Transducible recombinant small heat shock-related protein, HSP20, inhibits vasospasm and platelet aggregation.
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.
McLemore
Elisabeth C
EC
Department of Surgery, Mayo Clinic, Scottsdale, Ariz, USA.
Tessier
Deron J
DJ
Flynn
C Robert
CR
Furnish
Elizabeth J
EJ
Komalavilas
Padmini
P
Thresher
Jeffrey S
JS
Joshi
Lokesh
L
Stone
William M
WM
Fowl
Richard J
RJ
Brophy
Colleen M
CM
D000818:Animals; D001011:Aorta; D001808:Blood Vessels / Q000187:drug effects*; D015696:Gene Products, tat / Q000235:genetics; D050886:HSP20 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D011994:Recombinant Proteins; D012501:Saphenous Vein; D014661:Vasoconstriction / Q000187:drug effects*
D015696:Gene Products, tat; D050886:HSP20 Heat-Shock Proteins; C494382:HSPB6 protein, human; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D010750:Phosphoproteins; D011994:Recombinant Proteins