Prothrombotic activity is associated with the anatomical as well as the functional severity of peripheral arterial occlusive disease

Nylænde, M.; Kroese, Andries J.; Stranden, Einar; Morken, B.; Sandbæk, Gunnar; Lindahl, Anne Karin; Arnesen, Harald; Seljeflot, Ingebjørg

doi:10.1160/th06-01-0007

Cited by 16 publications

(2 citation statements)

References 37 publications

(38 reference statements)

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“…18 PPACK-NP treatment significantly reduced serum thrombin-antithrombin (TAT) complexes (5.43 ± 0.64 ng/ml, N=5; p=0.0001 vs. saline, p=0.032 vs control NP) (Fig. 5A) versus saline (13.32 ± 1.01 ng/ml, N=6) and control NP (9.96 ± 1.64 ng/ml, N=5, p=NS vs. saline).…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Thrombin With PPACK-Nanoparticles Restores Disrupted Endothelial Barriers and Attenuates Thrombotic Risk in Experimental Atherosclerosis

Palekar

Jallouk

Myerson

et al. 2016

ATVB

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Objective A role for thrombin in the pathogenesis of atherosclerosis has been suggested through clinical and experimental studies revealing a critical link between the coagulation system and inflammation. Although approved drugs for inhibition of thrombin and thrombin-related signaling have demonstrated efficacy, their clinical application to this end may be limited due to significant potential for bleeding side effects. Thus, we sought to implement a plaque-localizing nanoparticle-based approach to interdict thrombin-induced inflammation and hypercoagulability in atherosclerosis. Approach and Results We deployed a novel magnetic resonance spectroscopic method to quantify the severity of endothelial damage for correlation with traditional metrics of vessel procoagulant activity after dye-laser injury in fat-fed ApoE-null mice. We demonstrate that a one-month course of treatment with anti-thrombin nanoparticles carrying the potent thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone (PPACK-NP): 1) reduces the expression and secretion of proinflammatory and procoagulant molecules, 2) diminishes plaque procoagulant activity without the need for systemic anticoagulation, 3) rapidly restores disrupted vascular endothelial barriers, and 4) retards plaque progression in lesion prone areas. Conclusions These observations illustrate the role of thrombin as a pleiotropic atherogenic molecule under conditions of hypercholesterolemia, and suggest the utility of its inhibition with locally acting anti-thrombin nanoparticle therapeutics as a rapid-acting anti-inflammatory strategy in atherosclerosis to reduce thrombotic risk.

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Section: Resultsmentioning

confidence: 99%

Inhibition of Thrombin With PPACK-Nanoparticles Restores Disrupted Endothelial Barriers and Attenuates Thrombotic Risk in Experimental Atherosclerosis

Palekar

Jallouk

Myerson

et al. 2016

ATVB

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“…In the clinical field, the evidence is inconsistent; some cross-sectional studies have shown a positive association between thrombin generation and aortic, carotid, and peripheral arterial atherosclerosis [15–17], whereas others have not [18–20]. …”

Section: Introductionmentioning

confidence: 99%

Association between Stable Coronary Artery Disease and In Vivo Thrombin Generation

Valente-Acosta

Baños-González

Peña‐Duque

et al. 2016

Cardiology Research and Practice

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Background. Thrombin has been implicated as a key molecule in atherosclerotic progression. Clinical evidence shows that thrombin generation is enhanced in atherosclerosis, but its role as a risk factor for coronary atherosclerotic burden has not been proven in coronary artery disease (CAD) stable patients. Objectives. To evaluate the association between TAT levels and homocysteine levels and the presence of coronary artery disease diagnosed by coronary angiography in patients with stable CAD. Methods and Results. We included 95 stable patients admitted to the Haemodynamics Department, including 63 patients with significant CAD and 32 patients without. We measured the thrombin-antithrombin complex (TAT) and homocysteine concentrations in all the patients. The CAD patients exhibited higher concentrations of TAT (40.76 μg/L versus 20.81 μg/L, p = 0.002) and homocysteine (11.36 μmol/L versus 8.81 μmol/L, p < 0.01) compared to the patients without significant CAD. Specifically, in patients with CAD+ the level of TAT level was associated with the severity of CAD being 36.17 ± 24.48 μg/L in the patients with bivascular obstruction and 42.77 ± 31.81 μg/L in trivascular coronary obstruction, p = 0.002. Conclusions. The level of in vivo thrombin generation, quantified as TAT complexes, is associated with the presence and severity of CAD assessed by coronary angiography in stable CAD patients.

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Interleukin-receptor antagonist and tumor necrosis factor inhibitors for the primary and secondary prevention of atherosclerotic cardiovascular diseases

Martí‐Carvajal

Sanctis

Dayer

et al. 2021

Cochrane Database of Systematic Reviews

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Prothrombotic activity is associated with the anatomical as well as the functional severity of peripheral arterial occlusive disease

Cited by 16 publications

References 37 publications

Inhibition of Thrombin With PPACK-Nanoparticles Restores Disrupted Endothelial Barriers and Attenuates Thrombotic Risk in Experimental Atherosclerosis

Inhibition of Thrombin With PPACK-Nanoparticles Restores Disrupted Endothelial Barriers and Attenuates Thrombotic Risk in Experimental Atherosclerosis

Association between Stable Coronary Artery Disease and In Vivo Thrombin Generation

Interleukin-receptor antagonist and tumor necrosis factor inhibitors for the primary and secondary prevention of atherosclerotic cardiovascular diseases

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