Contemporary advances in high-throughput screening of biological samples have added unbiased screens to the classical candidate approach for implicating mediators in various disease states. In this issue of JACC: Basic to Translational Science, Matic et al.(1) report transcriptomic and proteomic profiling of atherosclerotic plaques banked from carotid endarterectomies. In parallel, they looked at blood sampled near the lesion in vivo in comparison to peripheral blood. The investigators found a single molecule of many tested to be overexpressed in this collection of atherosclerotic lesions that received surgical remediation compared with nonatherosclerotic arterial specimens. They identified biliverdin reductase B (BLVRB) as significantly increased at a messenger RNA, local protein, and plasma protein levels, in company with parallel rises in heme oxygenase 1 (HMOX1). BLVRB participates in catabolism of heme.