Antithrombotic Activity Research Articles

Comparative bioactivity profile of phospholipids from three marine byproducts based on the zebrafish model.

Phospholipids (PLs) are important components of physiological metabolism in animals and plants, and they have been widely used in clinical treatment, cosmetics, and industry. With the development of marine resources, marine PLs rich in polyunsaturated fatty acids have attracted increasing attention. As important marine resources, shrimp heads (SH), codfish roe (CR), and squid gonads (SG) contain a high PL content. The antithrombotic, antistroke, anti-inflammatory, pro-angiogenic, and cardioprotective activities of PLs from SH, CR, and SG were evaluated and compared using the in vivo zebrafish model. The results showed that the PL extracts of SH, CR, and SG had significant biological activities, which lays a theoretical foundation for the development and utilization of PLs in marine byproducts in the future, providing a new choice for the prevention of inflammatory and cardiovascular diseases. PRACTICAL APPLICATIONS: In this experiment, phospholipids in seafood from different sources were extracted, and their biological activities were comprehensively evaluated and compared using the zebrafish model to lay a foundation for the development of cardiovascular drugs, health food, special medicinal food, and other effective components. The utilization of marine byproducts not only makes full use of resources, but it also protects the environment.

Synthesis, characterization, antibacterial, antifungal and antithrombotic activity studies of new chiral selenated Schiff bases and their Pd complexes

Two new chiral selenated Schiff bases have been synthesized on condensation of a chiral selenated amine, (R)-2-(benzylselanyl)-1-phenylethanamine with 3,5-di-tert-butyl-2-hydroxy benzaldehyde ((R)-L1H) and 2-hydroxy-3-methoxybenzaldehyde ((R)-L2H), respectively. Reactions of ligands (R)-L1H and (R)-L2H with Na2[PdCl4] yielded the corresponding palladium complexes [PdCl((R)-L1–2)] ((R)-1 and (R)-2), respectively. The new ligands and complexes were characterized by 1H, 13C{1H} NMR, FT-IR spectroscopy and elemental analyses. The molecular structures of ligand (R)-L1H and its Pd complex (R)-1 were determined by single crystal X-ray diffraction. These selenated Schiff base ligands and their palladium complexes have been screened for dose-dependant antimicrobial and antithrombotic activities. Among these compounds, the ligand (R)-L2H and its Pd complex (R)-2 which are derived from ortho-vanillin showed higher antimicrobial and antithrombotic activities.

Influence of Steric Shield on Biocompatibility and Antithrombotic Activity of Dendritic Polyphosphate Inhibitor.

The polyanion, inorganic polyphosphate (polyP), is a procoagulant molecule which has become a promising therapeutic target in the development of antithrombotics. Neutralizing polyP's prothrombotic activity using polycationic inhibitors is one of the viable strategies to design new polyP inhibitors. However, in this approach, a fine balance between the electrostatic interaction of polyP and the inhibitor is needed. Any unprotected polycations are known to interact with negatively charged blood components, potentially resulting in platelet activation, cellular toxicity, and bleeding. Thus, designing potent polycationic polyP inhibitors with good biocompatibility is a major challenge. Building on our previous research on universal heparin reversal agent (UHRA), we report polyP inhibitors with a modified steric shield design. The molecular weight, number of cationic binding groups, and the length of the polyethylene glycol (PEG) chains were varied to arrive at the desired inhibitor. We studied two different PEG lengths (mPEG-750 versus mPEG-350) on the polyglycerol scaffold and investigated their influence on biocompatibility and polyP neutralization activity. The polyP inhibitor with mPEG-750 brush layer, mPEG750 UHRA-10, showed superior biocompatibility compared to its mPEG-350 analogs by a number of measured parameters without losing its neutralization activity. An increase in cationic binding groups (25 groups in mPEG750 UHRA-8 and 32 in mPEG750 UHRA-10 [HC]) did not alter the neutralization activity, which suggested that the mPEG-750 shield layer provides significant protection of cationic binding groups and thus helps to minimize unwanted nonspecific interactions. Furthermore, these modified polyP inhibitors are highly biocompatible compared to conventional polycations that have been previously used as polyP inhibitors (e.g., PAMAM dendrimers and polyethylenimine). Through this study, we demonstrated the importance of the design of steric shield toward highly biocompatible polyP inhibitors. This approach can be exploited in the design of highly biocompatible macromolecular inhibitors.

