When Heroes Fall: Reduced Expression of Heat-Resistant Obscure Proteins in Ischemic Stroke

The recently discovered family of heat-resistant obscure (Hero) proteins represents a novel class with chaperone-like activity and unique protective properties. These proteins may contribute to cellular survival in ischemic stroke (IS) conditions. Herein, we aimed to investigate the expression dynamics of six Hero genes during the acute and subacute phases of IS. Peripheral blood samples were collected from IS patients in the acute (day 1, n = 47) and subacute (day 7, n = 41) phases, along with healthy controls (n = 42). Gene expression was assessed via quantitative PCR. Statistical analysis included group comparisons, multivariate regression modelling, and correlation analysis. In the acute phase, C9orf16 (P = 0.006), C11orf58 (P = 0.00001), and SERBP1 (P = 0.006) were significantly downregulated compared to controls. By day 7, SERBP1 expression normalized, while C9orf16 (P = 0.002) and C11orf58 (P = 0.0004) remained downregulated. Multivariate regression identified C11orf58 expression as a potential biomarker of IS. Expression levels of SERBP1 and C11orf58 negatively correlated with infarct size during both the acute (R = - 0.59, P = 0.00012; R = - 0.49, P = 0.004) and subacute phases (R = - 0.54, P = 0.0024; R = - 0.44, P = 0.032). eQTL analysis showed that SERBP1 SNPs were associated with reduced expression only in controls. Our findings underscore the potential relevance of Hero proteins as biomarkers or therapeutic targets in IS, warranting further investigation into their mechanistic involvement in neuroprotection and recovery.