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Blood Clots Are Rapidly Assembled Hemodynamic Sensors
| Content Provider | Scilit |
|---|---|
| Author | Muthard, Ryan W. Diamond, Scott L. |
| Copyright Year | 2012 |
| Description | Journal: Arteriosclerosis, thrombosis, and vascular biology Objective—: Blood clots form under flow during intravascular thrombosis or vessel leakage. Prevailing hemodynamics influence thrombus structure and may regulate contraction processes. A microfluidic device capable of flowing human blood over a side channel plugged with collagen (±tissue factor) was used to measure thrombus permeability (κ) and contraction at controlled transthrombus pressure drops. Methods and Results—: The collagen (κ$ _{collagen}$ =1.98×10$ ^{−11}$ cm$ ^{2}$ ) supported formation of a 20-µm thick platelet layer, which unexpectedly underwent massive platelet retraction on flow arrest. This contraction resulted in a 5.34-fold increase in permeability because of collagen restructuring. Without stopping flow, platelet deposits (no fibrin) had a permeability of κ$ _{platelet}$ =5.45×10$ ^{−14}$ cm$ ^{2}$ and platelet-fibrin thrombi had κ$ _{thrombus}$ =2.71×10$ ^{−14}$ cm$ ^{2}$ for ΔP=20.7 to 23.4 mm Hg, the first ever measurements for clots formed under arterial flow (1130 s$ ^{−1}$ wall shear rate). Platelet sensing of flow cessation triggered a 4.6- to 6.5-fold (n=3, P <0.05) increase in contraction rate, which was also observed in a rigid, impermeable parallel-plate microfluidic device. This triggered contraction was blocked by the myosin IIA inhibitor blebbistatin and by inhibitors of thromboxane A2 (TXA$ _{2}$ ) and ADP signaling. In addition, flow arrest triggered platelet intracellular calcium mobilization, which was blocked by TXA$ _{2}$ /ADP inhibitors. As clots become occlusive or blood pools following vessel leakage, the flow diminishes, consequently allowing full platelet retraction. Conclusion—: Flow dilution of ADP and thromboxane regulates platelet contractility with prevailing hemodynamics, a newly defined flow-sensing mechanism to regulate clot function. |
| Related Links | https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.112.300312 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586804/pdf https://www.ahajournals.org/doi/reader/10.1161/ATVBAHA.112.300312 |
| Ending Page | 2945 |
| Page Count | 8 |
| Starting Page | 2938 |
| ISSN | 10795642 |
| e-ISSN | 15244636 |
| DOI | 10.1161/atvbaha.112.300312 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Issue Number | 12 |
| Volume Number | 32 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2012-12-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Arteriosclerosis, thrombosis, and vascular biology Peripheral Vascular Disease |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cardiology and Cardiovascular Medicine |