Can the treatment of polycystic ovary syndrome with spironolactone prevent severe COVID infection?

In a recent paper, Subramanian and collaborators reported a 52% increased risk of COVID-19 infection in women with polycystic ovary syndrome (PCOS) and an incidence nearly twice that of women without PCOS. The authors focused, as important factors of the increased prevalence of infection, both the inflammatory characteristic of PCOS and the increase in androgens that facilitate the entry of the virus into the cells of the target organs. We asked 200 consecutive, unvaccinated women with PCOS who had been followed with spironolactone for more than 4 months, about COVID-19 infection and found only four patients who were infected. None of the infected patients were hospitalized and only one had fever and other manifestations of the syndrome, but these symptoms resolved in a few days. The other three reported only mild or minimal symptoms. This observation needs confirmation with specific studies, considering the possibility that many other patients may have been infected by being asymptomatic and not swabbing for COVID-19. Spironolactone can increase the circulating angiotensin-converting enzyme 2 and antagonize the androgen receptor, preventing activation of transmembrane protease serine 2 in cells of the respiratory tract and other tissues. Drug also has potent anti-inflammatory and antithrombotic actions by antagonizing the mineralocorticoid receptor in target tissues and inflammatory cells. From Subramanian's study and reported observations, a proper evaluation of the use of spironolactone in COVID-19 in both PCOS and the general population is urged.

Characterization of molecular basis of anti‐platelet effect of daphnetin

Coumarin derivates have been known for their antithrombotic, anti‐inflammatory, and antioxidant activities and daphnetin is one of the natural coumarin derivatives isolated from Daphne Korean Nakai. Although the pharmacological value of daphnetin is well documented in diverse biological activities, its antithrombotic effect is not studied till date.We investigated the functional role of daphnetin and its molecular basis on the regulation of platelet activation using murine platelets.In order to check the effect of daphnetin on GPVI‐mediated platelet response, we first measured the effect of daphnetin on collagen‐induced platelet aggregation and secretion. Collagen‐induced platelet aggregation and dense granule secretion were partially inhibited in the presence of daphnetin. Interestingly, 2‐MeSADP‐induced secondary wave of aggregation and secretion were completely inhibited in the presence of daphnetin. It has been known that 2‐MeSADP‐induced secretion and the resultant secondary wave of aggregation are mediated by positive‐feedback effect of thromboxane A2 (TxA2) generation, suggesting the important role of daphnetin on TxA2 generation in platelets. Consistently, daphnetin did not affect the 2‐MeSADP‐induced platelet aggregation in aspirin‐treated platelets where the contribution of TxA2 generation is blocked. Additionally, AYPGKF‐induced platelet aggregation and secretion were inhibited in the presence of daphnetin by blocking the positive‐feedback effect of TxA2 generation. Moreover, 2‐MeSADP‐induced TxA2 generation was completely inhibited in the presence of daphnetin confirming the role of daphnetin on TxA2 generation. Finally, 2‐MeSADP‐induced ERK phosphorylation was inhibited in the presence of daphnetin.We conclude that daphnetin plays a role in platelet function by inhibiting the TxA2 generation through the regulation of ERK phosphorylation.

Formulation of Isopropyl Isothiocyanate Loaded Nano Vesicles Delivery Systems: In Vitro Characterization and In Vivo Assessment.

