Table 1:
HSP27 Immunotherapy and the Divergent Regulation of LDLR and PCSK9 Expression
| LDLR | PCSK9 | |
| Hepatic (in vivo): rHSP25 vaccination | ||
| • mRNA | Increase in LDLR mRNA (qPCR; Fig. 4C) | No change in mRNA (Suppl. Fig. IIIA) |
| • protein | Increased protein (Western blot; Fig. 4D,4E) | No change in hepatic protein levels (Suppl. Fig. IIIB,IIIC) but reduced plasma levels in male but not female mice (Fig. 4B) |
| • transcriptional regulation | No change in upstream in upstream transcriptional factors SREBP2 & HNF1-α (Suppl. Fig. IIID, IIIE) | No change in upstream in upstream transcriptional factors SREBP2 & HNF1-α (Suppl. Fig. IIID, IIIE) |
| HepG2 Hepatocytes (in vitro): [rHSP27 + PAb] treatment | LDLR | PCSK9 |
| • mRNA | Increased mRNA (qPCR; Fig. 5B) | Minor, transient decrease in mRNA (qPCR; Suppl Fig. VA) |
| • protein | Increased protein (SILAC; Fig. 5A) | Decreased protein (SILAC; Fig. 5A) |
| • dependence on intracellular cholesterol | Increased expression is independent of intracellular cholesterol (Fig. 5C) | Decreased expression is independent of intracellular cholesterol (Fig. 5C) |
| • dependence on NF-κB activation | Decreased expression with NF-kB blockade (Fig. 6B–6D) | No change in expression with NF-kB blockade (Suppl. Fig. VF) |