Marta M Turu

Hospital Universitari Mutua de Terrassa, Terrassa, Catalonia, Spain

Are you Marta M Turu?

Claim your profile

Publications (24)56.17 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Chlamydia pneumoniae (Cpn) could play an important role in the development of atherosclerosis. Cpn interferes with HIF-1alpha regulation in infected host cells during intracellular replication in hypoxia. We obtained carotid artery specimens with low (n=38), high (n=25) levels of stenosis and 10 middle cerebral arteries. Fifty eight percent of the carotids with low levels of stenosis showed evidence of the viable organism. Ninety one percent of the positive results were derived from pre-atheromatous lesions. Only 12 percent of plaques removed at endarterectomy showed the presence of Cpn DNA. All middle cerebral arteries failed to show evidence of live Chlamydia. Ninety one percent of sera from 22 endarterectomy patients failed to show the presence of Cpn antibodies. Immunohistology of carotid arteries with low levels of stenosis was used to confirm the presence of HIF-1alpha in infected specimens and showed a correlation between the over-expression of HIF-1alpha and Cpn in the plaque (p less than 0.05). Cpn might play an important role in activation and development of the initial stages of atherosclerotic lesions.
    Frontiers in bioscience (Elite edition) 01/2012; 4:2423-32.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Angiogenesis is a feature of the atherogenic process, with intimal neovascularisation arising from vessels in the adventitia, adjacent to a plaque. Immature, leaky blood vessels from unstable plaques proliferate abnormally and, being poorly invested with smooth muscle cells, may contribute to instability of the plaque by facilitation of inflammatory cell infiltration and haemorrhagic complications. We used laser-capture microdissection to isolate angiogenic areas of the extracellular matrix (containing CD105/flt-1-positive, fragile thin-walled vessels) and non-angiogenic vascular areas (CD105-negative, with smooth muscle cell covering) of complicated endarterectomy plaques, and specifically designed angiogenesis-TaqMan real-time PCR microarrays to identify gene expression. Important pro-angiogenic components, including Notch-3, delta-like-4 (DLL4), Tie-2, angiopoietin-1 (Angio-1) and receptor for advanced glycation end products (RAGE), and one anti-angiogenic factor, endostatin, were up-regulated in these regions. Immunohistochemistry demonstrated localisation within intimal, active (CD105-positive) microvessels and co-localisation of Notch-3 and DLL4/Tie-2 and Angio-1 in the same vessels indicating multiple/synergistic signalling mechanisms associated with vessel development. These data, although providing only a snapshot of information, demonstrate that plaque vascularisation occurs in the presence of multiple angiogenically active factors. Knowledge of their combined effects could help in the formulation of novel therapeutics designed to stabilise or prevent their formation in the treatment of atherosclerosis.
    Journal of Vascular Research 12/2009; 47(4):323-35. · 2.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recovery from stroke is dependent on the survival of neurons in the dynamic peri-infarcted region. Although several markers of neuronal injury and apoptotic cell death have been described, administration of neuroprotective drugs directed at specific molecules has had limited success. A complete understanding of deregulated genes associated with neuronal death would be beneficial. Our previous microarray studies identified increased expression of a novel protein, the B-cell translocation gene 2 (BTG2), in infarcted regions. We have used immunohistochemistry and Western blotting to examine the expression and localization of BTG2 in stroked brain tissue and immunofluorescent staining of human fetal brain neurons to determine if oxygen-glucose deprivation affected its expression. We show that BTG2 is strongly expressed in peri-infarcted and infarcted regions of brain tissue, localizing in neuronal nuclei and cytoplasm, whilst being absent or very weakly expressed in normal looking contralateral tissue. Exposure of human fetal brain neurons to oxygen-glucose deprivation also induced BTG2 expression in the cytoplasm and perinuclear regions of cells staining positive for propidium iodide (a marker of nuclear damage). BTG2 may be a modulator of cell survival and differentiation and could help to protect against cell death by inhibition of necrosis and/or apoptotic signalling pathways.
