FIGURE 2.

Hypothesis of spotty calcification in plaque rupture. Two main ways that spotty calcifications lead to plaque rupture: inflammatory cytokines from macrophages activate osteogenic differentiation, contributing to early stages of calcification. Then, a positive feedback loop between inflammation and calcification produces spotty calcification, stimulating accelerated plaque progression, including greater inflammatory burden, a larger necrotic core, and less collagen (Aikawa et al., 2007; Kataoka et al., 2012; Pu et al., 2014, 2016a; Hsu et al., 2016). In contrast, calcification neighboring the lipid pool, especially that near the fibrous cap, may intensify failure stress and cause plaque rupture (Bluestein et al., 2008; Hoshino et al., 2009). NC, necrotic core; Th, thrombus.