Transducible recombinant small heat shock-related protein, HSP20, inhibits vasospasm and platelet aggregation

EC McLemore, DJ Tessier, CR Flynn, EJ Furnish… - Surgery, 2004 - Elsevier
EC McLemore, DJ Tessier, CR Flynn, EJ Furnish, P Komalavilas, JS Thresher, L Joshi
Surgery, 2004Elsevier
BACKGROUND: Human saphenous vein (HSV) is the autologous conduit of choice for
peripheral vascular reconstruction. Injury during harvest leads to vasospasm and a
thrombogenic endoluminal surface. A proteomic transduction approach was developed to
prevent vein graft vasospasm and thrombosis. METHODS: Recombinant HSP20 protein
linked to the TAT protein transduction domain was generated in a bacterial expression
system (TAT-HSP20). The effect of this protein on the inhibition of smooth muscle contraction …
BACKGROUND
Human saphenous vein (HSV) is the autologous conduit of choice for peripheral vascular reconstruction. Injury during harvest leads to vasospasm and a thrombogenic endoluminal surface. A proteomic transduction approach was developed to prevent vein graft vasospasm and thrombosis.
METHODS
Recombinant HSP20 protein linked to the TAT protein transduction domain was generated in a bacterial expression system (TAT-HSP20). The effect of this protein on the inhibition of smooth muscle contraction was determined using rings of rabbit aorta and HSV in a muscle bath. In addition, the effects of TAT-HSP20 on platelet aggregation were determined in vitro using human citrated whole blood.
RESULTS
Recombinant TAT-HSP20 inhibited norepinephrine-induced contraction of rabbit aortic and HSV segments. Similarly, TAT-HSP20 induced smooth muscle relaxation in HSV segments precontracted with norepinephrine. In human-citrated whole blood, platelet aggregation was significantly inhibited by TAT-HSP20 in a dose-dependent manner.
CONCLUSIONS
The results of this study demonstrate that recombinant TAT-HSP20 inhibits vascular smooth muscle contraction and platelet aggregation. This suggests that HSP20 may be an ideal effector molecule to target as a proteomic approach to enhance early vein graft patency rates by preventing acute vasospasm and thrombosis.
Elsevier