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Papers by Ulf Hedin

Atherosclerosis

BACKGROUND AND AIMS Genome-wide association studies (GWAS) identified a coronary artery disease (... more BACKGROUND AND AIMS Genome-wide association studies (GWAS) identified a coronary artery disease (CAD) risk locus on 13.q34 tagged by rs61969072 (T/G). This variant lies in an intergenic region, proximal to ING1, CARKD and CARS2 but its causal relationship to CAD is unknown. METHODS AND RESULTS We first demonstrated that rs61969072 and tightly linked single nucleotide polymorphisms (SNPs) associate with CARS2 but not ING1 or CARKD expression in carotid endarterectomy samples, with reduced CARS2 abundance in carriers of the CAD risk allele (G). THP-1 monocytes were differentiated and polarized to proinflammatory (M1) and anti-inflammatory (M2) macrophages. CARS2 gene expression decreased in M1 and increased in M2 macrophages, consistent with a role for CARS2 in inflammation. Gene expression profiling revealed an increase in pro-inflammatory markers in response to CARS2 siRNA knockdown in THP-1 derived macrophages, accompanied by an increased abundance of inflammatory cytokines in the cell supernatant. Functional enrichment analysis of impacted transcripts identified the anti-inflammatory IL10 signalling pathway. Western blot analysis of CARS2 silenced macrophages revealed reduced STAT3 phosphorylation in response to IL-10 and increased expression of LPS-induced genes that are repressed by IL-10, indicating a role for CARS2 in anti-inflammatory signalling. Finally, to simulate vessel wall conditions, macrophages, and smooth muscle cells (SMC) were maintained in co-culture. Significantly, CARS2 silencing in macrophages altered the SMC phenotype, decreasing expression of contractile genes and increasing expression of inflammatory genes. CONCLUSIONS These data highlight a novel anti-inflammatory novel role for CARS2 in human macrophages and SMCs that may underlie the protective effect of a common GWAS-identified variant.

Arteriosclerosis, Thrombosis, and Vascular Biology, 2015

Proprotein convertases (PCSKs) are conserved among species and involved in processing of MMPs and... more Proprotein convertases (PCSKs) are conserved among species and involved in processing of MMPs and growth factors, but poorly characterised in atherosclerosis. Previously we demonstrated upregulation of PCSK6 in a large cohort of plaques from symptomatic vs. asymptomatic patients. This protease localized to smooth muscle cells (SMCs) and showed a positive correlation to markers of inflammation, extracellular matrix remodeling and cytokines in plaques. Here we aimed at elucidating its role in vascular development and disease. In zebrafish embryos PCSK6 localized to heart and vasculature and its ablation caused defective peripheral vascular patterning with cerebral and myocardial hemorrhage. Increased expression of PCSK6 in vascular pathologies was validated by microarrays from carotid plaques vs. undiseased arteries (n=32 patients, p<0.0001), abdominal (AAA, n=14, p<0.0001) and thoracic aortic aneurysms (TAA, n=244, p=0.012). By immunohistochemistry, PCSK6 localized mainly to SM...

Arteriosclerosis, Thrombosis, and Vascular Biology, 2014

Aim of the present study was to explore the role of miRNAs as potential regulators in patients wi... more Aim of the present study was to explore the role of miRNAs as potential regulators in patients with carotid artery stenosis and concordant vulnerable atherosclerotic plaques. Utilizing patient material from the Biobank of Karolinska Endarterectomies (BiKE), we were able to profile the regulation of miRNAs in patients with symptomatic vs. asymptomatic carotid stenosis undergoing carotid endarterectomy. A PCR-based miRNA array discovered 8 miRNAs (miRs-15b, -29c, -30c/d, -150, -191, -210 and -500) being substantially altered in symptomatic vs. asymptomatic patients. Next we investigated miRNA expression in 2 murine models of vascular injury and plaque vulnerability; balloon injury in Sprague-Dawley rats, and a newly-developed plaque rupture model in ApoE-/- mice, using incomplete ligation of the carotid artery with consecutive cuff injury to induce lesion rupture. In both models miR-210 was significantly repressed in response to vascular injury and plaque instability. In silico analys...

