Platelet Adhesion Mediated by von Willebrand Factor at High Shear Rates Is Associated with Premature Coronary Artery Disease
, Sergey Kozlov 1, Yuliya Avtaeva 2, Ivan Melnikov 2,3, Olga Saburova 2, Konstantin Guria 2, Evgeny Matroze 2,4 and Zufar Gabbasov 2,*Round 1
Reviewer 1 Report
An educational and informative manuscript that has both clinical interest and merit. However, there are some editing issues that the authors should consider and address. The following are suggestions/comments regarding those issues. Line 18, "... beneficial outcomes in drug delivery ...". Line 27, "... and future perspective usage for the delivery ...". Line 50, "strength); and in response to ...". Line 52, "some other well-known manufactured ...". Line 58, "... called hydrophilic gels have received significant attention ...". Line 78, "and enzymes that lead to a fast ...". Lines 83 & 84, "... increases, the elongated percentage of the polymeric ...". Line 107, "... in both cases an external healing agent is used as a self-healing process [25]." Line 197, "... no covalent bonding; and therefore, the polymer ...". Lines 232 & 233, "... primarily designed for hydration to a dry wound." Lines 245 & 246, "... hydrophilic polymers which mainly contain many ...". Line 251, "... of the crosslinking, hydrogels are divided ...". Line 264, "... and are synthesized by the addition and ...". Line 270, "... classified into five types:" Line 281, "body tissues, hydrogels are of ...". Line 284, "capable of responding to external stimuli ...". Lines 290 & 291, "... external environment depends on two ...". Line 320, "... bulk polymerization in the presence of a solvent serving ...". Line 380, "... and ions is also important." Line 383, "... is characterized by a swelling property ...". Line2 384 & 385, "... the third parameter of elasticity [49,55]." Line 393, "... higher accuracy at a fine ...". Line 402, "... structural artifacts; hence, not trustworthy." Line 426, "... rheometer [60]. Figure 7 shows the commonly ...". Line 444, "... and constant temperature 37 degrees C...". Lines 474 & 475, "... The lower and critical strains are applied in a cyclic manner ...". Line 487, "... release, the developed hydrogel system showed great potential as a ...". Line 500, "... to benzene, found in many ...". Line 523, "... stress (viscosity) values are measured by ...". Line 54, "... increasing the shear rate, which are higher from ...". Line 539, "... cell quality, Pek et al. conducted ...". Lines 548 & 549, "... ones which refers to the ability to reverse ...". Lines 559 & 560, "... studies [78]. Angela et al. analyzed in vitro ...". Line 570, "... with artificial saliva, the retention in the lower ...". Lines 625 & 626, "... atmospheric oxygen, causing hypoxic stress ...". Line 651, "... methods. The following are some other examples of ...". Line 734, "... dissipating energy. On the other hand, the ...".
A well written manuscript.
Author Response
Dear reviewer,
Thank you for your valuable remarks. According to your suggestions, the manuscript was corrected and applied for editing and proofreading by the MDPI proofreading service. The revised and proofread manuscript is uploaded to the MDPI interactive review system.
Reviewer 2 Report
The paper Biomedicines 2482579 » Platelet adhesion mediated by von Willebrand factor (vWF) at high shear rates is associated with premature coronary artery disease« focuses on inhibition on platelet adhesion by anti GPIb monoclonal antibodies in a collagen-coated in vitro flow chamber. The authors found a median reduction of platelet adhesion by 77% in patients with premature coronary artery disease (CAD) in contrast to a reduction by only 30% in patients without CAD. A 1% reduction in GPIb antibody-mediated platelet adhesion increased the odds ratio of premature CAD by 3%. A reduction of platelet adhesion by 62.8% predicted premature CAD with a sensitivity of 70.2 % and specificity of 81.2%.
Plasma levels of VWF were higher in the control group 145 (99, 189)% than in patients with premature CAD 111% (85-143)%, p = 0.03, but an equal amount of monoclonal anti GPIb antibody (10 ug per sample) was used in all samples. However, VWF antigen levels did not correlate with baseline platelet adhesion values, nor with platelet adhesion values after GPIb inhibition. Most patients with CAD were on P2Y12 inhibitors which decreased the baseline platelet adhesion.
I have the following comments:
- The authors should discuss the differences in baseline platelet adhesion between the control group and the CAD group. Was it just an effect of antiplatelet treatment by P2Y12 inhibitors?
- In addition to the last paragraph of the Discussion, the authors should briefly discuss the possible reasons for higher levels of VWF antigen in the control group compared with the CAD group.
- Technical remark, Table 1. HDL and LDL are reversed.
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Author Response
Dear reviewer,
Thank you for your valuable remarks. According to your suggestions, the following changes were introduced into the manuscript:
Point 1. The authors should discuss the differences in baseline platelet adhesion between the control group and the CAD group. Was it just an effect of antiplatelet treatment by P2Y12 inhibitors?
Response 1. Lines 270-289 were introduced: “In this study, the values of baseline adhesion measurements were lower in patients with CAD than in control subjects. Treatment with aspirin alone did not affect platelet adhesion in CAD or in the control group. Unlike control subjects, most patients with CAD received a P2Y12 receptor inhibitor alone or DAPT. It was previously shown that aspirin did not decrease platelet aggregation and thrombus formation at high shear rates, possibly due to the suppression of prostacyclin (prostaglandin I2) production [6]. Prostacyclin is a potent inhibitor of platelet adhesion and aggregation, especially at high shear rates [6]. P2Y12 inhibitors downregulate the activation of platelet integrins through a different pathway and can affect thrombus formation at increased shear rates [11]. Worth mentioning is that although P2Y12 receptor inhibitors affected the absolute values of platelet adhesion in our study, they did not affect the values of the relative decrease in platelet adhesion after GPIb inhibition, i.e., the GPIb-mediated component of platelet adhesion. Unlike integrins, the GPIb receptor is a mechanosensing receptor. High shear rates, but not platelet activation, trigger the shear-stress-resistant binding of GPIb to VWF [3]. This allows us to evaluate the contribution of GPIb receptors to platelet adhesion without considering the effect of antiplatelet agents.”
Point 2. In addition to the last paragraph of the Discussion, the authors should briefly discuss the possible reasons for higher levels of VWF antigen in the control group compared with the CAD group.
Response 2. Lines 303-307 were added: “Furthermore, patients without CAD in this study had higher VWF:Ag levels. This could be due to several reasons. VWF:Ag levels can vary over a wide range in the same person at different times [20]. VWF:Ag levels depend on blood group, age, smoking, concomitant diseases, medication intake, and even physical activity [15,21,22].”
Point 3. Technical remark, Table 1. HDL and LDL are reversed.
Response 3. Corrected.
The manuscript was applied for editing and proofreading by the MDPI proofreading service.
