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. Author manuscript; available in PMC: 2021 Aug 11.
Published in final edited form as: Circulation. 2020 May 22;142(6):575–590. doi: 10.1161/CIRCULATIONAHA.120.045981

Figure 6. Antisense long non-coding AC003075.4 is correlated with CAD in GWAS and regulates AHR expression.

Figure 6.

(a) rs6968554, a lead-SNP upstream of the AHR gene, is correlated to CAD on CARDIOGRAM+C4D (p=1e-4). (b) In GTEx vascular tissue (tibial artery), rs6968554 is an eQTL for AC003075.4 expression, a lncRNA that is anti-sense to AHR (ANOVA p=2.5e-4). (c-d) AC003075.4 and AHR expression are highly correlated (c) AC003075.4 knockdown decreases AHR expression (p = 0.0062), and (d) AC003075.4 overexpression increases AHR expression (p=0.012). (e) TCF21 positively regulates AC003075.4 expression in HCASMC (p=0.027 for overexpression, p=0.01 for knockdown). (f) We propose a working model of AHR function in the development of atherosclerosis. TCF21 is initially up-regulated and promotes SMC to dedifferentiate and participate in lesion and fibrous cap development. AHR is activated in the lesion cap and plays a role in maintaining the FMC in this region, with AHR loss promoting FMC to migrate into the neointima and assume a chondrocyte-like phenotype, i.e., transition to chondromyoctes (CMC). **P < 0.01, *P < 0.05.