Arteriosclerosis, Thrombosis, and Vascular Biology, 2014

Introduction: Genome-wide association studies (GWAS) have identified chromosomal loci that affect... more Introduction: Genome-wide association studies (GWAS) have identified chromosomal loci that affect risk of coronary heart disease (CHD) independent of classical risk factors. One such association signal has been identified at 6q23.2 in both Caucasians and East Asians. The lead CHD-associated variant in this region, rs12190287, resides in the 3’ untranslated region of the basic-helix-loop-helix transcription factor, TCF21 , and is predicted to alter the seed binding site for miR-224. Allelic imbalance studies demonstrated significant imbalance of the TCF21 transcript that correlated with genotype at rs12190287. Hypothesis: We hypothesize that genetic variation at rs12190287 contributes to allele-specific TCF21 expression imbalance via miR-224 regulation, thus altering CHD risk. Methods and Results: Reporter assays in human coronary artery smooth muscle cells (HCASMC) showed that the disease-associated C allele is selectively targeted by miR-224, leading to reduced expression compared ...

Atherosclerosis Supplements, 2018

Scientific Reports, 2021

An amendment to this paper has been published and can be accessed via a link at the top of the pa... more An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Frontiers in Cell and Developmental Biology, 2021

Aging is accompanied by many physiological changes. These changes can progressively lead to many ... more Aging is accompanied by many physiological changes. These changes can progressively lead to many types of cardiovascular diseases. During this process blood vessels lose their ability to maintain vascular homeostasis, ultimately resulting in hypertension, stroke, or myocardial infarction. Increase in DNA damage is one of the hallmarks of aging and can be repaired by the DNA signaling and repair system. In our study we show that long non-coding RNA Aerrie (linc01013) contributes to the DNA signaling and repair mechanism. Silencing of Aerrie in endothelial cells impairs angiogenesis, migration, and barrier function. Aerrie associates with YBX1 and together they act as important factors in DNA damage signaling and repair. This study identifies Aerrie as a novel factor in genomic stability and as a binding partner of YBX1 in responding to DNA damage.

JVS-Vascular Science, 2021

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Cardiovascular Research, 2021

Aims Atherosclerotic cerebrovascular disease underlies the majority of ischaemic strokes and is ... more Aims Atherosclerotic cerebrovascular disease underlies the majority of ischaemic strokes and is a major cause of death and disability. While plaque burden is a predictor of adverse outcomes, plaque vulnerability is increasingly recognized as a driver of lesion rupture and risk for clinical events. Defining the molecular regulators of carotid instability could inform the development of new biomarkers and/or translational targets for at-risk individuals. Methods and results Using two independent human endarterectomy biobanks, we found that the understudied glycoprotein, chitinase 3 like 1 (CHI3L1), is up-regulated in patients with carotid disease compared to healthy controls. Further, CHI3L1 levels were found to stratify individuals based on symptomatology and histopathological evidence of an unstable fibrous cap. Gain- and loss-of-function studies in cultured human carotid artery smooth muscle cells (SMCs) showed that CHI3L1 prevents a number of maladaptive changes in that cell typ...

The Journal of Infectious Diseases, 2020

Multiple viruses are implicated in atherosclerosis, but the mechanisms by which they infect cells... more Multiple viruses are implicated in atherosclerosis, but the mechanisms by which they infect cells and contribute to plaque formation in arterial walls are not well understood. Based on reports showing the presence of enterovirus in atherosclerotic plaques we hypothesized that the coxsackievirus and adenovirus receptor (CXADR/CAR), although absent in normal arteries, could be induced during plaque formation. Large-scale microarray and mass spectrometric analyses revealed significant up-regulation of CXADR messenger RNA and protein levels in plaque-invested carotid arteries compared with control arteries. Macrophages were identified as a previously unknown cellular source of CXADR in human plaques and plaques from Ldr−/−Apob100/100 mice. CXADR was specifically associated with M1-polarized macrophages and foam cells and was experimentally induced during macrophage differentiation. Furthermore, it was significantly correlated with receptors for other viruses linked to atherosclerosis. T...