Isopropyl Isothiocyanate (IPI) is a poorly water-soluble drug used in different biological activities. So, the present work was designed to prepare and evaluate IPI loaded vesicles and evaluated for vesicle size, polydispersity index (PDI) and zeta potential, encapsulation efficiency, drug release, and drug permeation. The selected formulation was coated with chitosan and further assessed for the anti-platelet and anti-thrombotic activity. The prepared IPI vesicles (F3) exhibited a vesicle size of 298 nm ± 5.1, the zeta potential of −18.7 mV, encapsulation efficiency of 86.2 ± 5.3% and PDI of 0.33. The chitosan-coated IPI vesicles (F3C) exhibited an increased size of 379 ± 4.5 nm, a positive zeta potential of 23.5 ± 2.8 mV and encapsulation efficiency of 77.3 ± 4.1%. IPI chitosan vesicle (F3C) showed enhanced mucoadhesive property (2.7 folds) and intestinal permeation (~1.8-fold) higher than IPI vesicles (F3). There was a significant (p < 0.05) enhancement in size, muco-adhesion, and permeation flux achieved after coating with chitosan. The IPI chitosan vesicle (F3C) demonstrated an enhanced bleeding time of 525.33 ± 12.43 s, anti-thrombin activity of 59.72 ± 4.21, and inhibition of platelet aggregation 68.64 ± 3.99%, and anti-platelet activity of 99.47%. The results of the study suggest that IPI chitosan vesicles showed promising in vitro results, as well as improved anti-platelet and anti-thrombotic activity compared to pure IPI and IPI vesicles.

High-density lipoprotein: Quality is more important than quantity!

High density lipoproteins (HDLs) are complex lipid carriers which replace their own structures and functions according to different conditions including healthy or pathological status. HDL has substantial roles in reverse cholesterol transport system for regulation of lipid metabolism. Also HDL has many functions such as antiinflammation, antioxidation, antithrombotic and vasodilator actions. However, these functions may be compromised under pathological conditions. Nowadays, it’s known that the function of HDL is more important than it’s dose for preventing against cardiovascular diseases. This review mostly summarizes available information of HDL structure, metabolism and the real information related to the physicochemical changes of HDLs causing their different functions. Also HDLs, that lost their protective functions have been associated with oxidative stress and systemic inflammation diseases.

Physicochemical Characterization of Fucoidans from Sargassum henslowianum C.Agardh and Their Antithrombotic Activity In Vitro.

Sargassum fucoidan is a kind of sulfated heteropolysaccharide with a variety of biological activities. The aim of this study was to investigate the extraction, purification, physicochemical characterization and in vitro antithrombotic activity of fucoidan from Sargassum henslowianum C.Agardh. Hot-water-assisted ultrasound was used to extract fucoidan (F). Fucoidan was purified by DEAE cellulose 52 (F1), Vc-H2O2 (FD1) and Superdex 75 gel (FDS1). The physical and chemical properties of fucoidans were analyzed by chemical composition, monosaccharide composition, average molecular weight (Mw) and FTIR. The sulfate contents of F, F1, FD1 and FDS1 were 11.45%, 16.35% and 17.52%, 9.66%, respectively; the Mw was 5.677 × 105, 4.393 × 105, 2.176 × 104 and 6.166 × 103, respectively. The results of monosaccharide composition showed that the four fucoidans contained l-fucose, d-galactose, l-mannose, d-xylose, l-rhamnose and d-glucose, but the mass fraction ratio was different. The results of FTIR showed that fucoidan contained characteristic peaks of sugar and sulfate. In vitro, F1, FD1 and FDS1 could alleviate HUVEC damage induced by adrenaline (Adr). F1, FD1 and FDS1 decreased vWF and TF and increased the ratio of t-PA/PAI-1 in Adr-induced HUVEC.

Essential Oil Chemotypes of Four Vietnamese Curcuma Species Cultivated in North Alabama

