Pathologic intimal thickening in human atherosclerosis is formed by extracellular accumulation of plasma-derived lipids and dispersion of intimal smooth muscle cells

  • Kazunori Nakagawa
    Pathophysiological and Experimental Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
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  • Yutaka Nakashima
    Corresponding author. SRL Fukuoka Laboratory, 2-1-8 Naka, Onojo-shi, Fukuoka 816-0906, Japan.
    Division of Pathology, Japanese Red Cross Fukuoka Hospital, 3-1-1 Ogusu, Minami-ku, Fukuoka 815-8555, Japan

    SRL Fukuoka Laboratory, 2-1-8 Naka, Onojo-shi, Fukuoka 816-0906, Japan
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      • In humans, plasma-derived lipids continue to accumulate in the thickened intima.
      • Lipid pools of the pathologic intimal thickening (PIT) consist of the plasma-derived lipids.
      • The number of intimal smooth muscle cells (SMCs) does not change from diffuse intimal thickening (DIT) to the PIT.
      • There is no significant proliferation or death in SMCs.
      • SMCs are dispersed in the fatty streak and PIT.


      Background and aims

      Pathologic intimal thickening (PIT) is an important stage of atherosclerosis that leads to atheroma. The present study aimed to clarify the pathogenesis of PIT in humans.


      Coronary arteries were obtained from 43 autopsy subjects aged 15–49 years. Non-atherosclerotic intima and atherosclerotic intimal lesions were classified into four groups, i.e. diffuse intimal thickening, fatty infiltration, fatty streak, and PIT, and the number and density of macrophages and smooth muscle cells (SMCs) were determined. Components of the lesions and proliferative and apoptotic activities of macrophages and SMCs were investigated by immunohistochemistry and TUNEL assay.


      Extracellular lipids accumulated mildly in the fatty infiltration and fatty streak, and abundantly in the PIT to form the lipid pool. The extracellular lipids co-localized with apolipoprotein B and fibrinogen. Macrophage foam cells accumulated in the fatty streak and PIT, but no TUNEL-positive macrophages were detected in any lesion. No significant difference in the number of SMCs was found between the four groups, but the density of SMCs decreased in the fatty streak and PIT. The decrease correlated with an increase in the number of macrophages, and the accumulation of extracellular lipids in the lipid pool. Neither Ki-67-positive nor TUNEL-positive SMCs were detected in any lesion.


      In PIT in human atherosclerosis, the lipid pool is formed by infiltration and deposition of plasma-derived lipids. Intimal SMCs are dispersed in association with macrophage infiltration and lipid pool formation without undergoing significant proliferation or death.

      Graphical abstract


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