Platelet hyperaggregability in patients with atrial fibrillation

Procter, Nathan E.K.; Ball, Jocasta; Ngo, D.; Chirkov, Yuliy Y.; Isenberg, Jeffrey S.; Stewart, Simon; Horowitz, John D.

doi:10.1007/s00059-015-4335-y

Cited by 11 publications

(4 citation statements)

References 33 publications

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“…6,7) However, Hanatani, et al 6) reported that the levels of TSP-2 with ischemic diseases were comparable to those with nonischemic diseases, which is consistent with the present study. Although TSP-1 has been reported to be correlated to arrhythmias, 36,37) it was reported for the first time in the present study that there is an association between TSP-2 and arrhythmias, especially atrial fibrillation. This issue should be also clarified in the near future.…”

Section: Tsp-2 and Inflammationcontrasting

confidence: 46%

Thrombospondin-2 as a Potential Risk Factor in a General Population

et al. 2019

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Serum thrombospondin-2 (TSP-2) is a glycoprotein expressed in the extracellular matrix (ECM), which increases during tissue remodeling. It has been shown in recent studies that TSP-2 is a useful predictor of cardiovascular death in patients with heart failure (HF). However, the clinical importance of serum TSP-2 levels in a general population is still unknown. Therefore, we aimed to clarify the association between TSP-2 and clinical risk factors. A periodic epidemiological survey was performed in a community dwelling in the town of Uku, Nagasaki, Japan. A total of 445 residents received a health checkup examination including blood tests such as fasting serum levels of TSP-2. Uni-and multivariate analyses were performed to examine the relationship between TSP-2 and clinical risk factors. All statistical analyses were performed using SAS v9.4 program. The mean ± standard deviation of age was 67.0 ± 9.4 years old. Although serum TSP-2 levels (mean: 20.9 ± 8.5 ng/ mL) showed no significant sex difference, they were significantly correlated with the levels of plasma glucose (P < 0.001), insulin (P < 0.01), homeostasis model assessment of insulin resistance (HOMA-IR) (P < 0.001), estimated glomerular filtration rate (eGFR) (P < 0.01, inversely), high-sensitivity C-reactive protein (hs-CRP) (P < 0.001), history of atrial fibrillation (P < 0.001), history of cardiovascular diseases (P < 0.001), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (P < 0.001). Moreover, in the multiple stepwise linear regression analysis, the levels of TSP-2 were independently and significantly associated with the history of atrial fibrillation (P < 0.0001), HOMA-IR (P < 0.001), high-sensitivity CRP (P = 0.011), and NT-proBNP (P = 0.043). These results indicated the significant relationship between TSP-2 and clinical risk factors in a general population, suggesting its role as a predictor of heart disease morbidity and mortality.

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Section: Tsp-2 and Inflammationcontrasting

confidence: 46%

Thrombospondin-2 as a Potential Risk Factor in a General Population

et al. 2019

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“…High expression of plasma TSP1 in AIS secondary to large vessel occlusion is correlated with diagnosis and prognosis with good or poor collaterals, reconciled by phase 1 of the SpecTRA clinical trial, revealing an increased odds ratio of TSP1 in minor stroke and transient ischemic attack [41]. Additionally, a high level of TSP1 in serum or plasma was tightly associated with atrial fibrillation or the new onset of atrial fibrillation [42,43]. More than a diagnostic or prognostic biomarker for several clinical conditions, excessive TSP1 plays pathologic roles in hypertension, pulmonary arterial hypertension, heart failure, and ischemia-reperfusion injury as well.…”

Section: Discussionmentioning

confidence: 96%

Novel Pharmaceutical Strategy for Selective Abrogation of TSP1-Induced Vascular Dysfunction by Decoy Recombinant CD47 Soluble Receptor in Prophylaxis and Treatment Models

