Biomedical subjects

Sophie Susen

Publications and source records attributed to Sophie Susen.

9 recordsLinked to original sources

PubMed2006

Dyslipidemia shifts the tissue factor/tissue factor pathway inhibitor balance toward increased thrombogenicity in atherosclerotic plaques: evidence for a corrective effect of statins.

BACKGROUND: Tissue factor (TF) is a key mediator of atherosclerotic plaque thrombogenicity and may be regulated by plaque TF pathway inhibitor (TFPI). High atherogenic lipoproteins are a well-known arterial risk factor, but their effects on the TF/TFPI balance in atherosclerotic plaques, as well as those of widely used lipid-lowering agents such as statins, are incompletely understood. OBJECTIVES: We analyzed the TF/TFPI balance in carotid plaques from 86 patients, according to the presence of dyslipidemia and statin therapy. RESULTS: In patients with untreated dyslipidemia (ApoB/ApoA1 ratio >0.7) (D+) (n=44), TF antigen (TF) tended to be higher than in those without dyslipidemia (D-) (n=16). In patients with statins (S+) (n=26), TF was lower than in D+ (p=0.02) and similar to that of D- patients. TFPI antigen was higher in D- than in D+ and S+ patients (p<or=0.02). As a result, the TF/TFPI (mol/mol) ratio was higher in D+ than in D- or S+ patients (p<or=0.005). TF activity correlated to TF/TFPI ratio (p<0.0001), and was higher in the D+ than in the D- and in the S+ patients (p=0.02). Among analyzed clinical risk factors and biological parameters, including CRP, dyslipidemia was the only independent predictor for low plaque TFPI and high TF/TFPI ratio. Histochemistry showed that TF and TFPI were mainly expressed in macrophage-rich regions surrounding the lipid-rich core in the three groups. CONCLUSIONS: These results indicate that dyslipidemia is associated with a shift of the TF/TFPI balance and of TF activity toward higher plaque thrombotic potential. Statins correct this equilibrium mainly by decreasing plaque TF together with blood atherogenic lipoproteins.

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PubMed2006

From normal to pathological hemostasis.

PURPOSE: To review the evolution of knowledge on physiological hemostasis and the main abnormalities that may interfere with hemostasis in the perioperative period. METHODS: Narrative review of the literature, including relevant papers published in English. PRINCIPAL FINDINGS: Physiological hemostasis controls blood fluidity and rapidly induces hemostatic plug formation in order to stop or limit bleeding. The three distinct phases of the hemostatic process, primary hemostasis, coagulation and fibrinolysis are closely linked to each other and precisely regulated in order to efficiently close vessel wounds, promote vascular healing and maintain vessel patency. Primary hemostasis is the result of complex interactions between the vascular wall, platelets and adhesive proteins. Initiation of the coagulation pathway in vivo is secondary to the exposure of tissue factor (TF) and the formation of TF/VIIa complex which can activate both FIX and FX. This initiation phase is followed by a propagation phase with amplification of thrombin generation. Several control mechanisms exist for localizing fibrin formation to the site of injury including tissue factor pathway inhibitor, protein C system, antithrombin, and glycosaminoglycans on the vessel wall. Fibrinolysis is also a highly regulated system that controls fibrin dissolution. Both constitutive and acquired hemostasic defects exist. The consequences of these abnormalities are highly variable according to the type of defect, and to the genetic and environmental background. CONCLUSION: Hemostasis is one of the most complex physiological self-defence systems, not only involved in control of blood fluidity but also interfering in major physiopathological processes. The evolution of our knowledge of the physiology of hemostasis has numerous implications for therapy.

Animals↗

PubMed2006

Decellularized heart valve as a scaffold for in vivo recellularization: deleterious effects of granulocyte colony-stimulating factor.

BACKGROUND: Autologous recellularization of decellularized heart valve scaffolds is a promising challenge in the field of tissue-engineered heart valves and could be boosted by bone marrow progenitor cell mobilization. The aim of this study was to examine the spontaneous in vivo recolonization potential of xenogeneic decellularized heart valves in a lamb model and the effects of granulocyte colony-stimulating factor mobilization of bone marrow cells on this process. METHODS: Decellularized porcine aortic valves were implanted in 12 lambs. Six lambs received granulocyte colony-stimulating factor (10 microg x kg(-1) x d(-1) for 7 days, granulocyte colony-stimulating factor group), and 6 received no granulocyte colony-stimulating factor (control group). Additionally, nondecellularized porcine valves were implanted in 5 lambs (xenograft group). Angiographic and histologic evaluation was performed at 3, 6, 8, and 16 weeks. RESULTS: Few macroscopic modifications of leaflets and the aortic wall were observed in the control group, whereas progressive shrinkage and thickening of the leaflets appeared in the granulocyte colony-stimulating factor and xenograft groups. In the 3 groups progressive ovine cell infiltration (fluorescence in situ hybridization) was observed in the leaflets and in the adventitia and the intima of the aortic wall but not in the media. Neointimal proliferation of alpha-actin-positive cells, inflammatory infiltration, adventitial neovascularization, and calcifications were more important in the xenograft and the granulocyte colony-stimulating factor groups than in the control group. Continuous re-endothelialization appeared only in the control group. CONCLUSION: Decellularized xenogeneic heart valve scaffolds allowed partial autologous recellularization. Granulocyte colony-stimulating factor led to accelerated heart valve deterioration similar to that observed in nondecellularized xenogeneic cardiac bioprostheses.

