Thrombosis and Inflammation—A Dynamic Interplay and the Role of Glycosaminoglycans and Activated Protein C
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TLDR
The cytoprotective protease activated protein C (aPC) and its strong anti-inflammatory effects thereby preventing the ensuing thrombotic complications in CVD are reviewed.Abstract:
Hemostasis, thrombosis, and inflammation are tightly interconnected processes which may give rise to thrombo-inflammation, involved in infectious and non-infectious acute and chronic diseases, including cardiovascular diseases (CVD). Traditionally, due to its hemostatic role, blood coagulation is isolated from the inflammation, and its critical contribution in the progressing CVD is underrated, until the full occlusion of a critical vessel occurs. Underlying vascular injury exposes extracellular matrix to deposit platelets and inflammatory cells. Platelets being key effector cells, bridge all the three key processes (hemostasis, thrombosis, and inflammation) associated with thrombo-inflammation. Under physiological conditions, platelets remain in an inert state despite the proximity to the endothelium and other cells which are decorated with glycosaminoglycan (GAG)-rich glycocalyx (GAGs). A pathological insult to the endothelium results in an imbalanced blood coagulation system hallmarked by increased thrombin generation due to losses of anticoagulant and cytoprotective mechanisms, i.e., the endothelial GAGs enhancing antithrombin, tissue factor pathway-inhibitor (TFPI) and thrombomodulin-protein C system. Moreover, the loss of GAGs promotes the release of mediators, such as von Willebrand factor (VWF), platelet factor 4 (PF4), and P-selectin, both locally on vascular surfaces and to circulation, further enhancing the adhesion of platelets to the affected sites. Platelet-neutrophil interaction and formation of neutrophil extracellular traps foster thrombo-inflammatory mechanisms exacerbating the cardiovascular disease course. Therefore, therapies which not only target the clotting mechanisms but simultaneously or independently convey potent cytoprotective effects hemming the inflammatory mechanisms are expected to provide clinical benefits. In this regard, we review the cytoprotective protease activated protein C (aPC) and its strong anti-inflammatory effects thereby preventing the ensuing thrombotic complications in CVD. Furthermore, restoring GAG-like vasculo-protection, such as providing heparin-proteoglycan mimetics to improve regulation of platelet and coagulation activity and to suppress of endothelial perturbance and leukocyte-derived pro-inflammatory cytokines, may provide a path to alleviate thrombo-inflammatory disorders in the future. The vascular tissue-modeled heparin proteoglycan mimic, antiplatelet and anticoagulant compound (APAC), dual antiplatelet and anticoagulant, is an injury-targeting and locally acting arterial antithrombotic which downplays collagen- and thrombin-induced and complement-induced activation and protects from organ injury.read more
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References
More filters
Journal ArticleDOI
Aggregation of blood platelets by adenosine diphosphate and its reversal.
Journal ArticleDOI
Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association.
Salim S. Virani,Alvaro Alonso,Hugo J. Aparicio,Emelia J. Benjamin,Márcio Sommer Bittencourt,Clifton W. Callaway,April P. Carson,Alanna M. Chamberlain,Susan Cheng,Francesca N. Delling,Mitchell S.V. Elkind,Kelly R. Evenson,Jane F. Ferguson,Deepak K. Gupta,Sadiya S. Khan,Brett M. Kissela,Kristen L. Knutson,Chong D. Lee,Tené T. Lewis,Junxiu Liu,Matthew Shane Loop,Pamela L. Lutsey,Jun Ma,Jason Mackey,Seth S. Martin,David B. Matchar,Michael E. Mussolino,Sankar D. Navaneethan,Amanda M. Perak,Gregory A. Roth,Zainab Samad,Gary Satou,Emily B. Schroeder,Svati H. Shah,Christina M. Shay,Andrew Stokes,Lisa B. VanWagner,Nae Yuh Wang,Connie W. Tsao +38 more
TL;DR: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascul...
Journal ArticleDOI
Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides.
TL;DR: Evidence is presented that the more unstable and major component of rabbit aorta contracting substance (RCS) formed in platelets and guinea pig lung is also thromboxane A2.
Journal ArticleDOI
Extracellular DNA traps promote thrombosis
Tobias A. Fuchs,Alexander Brill,Daniel Duerschmied,Daphne Schatzberg,Marc Monestier,Daniel D. Myers,Shirley K. Wrobleski,Thomas W. Wakefield,John H. Hartwig,Denisa D. Wagner +9 more
TL;DR: It is reported that NETs provide a heretofore unrecognized scaffold and stimulus for thrombus formation and may further explain the epidemiological association of infection with thrombosis.
Journal ArticleDOI
Distinct Roles of Autophagy in the Heart During Ischemia and Reperfusion: Roles of AMP-Activated Protein Kinase and Beclin 1 in Mediating Autophagy
Yutaka Matsui,Hiromitsu Takagi,Xueping Qu,Maha Abdellatif,Hideyuki Sakoda,Tomoichiro Asano,Beth Levine,Junichi Sadoshima,Junichi Sadoshima +8 more
TL;DR: The results suggest that, in the heart, ischemia stimulates autophagy through an AMPK-dependent mechanism, whereas ischemIA/reperfusion stimulates autophile through a Beclin 1–dependent but AM PK-independent mechanism.