Abstract 4399: Over-expression of Heat Shock Protein 27 Accelerates Re-endothelialization and Attenuates Neointimal Formation Post-Arterial Injury
Introduction: Novel data from this laboratory establishes that Heat Shock Protein 27 (HSP27) is atheroprotective - in part by attenuating acLDL uptake (by binding SR-A) and vascular inflammation [Circ Res 2008]. Inflammation plays less of a role in neointima formation following arterial injury yet we recently demonstrated that blood-borne cells of a mononuclear lineage are important contributors to the neointima that forms post-injury/stenting [PLoS 2008, Card Res 2009].
Objective: Hence we asked if over-expression of HSP27 (HSP27 o/e) might ameliorate experimental neointima formation in mice.
Methods/Results: 72 male and female wild type (WT) and HSP27o/e mice were fed a normal chow and subjected to femoral artery injury (passage of a blunt needle to denude the endothelium) before being euthanized 7, 14 or 28 days thereafter. Serum HSP27 levels did not change with injury. By 28 days the intima:media ratio was reduced by 52% and 75% in male and female HSP27o/e mice respectively (e.g., males: 0.34±0.06 vs. 0.71±0.14 and females: 0.14±0.05 vs. 0.57±0.06; p<0.05 for both sexes). Surprisingly, re-endothelialization (as demarcated by Evan’s blue staining) was increased by 67% and 65% in HSP27o/e males and females on day 7 relative to WT mice (e.g., males: 78.4±7.5% vs. 47.0±6.9%; females: 80.9±4.9% vs. 48.9±4.6%; p<0.05 for both sexes).
Conclusions: HSP27 over-expression reduces neointima formation post-injury and unexpectedly accelerates re-endothelialization of the injured arterial segment. These data suggest a novel role for HSP27 that extends beyond atheroprotection and may be very relevant to improving the response to stent implantation where rapid re-endothelialization is a very desirable goal. Vascular studies with recombinant HSP27 are ongoing.