Actins↗

PubMed2005

High-sensitivity C-reactive protein: potential adjunct for risk stratification in patients with stable congestive heart failure.

AIMS: To determine the potential adjunct of high-sensitivity (hs) C-reactive protein for risk stratification in patients with stable congestive heart failure (CHF). METHODS AND RESULTS: We studied 546 consecutive patients clinically stable with an ejection fraction <45% who were referred to our centre for evaluation of left ventricular dysfunction. hs C-reactive protein levels were determined on blood samples obtained on entry into the study. Clinical follow-up (median 972 days) was obtained for 545 patients. Cardiovascular mortality was significantly increased (P=0.001) in patients with hs C-reactive protein >3 mg/L. By multivariable analysis, including clinical, biological, and echocardiographic variables, hs C-reactive protein >3 mg/L was an independent predictor of cardiovascular mortality [HR=1.78 (1.17-2.72); P=0.008]; the strongest predictive parameter in this model was B-type natriuretic peptide (BNP) (P=0.005). When peak VO(2) was included into the model, hs C-reactive protein >3 mg/L remained an independent predictor of cardiovascular mortality [HR=1.55 (1.02-2.38); P=0.04]; the strongest predictive parameter in this model was peak VO(2) (P<0.0001). In patients with ischaemic CHF, cardiovascular mortality was significantly increased in patients with hs C-reactive protein >3 mg/L (P=0.001), whereas in patients with non-ischaemic CHF, hs C-reactive protein >3 mg/L was not associated with cardiovascular mortality (P=0.098). By multivariable analysis, hs C-reactive protein >3 mg/L was an independent predictor of cardiovascular mortality in ischaemic patients [HR=2.16 (1.23-3.78)] but not in non-ischaemic patients [HR=1.05 (0.52-2.11)]. CONCLUSION: Cardiovascular mortality is increased in CHF patients with hs C-reactive protein >3 mg/L. The impact of hs C-reactive protein is independent of usual prognostic parameters, in particular BNP and peak VO(2). The interest of hs C-reactive protein determination appears to be especially marked in patients with ischaemic cardiomyopathy.

C-Reactive Protein↗

PubMed2005

Serum hepatocyte growth factor levels predict long-term clinical outcome after percutaneous coronary revascularization.

AIMS: To evaluate, in patients referred for elective percutaneous coronary revascularization (PCR) without heparin pre-treatment, the relationship between baseline serum levels of the angiogenic growth factors, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), and clinical outcome. METHODS AND RESULTS: In 488 consecutive patients undergoing elective coronary angioplasty, hsC-reactive protein, HGF, and VEGF levels were measured before heparin administration. The primary endpoint, a composite of death and myocardial infarction, occurred in 44 patients at a median follow-up of 14.9 months. At baseline, VEGF levels were related to C-reactive protein levels and inversely related to age; HGF levels were related to C-reactive protein levels, diabetes, and recent clinical instability. In the univariate analysis, HGF had a significant positive relationship (P=0.003) with the primary endpoint. A similar trend was observed for VEGF (P=0.11). The only three variables significantly associated with the primary endpoint in the multivariable Cox model were HGF (P=0.004), C-reactive protein (P=0.007), and diabetes (P=0.04). CONCLUSION: Our results demonstrate that in patients, without heparin pre-treatment, referred for PCR, a high serum level of HGF is an independent predictor of clinical events during follow-up and is correlated with other surrogate measures of the activity of atherosclerosis.

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PubMed2005

The proteome and secretome of human arterial smooth muscle cells.

Smooth muscle cells (SMCs) play a crucial role in cardiovascular disorders. A differential proteomic approach should help to elucidate SMC dysfunctions involved in these diseases. With this goal in mind, we plotted the first 2-dimensional (2-D) maps of the proteome and secretome of human arterial smooth muscle cell (ASMC). Intracellular and secreted proteins were extracted from a primary culture of SMCs obtained from patients undergoing coronary artery bypass surgery (n = 11) and separated by 2-dimensional gel electrophoresis. Silver-stained gels were analyzed using Progenesis software. A high level of between-gel reproducibility was obtained, allowing us to generate two protein patterns specific to the ASMC proteome and secretome, respectively. A total of 121 and 40 distinct intracellular and secreted polypeptide spots, corresponding to 83 and 18 different proteins, respectively, were identified by matrix-assisted laser desorption/ionization mass spectrometry. The 2-D reference maps and database resulting from this study confirm that SMCs are involved in a wide range of biological functions. They could constitute a useful tool for a wide range of investigators involved in vascular biology, allowing them to investigate SMC protein changes associated with cardiovascular disorders or environmental stimuli.

