Antithrombotic therapy for heart failure in sinus rhythm

Subramaniam, Veeran; Davis, Russell; Shantsila, Eduard; Lip, Gregory Y.H.

doi:10.1111/j.1472-8206.2009.00776.x

Cited by 7 publications

(7 citation statements)

References 119 publications

(148 reference statements)

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“…The role of inflammation in the pathogenesis of heart failure is thought to involve a variety of cytokines as well as leukocytes, platelets, tissue macrophages and endothelial cells [32], [33]. Additional factors may include blood coagulation and rheological abnormalities, activation of the neuroendocrine system, and platelet abnormalities [34]. When heart failure is complicated with diabetes mellitus (DM), the prognosis is poor due to the metabolic impact of the underlying insulin resistance and hyperglycemia, which are associated with diastolic dysfunction and reduced stress tolerance [35].…”

Section: Introductionmentioning

confidence: 99%

Increased Levels of Plasma Soluble Sema4D in Patients with Heart Failure

Dong

Wang

et al. 2013

PLoS ONE

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Semaphorin 4D (Sema4D/CD100) is a 150-kDa transmembrane glycoprotein expressed by platelets and T-cells. When these cells are activated, Sema4D is cleaved proteolytically, generating a biologically active 120-kDa fragment (soluble Sema4D) capable of targeting receptors on platelets, B-cells, endothelial cells and tumor cells. However, its plasma levels and significance in heart failure (HF) have not been reported. In this study, we established an ELISA and detected soluble Sema4D in human plasma. In healthy controls, plasma Sema4D levels were higher in men than women (5.15±3.30 ng/mL, n = 63, vs. 4.19±2.39 ng/mL, n = 63, P<0.05). In HF patients, plasma Sema4D levels were significantly higher than those in healthy controls (8.94±5.89 ng/mL, n = 157 vs. 4.67±2.99 ng/mL, n = 126, P<0.0001) with the highest levels being in HF patients with diabetes mellitus (DM) (10.45±5.76 ng/mL, n = 40). We also found that there was a higher percentage of Sema4Dhigh CD3+ (P<0.01), CD4+ (P<0.001), and CD8+ (P<0.01) T-cells in samples from HF patients, but no changes in Sema4D expression levels in B cells and platelets. Therefore, our investigation shows that plasma Sema4D levels are increased in HF patients, especially in those who also have diabetes. There was an accompanying increase in the Sema4Dhigh population of T-cells, suggesting a potential role of these T-cells in heart failure.

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Section: Introductionmentioning

confidence: 99%

Increased Levels of Plasma Soluble Sema4D in Patients with Heart Failure

Dong

Wang

et al. 2013

PLoS ONE

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“…Moreover, their role is crucial in various pathological processes as well, involved in the pathogenesis of different diseases such as chronic obstructive pulmonary disease , cancer , liver cirrhosis and arthritis , while they are also engaged in cardiovascular diseases including arterial hypertension , pulmonary hypertension , coronary artery disease , stroke and cardiac hypertrophy . They are gaining increasing clinical interest as important players in vascular remodeling, atherogenesis and thrombosis .…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical determination of the extracellular matrix modulation in a rat model of choline‐deprived myocardium: the effects of carnitine

Strilakou

Perelas

Lazaris

et al. 2015

Fundamemntal Clinical Pharma

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Choline has been identified as an essential nutrient with crucial role in many vital biological functions. Recent studies have demonstrated that heart dysfunction can develop in the setting of choline deprivation even in the absence of underlying heart disease. Matrix metalloproteinases (MMPs) are responsible for extracellular matrix degradation, and the dysregulation of MMP-2 and MMP-9 has been involved in the pathogenesis of various cardiovascular disorders. The aim of the study was to investigate the role of MMPs and their inhibitors (TIMPs), in the pathogenesis of choline deficiency-induced cardiomyopathy, and the way they are affected by carnitine supplementation. Male Wistar Albino adult rats were divided into four groups and received standard or choline-deficient diet with or without L-carnitine in drinking water (0.15% w/v) for 1 month. Heart tissue immunohistochemistry for MMP-2, MMP-9, TIMP-1, and TIMP-2 was performed. Choline deficiency was associated with suppressed immunohistochemical expression of MMP-2 and an increased expression of TIMP-2 compared to control, while it had no impact on TIMP-1. MMP-9 expression was decreased without, however, reaching statistical significance. Carnitine did not affect MMP-2, MMP-9, TIMP-1 or TIMP-2 expression. The pattern of TIMP and MMP modulation observed in a choline deficiency setting appears to promote fibrosis. Carnitine, although shown to suppress fibrosis, does not seem to affect MMP-2, MMP-9, TIMP-1 or TIMP-2 expression. Further studies will be required to identify the mechanism underlying the beneficial effects of carnitine.

