Protein stabilizing factors
Compositions and methods are described for preventing or reducing protein loss due to protein aggregation, denaturation, and absorption to surfaces. Also described are compositions and methods for preventing or reducing the fouling or clogging of medical devices that come into contact with blood, such as catheters. Also described are methods to treat diseases caused by activation of the microvasculature.
1. A composition comprising:
an in vitro protein selected from the group consisting of Von Willebrand Factor (VWF), Factor VIII, ADAMTS13, and Factor IX;
an amount of (i) Apolipoprotein A1 (ApoA-1), (ii) high density lipoprotein (HDL), or (iii) ApoA-1 and HDL, sufficient to reduce or prevent loss of the in vitro protein by adsorption of the in vitro protein to an in vitro surface or by self-association; and
a transport fluid or a flush solution, wherein the transport fluid or the flush solution comprises a 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer or ethylenediamine tetraacetic acid (EDTA).
2. The composition of claim 1 , wherein the in vitro protein is a recombinant purified protein.
3. The composition of claim 1 , wherein the in vitro protein is non-recombinant.
4. The composition of claim 1 , wherein the in vitro protein is a human protein.
5. The composition of claim 1 , wherein the in vitro protein is VWF.
6. The composition of claim 5 , wherein the VWF is a VWF fragment corresponding to a processed VWF fragment selected from the group consisting of: a proteolytically cleaved VWF fragment, a furin processed VWF fragment, an ADAMTS13 processed VWF fragment, and a thrombospondin-1 processed VWF fragment.
7. The composition of claim 5 , wherein the VWF is a VWF fragment corresponding to a A1A2A3 region of VWF.
8. The composition of claim 1 , wherein the in vitro protein is Factor VIII.
9. The composition of claim 1 , wherein the in vitro protein is ADAMSTS13.
10. The composition of claim 1 , wherein the in vitro protein is Factor IX.
11. The composition of claim 1 , wherein the concentration of ApoA-1, if present, is at least 40 μg/mL, and the concentration of HDL, if present, is at least 80 μg/mL.
12. The composition of claim 1 , wherein the composition comprises ApoA-1 but not HDL.
13. The composition of claim 1 , wherein the amount of ApoA-1, HDL, or ApoA-1 and HDL is in a coating on a glass or plastic in vitro surface.
14. The composition of claim 1 , wherein the amount of ApoA-1, HDL, or ApoA-1 and HDL is in a coating on an in vitro medical device surface.
15. The composition of claim 14 , wherein the in vitro medical device surface is a surface of an in vitro catheter, port, or ventricular assist device.
16. The composition of claim 1 , wherein the amount of ApoA-1, HDL, or ApoA-1 and HDL is in a coating on an interior surface of a container holding the composition.
17. The composition of claim 1 , wherein the amount of ApoA-1, HDL, or ApoA-1 and HDL is in a coating on an in vitro synthetic microvessel surface.
18. The composition of claim 1 , wherein the amount of ApoA-1, HDL, or ApoA-1 and HDL is sufficient to reduce or prevent loss of the in vitro protein by adsorption of the in vitro protein to the in vitro surface.
19. The composition of claim 1 , wherein the amount of ApoA-1, HDL, or ApoA-1 and HDL is sufficient to reduce or prevent loss of the in vitro protein by self-association.