ApoC-III may act through mitochondrial stress–mediated inflammation.A, proteins with q ≤ 0.1 between normal medium (NM), procalcifying medium (PM), and PM + apoC-III increased in PM + apoC-III versus NM with proteins of major pathways highlighted (n = 4 donors, day 7 and day 14 data). B, proteins with q ≤ 0.1 between NM, PM, and PM + apoC-III increased in PM + apoC-III versus PM with proteins of major pathways highlighted (n = 4 donors, day 7 and day 14 data). C, ApoC-III incubation increased interleukin-6 (IL-6) mRNA expression (n = 5 independent donors, apoC-III or apoA-I incubation for 48 h). D, bone morphogenetic protein 2 (BMP-2) mRNA was highly expressed in valvular interstitial cells incubated with 100 μg/ml apoC-III (n = 5 independent donors, apoC-III or apoA-I incubation for 48 h). Data are expressed as mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, one-way ANOVA with Bonferroni multiple comparison test or Kruskal–Wallis test with Dunn's correction. E, potential role of ApoC-III in valvular calcification. ApoC-III induces mitochondrial dysfunction–driven inflammation that promotes calcification-associated processes.