Cells, Cultured↗

PubMed2005

Prognostic significance of circulating levels of angiogenic cytokines in patients with congestive heart failure.

BACKGROUND: Recent experimental studies have suggested that the angiogenic cytokines hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) may play a role in the pathogenesis of congestive heart failure (CHF). The aim of the present study was to test the hypothesis that HGF and VEGF concentrations may vary according to the different markers of CHF severity and to analyze the impact of HGF and VEGF concentrations on the cardiovascular mortality of patients with CHF. METHODS: We studied 529 consecutive patients who were referred to our center for an evaluation of left ventricular dysfunction. Hepatocyte growth factor and vascular endothelial growth factor levels were determined on blood samples obtained on entry into the study. Clinical follow-up (median 988 days) was obtained for 528 patients. RESULTS: Hepatocyte growth factor concentrations were strongly associated with age, diabetes mellitus, and all markers of CHF severity; by contrast, baseline characteristics did not differ among VEGF tertiles. Cardiovascular survival rates at 1, 2, and 3 years were 91%, 87%, and 80%, respectively. The survival curves indicated a worse outcome for patients with high HGF concentrations at baseline (P < .0001); by contrast, cardiovascular survival was similar across the tertiles of VEGF (P = .37). Hepatocyte growth factor concentrations were higher in the 109 patients with a cardiovascular event (1001 [741-1327] pg/mL) than in the 419 patients without (773 [610-1045] pg/mL, P < .0001). By multivariate analysis, a baseline HGF concentration >802 pg/mL was associated with an increased cardiovascular mortality (hazard ratio = 1.85, 95% CI 1.09-3.13, P = .02); other variables retained into the final model were B-type natriuretic peptide (P < .0001), peak oxygen consumption (P = .0002), and ischemic etiology (P = .0005). CONCLUSIONS: Hepatocyte growth factor levels correlate with CHF severity and are associated with an increased cardiovascular mortality during follow-up.

Female↗

PubMed2003

Dietary lipid lowering modifies plaque phenotype in rabbit atheroma after angioplasty: a potential role of tissue factor.

BACKGROUND: Tissue factor (TF), the main initiator of blood coagulation, is involved in cellular migration and angiogenesis processes. TF is expressed strongly in lipid-rich plaques and probably plays an important role in the thrombotic complications of plaque rupture. This study analyzes the effect of dietary lipid lowering on TF expression and cellular modifications in angioplasty-induced rabbit plaque rupture. METHODS AND RESULTS: After experimental plaque rupture by balloon angioplasty in atheromatous rabbits, animals were assigned a 0.2% or a 2% cholesterol diet, and the TF content of arterial wall and the associated histological modifications were analyzed after 4 weeks. Early effects of lipid lowering were observed: The increase of TF expression in the vascular wall was stronger in the 2% than in the 0.2% cholesterol diet group (iliac arteries: 1226+/-308 versus 72+/-29 mU TF/g artery, P<0.005). Immunohistochemistry indicated that TF expression was associated with sprout of neovessels, which was more pronounced in the 2% than in the 0.2% cholesterol group. CONCLUSIONS: This study shows that dietary lipid lowering decreases the thrombotic potential of ruptured atherosclerotic plaques through TF decrease. Moreover, high TF expression is associated with marked angiogenesis in the vascular wall, which is reduced by lipid lowering. These results provide further arguments for strong dietary lipid lowering to reduce plaque instability and thrombogenicity.

Angioplasty, Balloon↗

PubMed2003

Acquired von Willebrand syndrome in aortic stenosis.

BACKGROUND: Aortic-valve stenosis can be complicated by bleeding that is associated with acquired type 2A von Willebrand syndrome. However, the prevalence and cause of the hemostatic abnormality in aortic stenosis are unknown. METHODS: We enrolled 50 consecutive patients with aortic stenosis, who completed a standardized screening questionnaire to detect a history of bleeding. Forty-two patients with severe aortic stenosis underwent valve replacement. Platelet function under conditions of high shear stress, von Willebrand factor collagen-binding activity and antigen levels, and the multimeric structure of von Willebrand factor were assessed at base line and one day, seven days, and six months postoperatively. RESULTS: Skin or mucosal bleeding occurred in 21 percent of the patients with severe aortic stenosis. Platelet-function abnormalities under conditions of high shear stress, decreased von Willebrand factor collagen-binding activity and the loss of the largest multimers, or a combination of these was present in 67 to 92 percent of patients with severe aortic stenosis and correlated significantly with the severity of valve stenosis. Primary hemostatic abnormalities were completely corrected on the first day after surgery but tended to recur at six months, especially when there was a mismatch between patient and prosthesis (with an effective orifice area of less than 0.8 cm2 per square meter of body-surface area). CONCLUSIONS: Type 2A von Willebrand syndrome is common in patients with severe aortic stenosis. Von Willebrand factor abnormalities are directly related to the severity of aortic stenosis and are improved by valve replacement in the absence of mismatch between patient and prosthesis.

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