European Journal of Vascular and Endovascular Surgery, 2019

Introduction: The endovascular treatment with stenting in the femoro-popliteal arterial segment i... more Introduction: The endovascular treatment with stenting in the femoro-popliteal arterial segment is particularly challenging due to certain anatomical features and biomechanical forces to which it may be exposed. The purpose of this study is to report our 1-year results in term of efficacy of the dual stent (TIGRISÒ) in the femoro-popliteal region in patients with critical limb ischemia (CLI). Methods: We included patients classified as Rutherford grade !4 that required Tigris stent implantation in the femoro-popliteal region from January 2012 to January 2018 in one center. Two groups were analyzed: Group A, patients receiving Tigris stent in the superficial femoral artery [SFA] (n¼24) and Group B, in the popliteal artery (n¼21). The stenting indication in group A was primary stenting in 14 cases and angioplasty (ATP) failure in 10 cases. All cases included in group B were due to primary ATP failure (residual stenosis >50%, dissection or recoil). Technical success, primary patency, secondary patency and limb salvage are described for the entire cohort and both groups. The follow-up visits consisted of clinical examination and color-doppler ultrasound at 3, 6,12 months. Kaplan-Meyer analysis was used to estimate outcomes measures at 3,6 and 12 months. The groups were compared using the log-rank text. Results: Sixty-one TigrisÒ stent were implanted in 45 patients with mean age 74,67AE 1,6 years. More than 40% were classified as Rutherford V. Occlusion rate was 57,8%. The median follow-up was 12,02 months (range 3-72 months). For the entire series, technical success was 100%. Primary patency at 3 and 6 months was 91,1% and 84,4% at 12 months. Secondary patency at 3,6 and 12 months was, 95,6%, 93,3% and 86,7%, respectively. Limb salvage was 86,7% at 12-month analysis. The 2 groups were comparable for preoperative comorbidities. Patients in Group A had longer lesions (15,8mm vs 7,9mm, p¼0,044) requiring longer and more stents (124,2mm vs 82,9mm, p¼0,001). No difference in primary or secondary patency and limb salvage between both groups was found during follow-up. No stent fractures were reported. Conclusion: The TigrisÒ stent in the femoro-popliteal region has demonstrated high primary patency and limb salvage rate during the first year follow-up in complex cases such as those with CLI. No difference in patency rates regarding sector location of the stent was found. It is necessary to validate these results in the long term.

Atherosclerosis Supplements, 2009

Atherosclerosis Supplements, 2009

The Journal of Vascular Access, 2018

Introduction: Thrombosis is one of the most common complications of dialysis vascular access and ... more Introduction: Thrombosis is one of the most common complications of dialysis vascular access and is a significant source of morbidity and healthcare-associated costs. In this retrospective study, outcomes for surgical thrombectomy and thrombolysis after access thrombosis in patients with arteriovenous fistulas or prosthetic grafts (arteriovenous grafts) were analysed. Methods: All patients with a primary episode of dialysis access thrombosis between 2005 and 2013 were included which yielded 131 patients with 149 episodes of access thrombosis (108 arteriovenous grafts; 41 arteriovenous fistulas). In all, 18 patients had two separate accesses during the study. Patient demographics, access anatomy, surgical and radiological procedural data were recorded. Kaplan–Meier estimates and Poisson regression were used for statistical analysis of access patency. Results: In total, 107 underwent surgical thrombectomy and 42 were treated with catheter-directed thrombolytic infusion. Technical succ...

Journal of the American College of Cardiology, Jan 14, 2018

Cardiovascular complications are major clinical problems in type 2 diabetes mellitus (T2DM). The ... more Cardiovascular complications are major clinical problems in type 2 diabetes mellitus (T2DM). The authors previously demonstrated a crucial role of red blood cells (RBCs) in control of cardiac function through arginase-dependent regulation of nitric oxide export from RBCs. There is alteration of RBC function, as well as an increase in arginase activity, in T2DM. The authors hypothesized that RBCs from patients with T2DM induce endothelial dysfunction by up-regulation of arginase. RBCs were isolated from patients with T2DM and age-matched healthy subjects and were incubated with rat aortas or human internal mammary arteries from nondiabetic patients for vascular reactivity and biochemical studies. Arginase activity and arginase I protein expression were elevated in RBCs from patients with T2DM (T2DM RBCs) through an effect induced by reactive oxygen species (ROS). Co-incubation of arterial segments with T2DM RBCs, but not RBCs from age-matched healthy subjects, significantly impaired ...