    Pathobiology 06/2009; 76(3):129-35. · 1.95 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Native C-reactive protein (nCRP) is a pentameric oligo-protein and an acute phase reactant whose serum expression is increased in patients with inflammatory disease. We have identified by immunohistochemistry, significant expression of a tissue-binding insoluble modified version or monomeric form of CRP (mCRP) associated with angiogenic microvessels in peri-infarcted regions of patients studied with acute ischaemic stroke. mCRP, but not nCRP was expressed in the cytoplasm and nucleus of damaged neurons. mCRP co-localized with CD105, a marker of angiogenesis in regions of revascularisation. In vitro investigations demonstrated that mCRP was preferentially expressed in human brain microvessel endothelial cells following oxygen-glucose deprivation and mCRP (but not column purified nCRP) associated with the endothelial cell surface, and was angiogenic to vascular endothelial cells, stimulating migration and tube formation in matrigel more strongly than fibroblast growth factor-2. The mechanism of signal transduction was not through the CD16 receptor. Western blotting showed that mCRP stimulated phosphorylation of the key down-stream mitogenic signalling protein ERK1/2. Pharmacological inhibition of ERK1/2 phosphorylation blocked the angiogenic effects of mCRP. We propose that mCRP may contribute to the neovascularization process and because of its abundant presence, be important in modulating angiogenesis in both acute stroke and later during neuro-recovery.
    Brain Pathology 02/2009; 20(1):151-65. · 4.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Angiogenesis correlates with patient survival following acute ischaemic stroke, and survival of neurons is greatest in tissue undergoing angiogenesis. Angiogenesis is critical for the development of new microvessels and leads to re-formation of collateral circulation, reperfusion, enhanced neuronal survival and improved recovery. Here, we have isolated active (CD105/Flt-1 positive) and inactive (CD105/Flt-1 minus (n=5) micro-vessel rich-regions from stroke-affected and contralateral tissue of patients using laser-capture micro-dissection. Areas were compared for pro- and anti-angiogenic gene expression using targeted TaqMan microfluidity cards containing 46 genes and real-time PCR. Further analysis of key gene de-regulation was performed by immunohistochemistry to define localization and expression patterns of identified markers and de novo synthesis by human brain microvessel endothelial cells (HBMEC) was examined following oxygen-glucose deprivation (OGD). Our data revealed that seven pro-angiogenic genes were notably up-regulated in CD105 positive microvessel rich regions. These were, beta-catenin, neural cell adhesion molecule (NRCAM), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), hepatocyte growth factor-alpha (HGF-alpha), monocyte chemottractant protein-1 (MCP-1) and and Tie-2 as well as c-kit. Immunohistochemistry demonstrated strong staining of MMP-2, HGF-alpha, MCP-1 and Tie-2 in stroke-associated regions of active remodeling in association with CD105 positive staining. In vitro, OGD stimulated production of Tie-2, MCP-1 and MMP-2 in HBMEC, demonstrated a de novo response to hypoxia. In this work we have identified concurrent activation of key angiogenic molecules associated with endothelial cell migration, differentiation and tube-formation, vessel stabilization and stem cell homing mechanisms in areas of revascularization. Therapeutic stimulation of these processes in all areas of damaged tissue might improve morbidity and mortality from stroke.
    BMC Genomics 02/2009; 10:113. · 4.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have demonstrated that expression of CD105 is a sensitive marker and indicator of endothelial cell/microvessel activation and proliferation in aggressive solid tumour growth and atherosclerotic plaque lesions. Since intimal neovascularization contributes significantly to subsequent plaque instability, haemorrhage and rupture. We have used immunohistochemical analysis to investigate the expression of CD105-positive vessels in both large (carotid) and medium calibre (coronary and middle cerebral artery, MCAs) diseased vessels in an attempt to identify any correlation with plaque growth, stage and complication/type. Here we show, that carotid arteries expressed intimal neovascularization associated with CD105-positive endothelial cells, concomitant with increased inflammation in early stage lesions, preatheroma (I-III) whilst they were not present in coronary plaques of the same grade. Some of these CD105-positive neovessels were immature, thin walled and without smooth muscle cell coverage making them more prone to haemorrhage and rupture. In high-grade lesions, neovessel proliferation was similar in both arterial types and significantly higher numbers of CD105-positive vasa vasorum were associated with plaque regions in coronary arteries. In contrast, although the MCAs exhibited expanded intimas and established plaques, there were very few CD105 positive neovessels. Our results show that CD105 is a useful marker of angiogenesis within adventitial and intimal vessels and suggest the existence of significant differences in the pathological development of atherosclerosis in separate vascular beds which may have important consequences when considering management and treatment of this disease.