Curcuma (turmeric) species are important culinary and medicinal plants, and the essential oils of Curcuma rhizomes have demonstrated promising pharmacological properties. The essential oils (EOs) of Curcuma species possess a wide variety of pharmacological properties, including anti-inflammatory, anticancerous, antiproliferative, hypocholesterolemic, antidiabetic, antirheumatic, hypotensive, antioxidant, antimicrobial, antiviral, antithrombotic, antityrosinase, and cyclooxygenase-1 (COX-1) inhibitory activities, among others. Curcuma oils are also known to enhance immune function, promote blood circulation, accelerate toxin elimination, and stimulate digestion. C. longa (turmeric) and C. zedoaria (zedoary) are the most extensively studied species of Curcuma due to their high commercial value. There is some interest in expanding the cultivation of Curcuma species to the southern regions in North America where the climate is favorable. The purpose of this work was to examine the rhizome essential oil composition of four species of Curcuma (C. aromatica, C. caesia, C. longa, C. zanthorrhiza) that were obtained from Vietnam and cultivated in North Alabama. The rhizome essential oils were obtained by hydrodistillation and analyzed by gas chromatographic techniques. The essential oils of C. aromatica were dominated by curzerenone (14.7–18.6%), germacrone (10.7–14.7%), 1,8-cineole (5.2–11.7%), and an unidentified component (8.7–11.0%). The major components in C. longa rhizome oil were ar-turmerone (8.3–36.1%), α-turmerone (12.7–15.2%), β-turmerone (5.0–15.4%), α-zingiberene (4.6–13.9%), and β-sesquiphellandrene (4.6–10.0%). The essential oils of C. caesia and C. zanthorrhiza were rich in curzerenone, curdione, and germacrone. These adapted turmeric varieties in North Alabama have potential use for medical purposes and medicinal plant oil market demands in the U.S.

Bioactive peptides and antinutrients in chickpea: description and properties (a review)

Legumes are a rich source of many different biologically active substances, such as fiber, proteins, vitamins and minerals. Chickpea (Cicer arietinum L.) is the third most important leguminous plant in the world: it has high nutritional value and is a source of a wide range of bioactive compounds. Bioactive peptides of chickpea seeds have antioxidant, ACE-inhibiting, cholesterollowering, antihypertensive, antimicrobial, antithrombotic, immunomodulatory, and opioid activities as well as the ability to bind minerals. But despite the benefits and high nutritional value, chickpea seeds contain antinutrients that reduce their nutritional and biological advantages. These antinutritional factors include condensed tannins, raffinose, and phytic acid. Research has shown that cooking, pregermination or fermentation can effectively reduce the indigestible content of chickpea seeds. For this purpose, it is recommended to use certain physical, chemical or biological methods: heat treatment, soaking and/or germination, enzymatic hydrolysis, irradiation, etc.This review article presents the world’s results of research aimed at studying bioactive chickpea peptides derived from chickpea seeds and ways of their formation as well as methods for elimination of antinutritional factors.

Polysaccharide-derivative coated intravascular catheters with superior multifunctional performance via simple and biocompatible method

• An intravascular catheter was coated with CMC layer exhibiting antimicrobial, antithrombotic, and low friction properties. • Whole manufacturing process was water-based, hence eco-friendly and biocompatible. • Functionalities of CMC layer were enhanced by engineering the porous structure. • Sufficient lubricity of porous CMC coated catheter was verified via trackability test. Antimicrobial, antithrombotic activity and low-friction functions are essential for the surface of intravascular catheters (ICs). However, the multifunctional surface, encompassing all of the above properties has not yet been realized. Here, we report a novel strategy for biocompatible and eco-friendly surface modification of the ICs with multifunctional polysaccharide, O-carboxymethyl chitosan (CMC). Micro- and nanoscale porous CMC (p-CMC) layer was simply fabricated via a selective elimination of the water-soluble polyethylene glycol (PEG) from heterogeneous CMC/PEG composite. The p-CMC structure exhibited a significantly enhanced hydration rate and superhydrophilic property. In particular, the antifouling property of superhydrophilic surface showed excellent anti-adhesion of Escherichia coli and platelets along with the intrinsic multifunctionality of CMC, indicating a dual effect of our p-CMC layer: (1) intrinsic antibacterial and antithrombotic properties of CMC and (2) anti-adhesion of substances on superhydrophilic surface. Meanwhile, despite the rough surface of the p-CMC layer, it showed high lubricity and durability under continuous wet friction conditions. Furthermore, we demonstrated that the actual p-CMC coated intravascular catheter (IC) provides superior trackability in a curved artificial blood vessel. The potential of the proposed coating strategy can be offered not only ICs, but also wide range of polymer-based applications including vascular filters, grafts, pacemakers and soft robots.

Targeting Cardiovascular Diseases by Flavonols: An Update.