Acta Chirurgica Belgica, 2004

Rupture of an abdominal aortic aneurysm (AAA) is an important cause of death, particularly in men... more Rupture of an abdominal aortic aneurysm (AAA) is an important cause of death, particularly in men over 60 years of age, where it constitutes 2% of all deaths (1). The only clinically robust parameter so far, determining the risk of rupture is the size of the aneurysm. The mechanical basis for this is the Law of La Place, which states that the wall tension is proportional to the diameter of a sphere. When applied to biological systems the inverse relationship to the thickness of the wall has been introduced into the equation (2). When evaluating the risk of rupture of AAA focus has mostly been on size (diameter) of the AAA but less on the capacity of its wall to withstand the strain that is proportional to size. Clearly aneurysm size is related to risk of rupture, but the risk is a product of both wall stress and the capacity of the wall to withstand it. The strength of the wall varies between aneurysms, that is why some small AAA rupture, whereas some large ones do not. The structural integrity of the aneurysm wall also varies within an individual aneurysm, probably because of different degrees of proteolytic degradation in various parts. One factor influencing the wall composition and possibly its capacity to withstand wall stress is the overlying thrombus. Here we will review the evidence for the influence of the thrombus on the cellular content and structural characteristics of the underlying aneurysm wall.

Atherosclerosis Supplements, 2006

Atherosclerosis

BACKGROUND AND AIMS Genome-wide association studies (GWAS) identified a coronary artery disease (... more BACKGROUND AND AIMS Genome-wide association studies (GWAS) identified a coronary artery disease (CAD) risk locus on 13.q34 tagged by rs61969072 (T/G). This variant lies in an intergenic region, proximal to ING1, CARKD and CARS2 but its causal relationship to CAD is unknown. METHODS AND RESULTS We first demonstrated that rs61969072 and tightly linked single nucleotide polymorphisms (SNPs) associate with CARS2 but not ING1 or CARKD expression in carotid endarterectomy samples, with reduced CARS2 abundance in carriers of the CAD risk allele (G). THP-1 monocytes were differentiated and polarized to proinflammatory (M1) and anti-inflammatory (M2) macrophages. CARS2 gene expression decreased in M1 and increased in M2 macrophages, consistent with a role for CARS2 in inflammation. Gene expression profiling revealed an increase in pro-inflammatory markers in response to CARS2 siRNA knockdown in THP-1 derived macrophages, accompanied by an increased abundance of inflammatory cytokines in the cell supernatant. Functional enrichment analysis of impacted transcripts identified the anti-inflammatory IL10 signalling pathway. Western blot analysis of CARS2 silenced macrophages revealed reduced STAT3 phosphorylation in response to IL-10 and increased expression of LPS-induced genes that are repressed by IL-10, indicating a role for CARS2 in anti-inflammatory signalling. Finally, to simulate vessel wall conditions, macrophages, and smooth muscle cells (SMC) were maintained in co-culture. Significantly, CARS2 silencing in macrophages altered the SMC phenotype, decreasing expression of contractile genes and increasing expression of inflammatory genes. CONCLUSIONS These data highlight a novel anti-inflammatory novel role for CARS2 in human macrophages and SMCs that may underlie the protective effect of a common GWAS-identified variant.

Arteriosclerosis, Thrombosis, and Vascular Biology, 2015

Proprotein convertases (PCSKs) are conserved among species and involved in processing of MMPs and... more Proprotein convertases (PCSKs) are conserved among species and involved in processing of MMPs and growth factors, but poorly characterised in atherosclerosis. Previously we demonstrated upregulation of PCSK6 in a large cohort of plaques from symptomatic vs. asymptomatic patients. This protease localized to smooth muscle cells (SMCs) and showed a positive correlation to markers of inflammation, extracellular matrix remodeling and cytokines in plaques. Here we aimed at elucidating its role in vascular development and disease. In zebrafish embryos PCSK6 localized to heart and vasculature and its ablation caused defective peripheral vascular patterning with cerebral and myocardial hemorrhage. Increased expression of PCSK6 in vascular pathologies was validated by microarrays from carotid plaques vs. undiseased arteries (n=32 patients, p<0.0001), abdominal (AAA, n=14, p<0.0001) and thoracic aortic aneurysms (TAA, n=244, p=0.012). By immunohistochemistry, PCSK6 localized mainly to SM...