    Journal of Angiogenesis Research 01/2009; 1:6.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Native C-reactive protein (nCRP) is a soluble acute phase reactant whose expression in the vascular wall; in particular, in reactive plaque regions, and circulating levels increase in patients with inflammatory disease. We have recently demonstrated a specific role for the insoluble, monomeric form of CRP (mCRP) in direct stimulation of an-giogenesis and therefore decided to investigate its expression in carotid adventitial vasa vasorum and plaque intimal neovessels to determine if it could be involved in the development of unstable plaque lesions. Methods: We have used immunohistochemistry to examine the expression of both mCRP and nCRP in a series of carotid arterial plaques obtained at transplant (n=20) and employed double immunoflourescent labelling to identify any associa-tion of CRP with active-CD105-positive microvessels. Results: Using characterised and specific antibodies we have identified strong expression of mCRP in adventitial vasa vasorum and angiogenic neovessels from unstable regions of complicated carotid plaques. mCRP was also found to be as-sociated with infiltrating macrophages in inflammatory regions but infrequently with vascular smooth muscle cells. nCRP was expressed much more weakly and only in some regions rich in inflammatory cells. Many of the mCRP-positive ves-sels also stained positive for CD105 suggesting they were actively involved in the process of angiogenesis. Conclusions: Based on our previously published observations of the highly angiogenic nature of mCRP in vitro, we hy-pothesise that mCRP is intimately involved in promotion of neovascularization and possibly, subsequent destabilization of atherosclerotic plaques and could be considered as a possible target for therapeutic manipulation of angiogenesis.
    The Open Circulation & Vascular Journal 01/2009; 2:23-29.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Formation of haemorrhagic neovessels in the intima of developing atherosclerotic plaques is thought to significantly contribute to plaque instability resulting in thrombosis. C-reactive protein (CRP) is an acute phase reactant whose expression in the vascular wall, in particular, in reactive plaque regions, and circulating levels increase in patients at high risk of cardiovascular events. Although CRP is known to induce a pro-inflammatory phenotype in endothelial cells (EC) a direct role on modulation of angiogenesis has not been established. Here, we show that CRP is a powerful inducer of angiogenesis in bovine aortic EC (BAEC) and human coronary artery EC (HCAEC). CRP, at concentrations corresponding to moderate/high risk (1-5 microg/ml), induced a significant increase in proliferation, migration and tube-like structure formation in vitro and stimulated blood vessel formation in the chick chorioallantoic membrane assay (CAM). CRP treated with detoxi-gel columns retained such effects. Western blotting showed that CRP increased activation of early response kinase-1/2 (ERK1/2), a key protein involved in EC mitogenesis. Furthermore, using TaqMan Low-density Arrays we identified key pro-angiogenic genes induced by CRP among them were vascular endothelial cell growth factor receptor-2 (VEGFR2/KDR), platelet-derived growth factor (PDGF-BB), notch family transcription factors (Notch1 and Notch3), cysteine-rich angiogenic inducer 61 (CYR61/CCN1) and inhibitor of DNA binding/differentiation-1 (ID1). This data suggests a role for CRP in direct stimulation of angiogenesis and therefore may be a mediator of neovessel formation in the intima of vulnerable plaques.
    BMC Cell Biology 10/2008; 9:47. · 2.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Normal cellular prion protein (PrP(C)) has multiple functions but its role in the development of atherosclerosis has not been studied. Our pilot microarray data showed increased expression of PrP(C) in tissue samples of complicated carotid lesions. Therefore in this study, we aimed to investigate its localisation within atherosclerotic arteries and its concentration in patient plasma. PrP(C) expression was examined using an enzyme immunometric assay (EIA) in plasma from patients undergoing endarterectomy. Carotid specimens and control vascular transplants were studied for PrP(C) and CD105 (endoglin, a marker of active vessels) expression by immunohistochemistry and real-time PCR. Patients with carotid disease had higher levels of plasma PrP(C) than the control group [4.35 ng/ml (n = 22; 3.1-5.3) vs. 1.95 ng/ml (n = 21; 1.1-2.5), P < 0.001]. Furthermore, CD105-positive plaques had higher PrP(C) expression which colocalized with CD105 in neovessels. There was a significant correlation between mRNA expression of PrP(C) and CD105 in tested plaques (P < 0.001; r = 0.7) supporting our immunohistochemical findings. We conclude that PrP(C) is expressed in carotid specimens and may be associated with neovessel growth or survival in these plaques. Our results suggest a role for PrP(C) in modulating neovessel formation in complicated plaques.