Flavonols are one of the most plentiful flavonoid subclasses found in natural products and are extensively used as dietary supplements. Numerous in vitro and in vivo studies have shown the cardioprotective properties of flavonols, especially quercetin. This group of substances exerts positive impacts primarily due to their antiatherogenic, antithrombotic, and antioxidant activities. The potential of flavonols to promote vasodilation and regulation of apoptotic processes in the endothelium are other beneficial effects on the cardiovascular system. Despite promising experimental findings, randomized controlled trials and meta-analyses have yielded inconsistent results on the influence of these substances on human cardiovascular parameters. Thus, this review aims to summarize the most recent clinical data on the intake of these substances and their effects on the cardiovascular system. The present study will help clinicians and other healthcare workers understand the value of flavonol supplementation in both subjects at risk for cardiovascular disease and patients with cardiovascular diseases.

Analysis of the Composition of Deinagkistrodon acutus Snake Venom Based on Proteomics, and Its Antithrombotic Activity and Toxicity Studies.

There is a strong correlation between the composition of Deinagkistrodon acutus venom proteins and their potential pharmacological effects. The proteomic analysis revealed 103 proteins identified through label-free proteomics from 30 different snake venom families. Phospholipase A2 (30.0%), snaclec (21.0%), antithrombin (17.8%), thrombin (8.1%) and metalloproteinases (4.2%) were the most abundant proteins. The main toxicity of Deinagkistrodon acutus venom is hematotoxicity and neurotoxicity, and it acts on the lung. Deinagkistrodon acutus venom may have anticoagulant and antithrombotic effects. In summary, the protein profile and related toxicity and pharmacological activity of Deinagkistrodon acutus venom from southwest China were put forward for the first time. In addition, we revealed the relationship between the main toxicity, pharmacological effects, and the protein components of snake venom.

In vitro and in vivo antithrombotic and antioxidant properties of microencapsulated brewers’ spent grain peptides

AbstractAntioxidant and antithrombotic activities of microencapsulated brewers’ spent grain peptides (BSGH‐C) after simulated gastrointestinal digestion (SGID) and the in vivo properties using a model of growing Wistar rats fed with sucrose‐rich diet (SRD) were determined. Microencapsulation reduced the cleavage of peptides (66.5 vs. 39.2%), partially preserved the in vitro antioxidant activity (ABTS+ inhibition and FRAP) and reduced the in vitro antithrombotic activity. SRD diet produced a pro‐oxidant and pro‐thrombotic systemic environment in rats, which was reversed by the consumption of BSGH‐C. A positive correlation between in vitro antioxidant and antithrombotic activity of BSGH‐C after SGID with the respective in vivo effects observed in rats fed BSGH‐C (r = 0.9997 and r = 0.9411, respectively) was established. The goodness of both, the in vitro models determining bioactive properties after SGID, and the microencapsulation protecting the peptides from gastrointestinal environment were demonstrated. Thus, it was possible to produce microcapsules with bioavailable bioactive BSG peptides.

Saccharides from Arctium lappa L. root reduce platelet activation and thrombus formation in a laser injury thrombosis mouse model.

Arctium lappa L., also known as burdock, is a popular medicinal plant in traditional Chinese medicine due to its potential therapeutic properties. Saccharides from Arctium lappa L. root (ALR-S) have been extensively studied for their anti-inflammatory and anti-diabetes effects. Platelets play a pivotal role in thrombosis. The present study describes the effects of ALR-S on platelet activation and thrombosis using a laser injury thrombosis in vivo model. The study also measured the effects of ALR-S on platelet activation by analysing aggregation, ATP release, platelet spreading, adhesion and clot retraction in vitro. Specifically, the effects were ALR-S concentration-dependent inhibition of platelet aggregation and ATP release. Activated platelets pretreated with ALR-S showed diminished CD62P expression levels and fibrinogen binding, as measured by flow cytometry. ALR-S inhibited platelet spreading on fibrinogen and adhesion on collagen under shear. ALR-S attenuated platelet activation by decreasing oxidative stress and thrombus formation. These results demonstrated the antiplatelet effects of ALR-S, suggesting the antithrombotic and cardiovascular protective activities of ALR-S as a functional food.