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“…α‐Defensins seem to favour LDL cholesterol and lipoprotein(a) trapping in the subintimal space in the vessels, thereby contributing to foam cell formation in the atherosclerotic process,, and high concentrations of α‐defensins have been observed in atherosclerotic plaques from human coronary arteries,– suggestive of a causal link to the development and progression of cardiovascular disease (CVD) ,,. Another pathogenic role for α‐defensins is promotion of the pro‐thrombotic state in CHF, with increased thrombo‐embolic events . α‐Defensins seem to inhibit tissue plasminogen activator (t‐PA), thereby inhibiting the development of plasmin, leading to the state of increased coagulation ,.…”

Section: Introductionmentioning

confidence: 99%

“…Another pathogenic role for α‐defensins is promotion of the pro‐thrombotic state in CHF, with increased thrombo‐embolic events . α‐Defensins seem to inhibit tissue plasminogen activator (t‐PA), thereby inhibiting the development of plasmin, leading to the state of increased coagulation ,. α‐Defensins have demonstrated prognostic abilities in different patient groups regarding mortality; type 1 diabetes (T1D) and lower extremity peripheral arterial disease, and regarding the likelihood for coronary heart disease in men .…”

Section: Introductionmentioning

confidence: 99%

α‐Defensins and outcome in patients with chronic heart failure

Christensen

Frystyk

Faber

et al. 2012

European J of Heart Fail

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Aim a-Defensins are part of the innate immune system. Low-grade inflammation seems to play a crucial role in development and progression of chronic heart failure (CHF). The aims of the present study were to compare plasma levels of a-defensins in CHF patients and healthy controls and to examine the predictive ability of a-defensins, alone and combined with N-terminal pro brain natriuretic peptide (NT-proBNP), with respect to all-cause mortality. Methods and resultsIn a prospective observational study lasting 2.6 years we examined the prognostic value of plasma a-defensins with respect to mortality in 194 CHF patients, and compared plasma levels with those of 98 age-matched healthy controls. a-Defensin levels were twice as high among CHF patients in New York Heart Association (NYHA) functional class III -IV than in patients in NYHA class I-II and healthy controls (P ¼ 0.001). The absolute increase in risk of mortality for patients with a-defensin levels in the upper tertile vs. the lowest tertile was 30% (P ¼ 0.002). After adjusting for potential confounders including NT-proBNP, plasma a-defensins remained independently associated with an increased risk of all-cause mortality (hazard ratio 1.65, 95% confidence interval 1.19-2.28, P ¼ 0.002) per 1 standard deviation increment in Ln (natural logarithm)-transformed a-defensin values. The combination of high a-defensins and NT-proBNP levels provided incremental prognostic information independent of well-known prognostic biomarkers in heart failure. ConclusionPlasma a-defensins appear to have prognostic information regarding mortality among patients with CHF and seem to provide incremental information to established clinical risk markers.--

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Antithrombotic therapy for heart failure in sinus rhythm

Cited by 7 publications

References 119 publications

Increased Levels of Plasma Soluble Sema4D in Patients with Heart Failure

Increased Levels of Plasma Soluble Sema4D in Patients with Heart Failure

Immunohistochemical determination of the extracellular matrix modulation in a rat model of choline‐deprived myocardium: the effects of carnitine

α‐Defensins and outcome in patients with chronic heart failure

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