    Acta Neuropathologica 09/2008; 116(5):537-45. · 9.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background C-reactive protein (CRP) is an inflammatory and powerful marker of future vascular events. Recently, it has been proposed as a mediator molecule of atherosclerotic disease due to its multiple proatherogenic effects and its presence in atherosclerotic plaques. Material and methods CRP expression was analyzed by real time polymerase chain reaction (PCR) in advanced carotid plaques. Furthermore, protein expression was analyzed by immunohistochemistry in carotid atherosclerotic lesions obtained by endarterectomy and in carotid samples in different phases of progression. Results Analysis by real time PCR showed significantly higher levels of CRP in ulcerated non-complicated lesions as compared to complicated ulcerated lesions (p = 0.001) or fibrous lesions (p = 0.01). An immunohistochemistry assay for CRP showed that in advanced lesions, mainly infiltrated inflammatory cells and new vessels were stained. In contrast, no CRP staining was observed in early lesions and carotid artery controls. Conclusion CRP expression in carotid atherosclerotic lesions is induced in moderated and advanced stages of plaque progression, suggesting a possible role of this molecule in inflammation and neovascularization and triggering atherothrombotic complications.
    Clínica e Investigación en Arteriosclerosis. 06/2008; 20(3).
  • [Show abstract] [Hide abstract]
    ABSTRACT: C-reactive protein (CRP), an inflammatory marker, has been identified as a likely predictor of the risk of a future stroke. In clinical settings, it has been consistently observed that higher concentrations of CRP are associated with larger brain infarcts and worst neurologic outcome. However, there is still controversy over the degree of risk conferred by elevated CRP concentrations. CRP, like many other hemostatic factors, is an acute-phase protein and, therefore, it is not always clear whether its association with cerebrovascular disease reflects its contribution to atherothrombosis, its acute-phase condition, or both. Whether a reduction of CRP levels could be beneficial to stroke patients remains to be clarified. More studies are needed before CRP becomes a routine part of the evaluation of stroke patients.
    Current Cardiology Reports 03/2008; 10(1):25-30.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hypoxia, angiogenesis and inflammation leads to plaque progression and remodelling and may significantly contribute towards plaque rupture and subsequent cerebrovascular events. Our aim was to study, markers of hypoxia and inflammation previously identified by microarray analysis, in atherosclerotic carotid arteries with low to moderate stenosis. We hoped to describe different cellular populations expressing the studied markers. The location of selected inflammatory molecules obtained as vascular transplants from organ donors were analysed by immunohistochemistry with monoclonal and polyclonal antibodies. Paraffin-embedded sections were cut and probed with antibodies recognizing active B and T-lymphocytes (CD30), hypoxia-inducible factor-1alpha, endoglin (CD105), Interleukin-6 and C-reactive protein. We observed a notable overexpression of HIF-1alpha in inflammatory and hypoxic areas of carotid arteries in all types of lesions from type II-V taken from the patients with carotid stenosis less than 50%. This suggests that HIF-1alpha may have a putative role in atherosclerosis progression and angiogenesis. Dynamic changes in the non-occluding plaques may explain some of the clinical events in patients with low to moderate carotid stenosis.
    Frontiers in Bioscience 02/2008; 13:6483-90. · 3.29 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have shown that changes in expression of the glycosaminoglycan, hyaluronan (HA) were associated with erosion in areas of post-mortem coronary artery liable to rupture. Angiogenesis is an important feature of ulcerating haemorrhagic plaques prone to rupture. HA is a glycosaminoglycan known to possess potent angiogenic properties on metabolism to oligosaccharides of HA (o-HA) in the presence of hyaluronidase (HYAL) enzymes. In this study, we have examined HA receptor and HYAL enzyme expression in a series of carotid artery specimens used as vascular transplants and exhibiting various stages of atherosclerotic lesions as determined by anatomo-pathology. Our results demonstrated dramatically increased expression of HYAL-1 in regions of inflammation associated with complicated plaques. Receptor for HA-mediated motility (RHAMM), which is known to be important in transducing angiogenic signals in vascular endothelium, was strongly expressed on intimal blood vessels from complicated lesions but almost absent from other regions including adventitial vessels. Metabolism of HA, together with up-regulation of RHAMM in complicated plaque lesions might be partly responsible for over-production of leaky neovessels and predisposition to plaque rupture.