Phytochemical constituents of Camellia osmantha fruit cores with antithrombotic activity

Camellia osmantha is a new species of the genus Camellia and is an economically important ornamental plant. Its activity and ingredients are less studied than other Camellia plants. This study investigated the antithrombotic effect and chemical components of C. osmantha fruit cores using platelet aggregation assays and coagulation function tests. The cores of C. osmantha fruits were extracted with ethanol to obtain a crude extract. The extract was dissolved in water and further eluted with different concentrations of methanol on an MCI resin column to obtain three fractions. These samples were used for antithrombotic activity tests and phytochemical analysis. The results showed that the extract and its fractions of C. osmantha have strong antithrombotic activity, significantly reducing the platelet aggregation rate and prolonging the thrombin time (TT). The total saponins, flavonoids, and polyphenols in the active fractions may be responsible for the antithrombotic activity. The chemical constituents were analyzed by ultra‐performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UPLC‐QTOF/MS). Twenty‐three compounds were identified rapidly and accurately. Among them, ellagic acid, naringenin, and quercetin 3‐O‐glucuronide may be important antithrombotic constituents. Furthermore, interactions between these compounds and the P2Y1 receptor were investigated via molecular modeling, because the P2Y1 receptor is a key drug target of antiplatelet aggregative activity. The molecular docking results suggested that these compounds could combine tightly with the P2Y1R protein. Our results showed that C. osmantha fruit cores are rich in polyphenols, flavonoids, and saponins, which can be developed into a promising antithrombotic functional beverage for the prevention and treatment of cardiovascular and cerebrovascular diseases.

The Acute Effect of a Novel Miso-Type Sauce, Enhanced with a Carotenoid-Rich Extract from Fruit By-Products, on Postprandial Biomarkers of Oxidative Stress and Inflammation.

Several fruit by-products may exert a beneficial role on oxidative stress and inflammation modulation, providing essential bioactive components, such as polyphenols and carotenoids. Recently, the potential bioactivity of miso has been reported. The aim of this dietary intervention–clinical study was to evaluate the acute effect of a novel, functional miso-type sauce based on legumes, on postprandial biomarkers of oxidative stress and inflammation. In this randomized, cross-over design, intervention–clinical trial, 14 healthy volunteers, aged 20–30 years old, consumed a rice meal rich in fat and carbohydrates (258 g), containing a legume-based sauce. After a 1-week washout period, the same subjects consumed the same meal, containing the novel fermented miso-type sauce, enhanced with 50% carotenoid-rich, fruit peel extract. Differences in postprandial total plasma antioxidant capacity according to the FRAP method, serum lipids, glucose, uric acid levels, and antithrombotic activity in platelet-rich plasma were evaluated before, 30 min, 1.5 h, and 3 h after consumption. The results showed that, in comparison to the control group, consumption of the novel sauce resulted in a significantly increased total plasma antioxidant capacity 3 h after consumption (p < 0.05). In addition, we observed a significant attenuation of triglycerides concentration increase in the last 1.5 h in the functional group (p < 0.05). A significant decrease in serum aggregation was found at 30 min and 3 h after functional sauce intake in comparison with the baseline (p < 0.05). Finally, LDL-cholesterol concentrations were significantly reduced 3 h after the functional meal consumption, in comparison with baseline values (p < 0.05). The remaining biomarkers did not show statistically significant differences (p > 0.05). Further investigation is needed in order to validate the current results.

Direct Determination of Enzymes in Dried Blood Spots by High-Performance Liquid Chromatography – Mass Spectrometry (HPLC-MS) for the Screening of Antithrombotic Agents

