Long alleles of the heme oxygenase 1 (HMOX1) promotor polymorphism associate with ulcerative carotid plaque and future tromboembolic events

We have previously carried out gene expression profiling of symptomatic CS to discover novel genes and pathways for carotid plaque vulnerability (Ijas et al., ATVB 2007;27:154-160, Saksi et al. J Mol Med 2011; 89:1015-26). We discovered that •the CD163-heme oxygenase-1 (HO1) pathway responsible for breakdown of toxic extracospuscular hemoglobin (Hb) released during e.g. intraplaque hemorrhages (Fig. 1) is upregulated in symptomatic CS. •although intraplaque hemorrhages (IPH) has been suspected to trigger plaque vulnerability, we did not find differences in IPH or iron deposits between symptomatic and asymptomatic CS. •however, CD163 and HO1 expression correlated with IPH and iron. •interestingly, symptomatic CS show stronger induction of the CD163-HO1 pathway in response to IPH and iron.