained with cell- type-specific antibodies. Subsequently, the labeled fractions were quantified. Results: In type II-VI lesions, intimal DNA synthesis was increased compared to that of the non-diseased (ND) arterial wall. DNA synthesis peaked in early type II lesions (2.7±0.5 vs. 0.02±0.02% in ND; p<0.05), and declined to 0.7±0.2% in type V lesions (p<0.05). Interestingly, a second peak of DNA synthesis of 1.7±0.1%, was observed in type VI (ruptured plaque) lesions. Double staining revealed that DNA synthesis was mostly confined to the macrophage-derived foam cell (51.9%). In type II lesions, 100.0% of all DNA-synthesizing cells were present in the intimal foam cell-rich area, while in advanced type III, IV and V lesions, DNA synthesis had shifted to the shoulder region (74.8, 78.5 and 68.1%, respectively). In type VI lesions, DNA synthesis was present in the area underlying the plaque rupture (52.7%). Apoptosis was only elevated in advanced type IV, V and VI lesions (0.82±0.1, 0.8±0.1 and 1.1±0.1%, respectively, vs. 0.0±0.0% in ND) and was predominant in the lipid core (90.5% in type IV lesions; 54.2% in type V lesions) or equally divided between the lipid core and the region underlying the plaque rupture (31.8 and 34.6% in type VI lesions). In type III-VI lesions, 50.0, 38.9, 42.6 and 42.8% of the TUNEL-positive cells were macrophages. Conclusions: In stable atherosclerotic lesions, DNA synthesis is an early event, while apoptosis is a late event. Ruptured plaques show a second peak of cell turnover. Lastly, cell turnover is mostly confined to the macrophage-derived foam cell.
KW - Apoptosis
KW - Atherosclerosis
KW - Macrophage
KW - Proliferation
KW - Smooth muscle
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U2 - 10.1016/S0008-6363(98)00311-3
DO - 10.1016/S0008-6363(98)00311-3
M3 - Article
C2 - 10341847
AN - SCOPUS:0033019113
SN - 0008-6363
VL - 41
SP - 473
EP - 479
JO - Cardiovascular research
JF - Cardiovascular research
IS - 2
ER -