    Biomarker insights 02/2008; 2:361-7.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Carotid atherosclerosis is a leading cause of cerebrovascular events. The control of cardiovascular risk factors, i.e. tobacco smoking, alcohol abuse, hypertension, dyslipidemia, diabetes and obesity proved to reduce number of fatal and non-fatal strokes but failed to prevent important number of them. Screening for biomarkers in individuals at high risk of symptomatic vascular disease helped to identify some of them. However, as disease is by its nature multifocal, global testing for biomarkers may have limited practical application. New imaging techniques, including direct visualization of artery metabolism, by 18-FDG-PET, has brought new tools to study local atherosclerosis progression and individual plaque metabolic activity. Advances in molecular biology helped to identify inflammatory genes and its strong link to angiogenesis. The later, is thought to play a key role in the transformation to unstable plaque. Studies of the complex role that plays angiogenesis in plaque development will help in future to design effective therapies addressed at the individual cell level. The purpose of the review is to bring new insights into complicated pathophysiology of carotid atherosclerosis.
    Frontiers in Bioscience 02/2008; 13:6472-82. · 3.29 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cellular Prion Protein (PrPc) is a ubiquitous glycoprotein present on the surface of endothelial cells. Resting vascular endothelial cells show minimum expression of PrPc and can constitutively release PrPc. PrPc participates in cell survival, differentiation and angiogenesis. During development, neonatal brain endothelial cells transiently express PrPc. Our group recently reported upregulation of PrPc in microvessels from ischemic brain regions in stroke patients. Ischemia/hypoxia induces PrPc expression through the activation of extracellular signal-regulated kinase (ERK). All these data suggest that PrPc plays an important role in angiogenic responses. In addition, PrPc participates in cellular function in the central nervous system, since PrPc is also highly expressed in neurons. PrPc binds copper, suggesting a role in copper metabolism. PrPc also protects cells against oxidative stress and it seems to be involved in neuroprotection. Several studies have demonstrated that PrPc prevents cells from apoptosis and subsequent tissue damage. Moreover, PrPc plays an important role in the immune response. Here, we review the multiple functions of PrPc with a special attention to its recently reported role in angiogenesis.
    Frontiers in Bioscience 02/2008; 13:6491-500. · 3.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tissue factor (TF) expression is increased in inflammatory atherosclerotic plaques and has been related to plaque thrombogenicity. Blood-borne TF activity seems to contribute to a procoagulant state in patients with vascular risk factors. The aim of this study was to assess whether the expression of TF in carotid plaques from patients undergoing carotid endarterectomy (CEA) or/and blood-borne ('circulating') TF activity could predict future vascular complications. A total of 105 consecutive patients (85 male and 20 female aged 61-77 years)undergoing CEA for high-grade internal carotid artery were included in the study. Carotid artery specimens were classified into active (n = 52; rich in inflammatory cells) and nonactive plaques (n = 53; poor in inflammatory cells or fibrous). TF mRNA levels in carotid plaques were assessed by real-time PCR (TaqMan Low-Density Arrays) and TF protein levels by Western blot. Blood-borne TF activity and other biochemical parameters, including low-density lipoprotein cholesterol (LDLc) levels and high-sensitivity C-reactive protein, were measured prior to surgery. Patients were followed up for 1 year and vascular and nonvascular complications were scored. TF expression was higher in active CEA plaques. Patients with active CEA plaques exhibited higher plasma LDLc levels (3.6 +/- 0.7 vs. 2.1 +/- 1 mM, p < 0.05) that positively correlated with plaque TF mRNA levels (p = 0.0125; r = 0.9). Blood-borne TF activity did not correlate with plasma LDLc levels and was unrelated to the anatomo-pathological characteristic of the CEA plaques (thrombosis, rupture, inflammation, lipid core, necrosis or calcification). Circulating TF activity predicted vascular complications at 1 year, including fatal (OR, 1.18; 95% CI, 0.6-2.2, p < 0.01) and nonfatal ischemic stroke (OR, 1.22; 95% CI, 0.5-2.0, p < 0.05) and symptomatic peripheral vascular disease (OR, 1.48; 95% CI, 0.4-2.6, p < 0.005). Blood-borne TF activity prior to CEA but not local TF expression or plasma LDLc levels predict cerebrovascular and peripheral vascular disease events at 1 year in elderly patients subjected to CEA for high-grade carotid stenosis.
    Cerebrovascular Diseases 01/2008; 25(1-2):32-9. · 2.81 Impact Factor
  • Atherosclerosis Supplements - ATHEROSCLER SUPPL. 01/2008; 9(1):67-67.