Thrombosis is the main cause of many cardiovascular diseases. The conventional pharmaceuticals used for preventing thrombosis can induce significant adverse side effects, especially bleeding risk. Hence, the development of more effective and safe antithrombotic agents is strongly demanded to improve clinical treatment. In order to rapidly screen and identify novel antithrombotic substances from natural marine products, a multi-target screening strategy is reported to quantify the antithrombotic activity with high-performance liquid chromatography – mass spectrometry (HPLC-MS). Five key thrombosis-related targets, including thrombin, coagulation factors Xa, XIa and XIIa and platelet phosphodiesterase 3, were selected to establish the multi-target antithrombotic activity screening assay. The Michaelis-Menten constants (K m) were 8.16 µM, 58.85 µM, 120.03 µM, 35.24 µM and 79.67 µM, respectively. Five known inhibitors, namely argatroban, rivaroxaban, benzamidine, 3-carboxamide-coumarinand, and milrinone, were used for validation. The reproducibility of the screening strategy was verified by calculating the overall average Z′ value, which was 0.88. Subsequently, this method was assessed by screening a small marine library of 78 compounds. Five coumarin compounds were selected, and their antithrombotic activities were further validated in standard assessments of enzyme inhibition and on the coagulometer. According to the validation, the multi-target assay based on dried blood spots and HPLC-MS was suitable for screening antithrombotic substances with considerable reliability.

Intensive low-density lipoprotein cholesterol lowering improves fibrin clot properties: Association with lipoproteins and C-reactive protein

ObjectiveDense fibrin networks resistant to lysis characterize coronary artery disease (CAD) patients. We investigated whether a statin-induced decrease of low-density lipoprotein cholesterol (LDL-C) could improve fibrin clot phenotype in CAD patients. MethodsWe recruited 130 consecutive patients with advanced CAD (baseline LDL-C of 4.4 [IQR, 3.8–4.8] mmol/L), who on statins did not achieve the LDL-C goal based on the 2016 ESC/EAS guidelines. On standard statin treatment and after 6–12 months of high-dose statin treatment (atorvastatin 80 mg/day or rosuvastatin 40 mg/day), plasma fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation, coagulation and fibrinolytic factors were determined. ResultsAfter a median high-dose statin therapy of 7 months there was 25% reduction in LDL-C associated with increased Ks and shorter CLT, together with lower thrombin activatable fibrinolysis inhibitor, factor VIII, D-dimer, and C-reactive protein (CRP); thrombin generation was unaltered. The patients who achieved the therapeutic goal (n = 49, 37.7%) had 29.2% increase in Ks and 16.3% shorter CLT compared with the standard therapy, while there were no similar changes in the remaining patients. After adjustment for potential confounders, including CRP, an increase in Ks (by 1 × 10−9 cm2) and decrease in CLT (by 10 min) were independently predicted by on-treatment LDL-C goal (odds ratio [OR] 6.23, 95% confidence interval [CI] 1.97–20.33 and OR 3.11, 95% CI 1.05–8.99, respectively). ConclusionsFor the first time we showed that a decrease of LDL-C ≤ 1.8 mmol/L, or a reduction of at least 50% if the baseline LDL-C is between 1.8 and 3.5 mmol/L, is associated with favorable alterations to fibrin clot phenotype, with a stronger impact of lipoprotein reduction than CRP lowering, which might suggest that other potent cholesterol-lowering drugs can exert similar antithrombotic actions.

Polydopamine-heparin complex reinforced antithrombotic and antimicrobial activities of heparinized hydrogels for biomedical applications

Large-scale fabrication of heparinized hydrogel could be accomplished by free-radical crosslinking polymerization (FRCP), whilst its bioactivity is often partially lost. Heparinized hydrogel based implantable medical devices, therefore, frequently encounter the compelling problems of thrombosis and microbial infection. In this study, a facile FRCP approach was proposed to fabricate heparinized hydrogels by preforming polydopamine-heparin (PDA-HEP) complex, which bypassed the steps of heparin functionalization and effectively preserved the function of heparin in the meantime. Compared with heparin mixed hydrogels, heparin in PDA-HEP complex composite hydrogels augmented the antimicrobial activity of PDA by enhancing the combined bactericidal action of cations and reactive oxygen species (ROS), while still maintaining its anticoagulant function. Since its integration of extremely low hemolysis rate, remarkable anticoagulation property and efficient bactericidal performance, we believe that this universal method of preparing heparinized hydrogels based on PDA-HEP complex will speed up the versatile application of hydrogel implants in clinical medicine.