et al. 2021

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Elevated thrombospondin 1 (TSP1) is a prevalent factor, via cognate receptor CD47, in the pathogenesis of cardiovascular conditions, including ischemia-reperfusion injury (IRI) and pulmonary arterial hypertension (PAH). Moreover, TSP1/CD47 interaction has been found to be associated with platelet hyperaggregability and impaired nitric oxide response, exacerbating progression in IRI and PAH. Pathological TSP1 in circulation arises as a target of our novel therapeutic approach. Our “proof-of-concept” pharmacological strategy relies on recombinant human CD47 peptide (rh-CD47p) as a decoy receptor protein (DRP) to specifically bind TSP1 and neutralize TSP1-impaired vasorelaxation, strongly implicated in IRI and PAH. The binding of rh-CD47p and TSP1 was first verified as the primary mechanism via Western blotting and further quantified with modified ELISA, which also revealed a linear molar dose-dependent interaction. Ex vivo, pretreatment protocol with rh-CD47p (rh-CD47p added prior to TSP1 incubation) demonstrated a prophylactic effect against TSP1-impairment of endothelium-dependent vasodilation. Post-treatment set-up (TSP1 incubation prior to rh-CD47p addition), mimicking pre-existing excessive TSP1 in PAH, reversed TSP1-inhibited vasodilation back to control level. Dose titration identified an effective molar dose range (approx. ≥1:3 of tTSP1:rh-CD47p) for prevention of/recovery from TSP1-induced vascular dysfunction. Our results indicate the great potential for proposed novel decoy rh-CD47p-therapy to abrogate TSP1-associated cardiovascular complications, such as PAH.

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“…TSP‑1 may also interact with MMP-2 and MMP-9, possibly inhibiting their activity and regulating collagen homeostasis [ 21 ]. Procter et al [ 22 ] also found platelet hyperaggregability, induced by the release of TSP-1 from platelet α-granules, may diminish nitric oxide signaling, thus promoting inflammation. Recently, Zhou et al [ 23 ] reported that microRNA-221 could inhibit latent TGF-β1 activation by targeting TSP-1 to attenuate cardiac fibrosis, which could be a possible upstream treatment of AA.…”

Section: Discussionmentioning

confidence: 99%

Association of atrial arrhythmias with thrombospondin-1 in patients with acute myocardial infarction

Liao

Pan

et al. 2021

BMC Cardiovasc Disord

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Objectives Atrial remodeling is the main developmental cause of atrial arrhythmias (AA), which may induce atrial fibrillation, atrial flutter, atrial tachycardia, and frequent premature atrial beats in acute myocardial infarction (AMI) patients. Thrombospondin-1 (TSP-1) has been shown to play an important role in inflammatory and fibrotic processes, but its role in atrial arrhythmias is not well described. The purpose of this study was to investigate the role of TSP-1 in AMI patients with atrial arrhythmias. Methods A total of 219 patients with AMI who underwent percutaneous coronary intervention and with no previous arrhythmias were included. TSP-1 were analyzed in plasma samples. Patients were classified into 2 groups, namely, with and without AA during the acute phase of MI. Continuous electrocardiographic monitoring was used for AA diagnosis in hospital. Results Twenty-four patients developed AA. Patients with AA had higher TSP-1 levels (29.01 ± 25.87 μg/mL vs 18.36 ± 10.89 μg/mL, p < 0.001) than those without AA. AA patients also tended to be elderly (65.25 ± 9.98 years vs 57.47 ± 10.78 years, p < 0.001), had higher Hs-CRP (39.74 ± 43.50 mg/L vs 12.22 ± 19.25 mg/L, p < 0.001) and worse heart function. TSP-1 (OR 1.033; 95% CI 1.003–1.065, p = 0.034), Hs-CRP (OR 1.023; 95% CI 1.006–1.041, p = 0.008), age (OR 1.067; 95% CI 1.004–1.135, p = 0.038) and LVDd (OR 1.142; 95% CI 1.018–1.282, p = 0.024) emerged as independent risk factors for AA in AMI patients. Conclusion TSP-1 is a potential novel indicator of atrial arrhythmias during AMI. Graphical abstract

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Platelet hyperaggregability in patients with atrial fibrillation

Abstract: We conclude that platelet hyperaggregability, where present in the context of AF, may be engendered by impaired availability of NO, as well as via MPO-related inflammatory activation.

Cited by 11 publications

References 33 publications

Thrombospondin-2 as a Potential Risk Factor in a General Population

Thrombospondin-2 as a Potential Risk Factor in a General Population

Novel Pharmaceutical Strategy for Selective Abrogation of TSP1-Induced Vascular Dysfunction by Decoy Recombinant CD47 Soluble Receptor in Prophylaxis and Treatment Models

Association of atrial arrhythmias with thrombospondin-1 in patients with acute myocardial infarction

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