  • [Show abstract] [Hide abstract]
    ABSTRACT: C-reactive protein (CRP), an inflammatory marker, has been identified as a likely predictor of the risk of a future stroke. In clinical settings, it has been consistently observed that higher concentrations of CRP are associated with larger brain infarcts and worst neurologic outcome. However, there is still controversy over the degree of risk conferred by elevated CRP concentrations. CRP, like many other hemostatic factors, is an acute-phase protein and, therefore, it is not always clear whether its association with cerebrovascular disease reflects its contribution to atherothrombosis, its acute-phase condition, or both. Whether a reduction of CRP levels could be beneficial to stroke patients remains to be clarified. More studies are needed before CRP becomes a routine part of the evaluation of stroke patients.
    Current Cardiology Reports 12/2007; 10(1):25-30.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Inflammation is receiving increased attention as a cause of atherosclerosis and stroke. Several inflammatory biomarkers, and particularly high-sensitivity C-reactive protein (hsCRP), have been identified as likely predictors of the risk of a future stroke. In clinical settings, it has been consistently observed that higher concentrations of CRP are associated with larger brain infarcts, stroke severity, neurologic disability, and future vascular events. However, there is still controversy over the degree of risk conferred by elevated CRP concentrations. Some studies reported that the predictive value of CRP is moderate compared with classical risk factors and is only weakly related to cardiovascular damage after adjustment for traditional cardiovascular risk factors. CRP like many other hemostatic factors is an acute-phase protein and, therefore, it is not always clear whether its association with cerebrovascular disease reflects its contribution to atherothrombosis, its acute-phase condition, or both. Furthermore, the value of single measurements of CRP in patients with concurrent infection or other inflammatory conditions has not been established and reported data should be interpreted cautiously. Several drugs, especially hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), have been demonstrated to reduce hsCRP levels independently of their effects on plasma cholesterol. Recently, emerging therapies have been aimed at the control of blood pressure and inflammation in stroke patients. Whether a reduction of hsCRP levels could be beneficial to stroke patients remains to be clarified, and it is also unclear whether other drugs may be useful to lower hsCRP levels. More studies are needed before hsCRP becomes a routine part of the evaluation of stroke patients. This should also prompt the search for new agents directly blocking CRP actions.
    Current Treatment Options in Cardiovascular Medicine 07/2007; 9(3):229-35.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The physiologic properties of the normal cellular prion protein (PrP(C)) have not been established fully, although recent evidence showed its upregulation in cerebral ischaemia. Using patients, animal models, and in vitro studies we aimed to identify in detail the expression and localization of PrP(C) in ischemic stroke. Patients in acute phase of ischaemic stroke had increased plasma levels of circulating PrP(C) as compared to healthy age- and gender-matched controls (3.1 +/- 1.4 vs. 1.9 +/- 0.7 ng/ml, P = 0.002). Immunohistochemistry showed increased expression of PrP(C) in the soma of peri-infarcted neurones as well as in the endothelial cells (EC) of micro-vessels and inflammatory cells in peri-infarcted brain tissue from patients who survived for 2-34 days after an initial stroke. The same pattern was repeated 1-48 hr after MCAO. RT-PCR showed increased gene expression of PrP(C) by human foetal neurons (HFN) after 12 hr of oxygen glucose deprivation (OGD), which remained increased after 24 hr reperfusion. Western blotting confirmed that protein expression was similarly upregulated, and fluorescent labeling showed a notable increase in peri-nuclear and axonal PrP(C) staining intensity. Increased plasma PrP(C) seems to reflect endogenous expression in acute stroke-affected brain tissue. Increased cellular expression in peri-infarcted regions may influence hypoxia-induced cell damage, although the effects on EC survival and angiogenesis remain to be elucidated.
    Journal of Neuroscience Research 03/2007; 85(3):602-11. · 2.97 Impact Factor

Publication Stats

287 Citations
56.17 Total Impact Points

Institutions

  • 2009–2012
    • Hospital Universitari Mutua de Terrassa
      Terrassa, Catalonia, Spain
  • 2008–2009
    • Hospital de la Santa Creu i Sant Pau
      Barcino, Catalonia, Spain
  • 2007–2009
    • Manchester Metropolitan University
      • School of Healthcare Science
      Manchester, England, United Kingdom
  • 2006–2008
    • Hospital Universitari de Bellvitge
      • Department of Neurology
      l'Hospitalet de Llobregat, Catalonia, Spain