Arteriosclerosis, Thrombosis, and Vascular Biology, 2014

Aim of the present study was to explore the role of miRNAs as potential regulators in patients wi... more Aim of the present study was to explore the role of miRNAs as potential regulators in patients with carotid artery stenosis and concordant vulnerable atherosclerotic plaques. Utilizing patient material from the Biobank of Karolinska Endarterectomies (BiKE), we were able to profile the regulation of miRNAs in patients with symptomatic vs. asymptomatic carotid stenosis undergoing carotid endarterectomy. A PCR-based miRNA array discovered 8 miRNAs (miRs-15b, -29c, -30c/d, -150, -191, -210 and -500) being substantially altered in symptomatic vs. asymptomatic patients. Next we investigated miRNA expression in 2 murine models of vascular injury and plaque vulnerability; balloon injury in Sprague-Dawley rats, and a newly-developed plaque rupture model in ApoE-/- mice, using incomplete ligation of the carotid artery with consecutive cuff injury to induce lesion rupture. In both models miR-210 was significantly repressed in response to vascular injury and plaque instability. In silico analys...

Arteriosclerosis, Thrombosis, and Vascular Biology, 2014

Introduction: Genome-wide association studies (GWAS) have identified chromosomal loci that affect... more Introduction: Genome-wide association studies (GWAS) have identified chromosomal loci that affect risk of coronary heart disease (CHD) independent of classical risk factors. One such association signal has been identified at 6q23.2 in both Caucasians and East Asians. The lead CHD-associated variant in this region, rs12190287, resides in the 3’ untranslated region of the basic-helix-loop-helix transcription factor, TCF21 , and is predicted to alter the seed binding site for miR-224. Allelic imbalance studies demonstrated significant imbalance of the TCF21 transcript that correlated with genotype at rs12190287. Hypothesis: We hypothesize that genetic variation at rs12190287 contributes to allele-specific TCF21 expression imbalance via miR-224 regulation, thus altering CHD risk. Methods and Results: Reporter assays in human coronary artery smooth muscle cells (HCASMC) showed that the disease-associated C allele is selectively targeted by miR-224, leading to reduced expression compared ...

Atherosclerosis Supplements, 2018

Scientific Reports, 2021

An amendment to this paper has been published and can be accessed via a link at the top of the pa... more An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Frontiers in Cell and Developmental Biology, 2021

Aging is accompanied by many physiological changes. These changes can progressively lead to many ... more Aging is accompanied by many physiological changes. These changes can progressively lead to many types of cardiovascular diseases. During this process blood vessels lose their ability to maintain vascular homeostasis, ultimately resulting in hypertension, stroke, or myocardial infarction. Increase in DNA damage is one of the hallmarks of aging and can be repaired by the DNA signaling and repair system. In our study we show that long non-coding RNA Aerrie (linc01013) contributes to the DNA signaling and repair mechanism. Silencing of Aerrie in endothelial cells impairs angiogenesis, migration, and barrier function. Aerrie associates with YBX1 and together they act as important factors in DNA damage signaling and repair. This study identifies Aerrie as a novel factor in genomic stability and as a binding partner of YBX1 in responding to DNA damage.

JVS-Vascular Science, 2021

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Cardiovascular Research, 2021

Aims Atherosclerotic cerebrovascular disease underlies the majority of ischaemic strokes and is ... more Aims Atherosclerotic cerebrovascular disease underlies the majority of ischaemic strokes and is a major cause of death and disability. While plaque burden is a predictor of adverse outcomes, plaque vulnerability is increasingly recognized as a driver of lesion rupture and risk for clinical events. Defining the molecular regulators of carotid instability could inform the development of new biomarkers and/or translational targets for at-risk individuals. Methods and results Using two independent human endarterectomy biobanks, we found that the understudied glycoprotein, chitinase 3 like 1 (CHI3L1), is up-regulated in patients with carotid disease compared to healthy controls. Further, CHI3L1 levels were found to stratify individuals based on symptomatology and histopathological evidence of an unstable fibrous cap. Gain- and loss-of-function studies in cultured human carotid artery smooth muscle cells (SMCs) showed that CHI3L1 prevents a number of maladaptive changes in that cell typ...

The Journal of Infectious Diseases, 2020

Multiple viruses are implicated in atherosclerosis, but the mechanisms by which they infect cells... more Multiple viruses are implicated in atherosclerosis, but the mechanisms by which they infect cells and contribute to plaque formation in arterial walls are not well understood. Based on reports showing the presence of enterovirus in atherosclerotic plaques we hypothesized that the coxsackievirus and adenovirus receptor (CXADR/CAR), although absent in normal arteries, could be induced during plaque formation. Large-scale microarray and mass spectrometric analyses revealed significant up-regulation of CXADR messenger RNA and protein levels in plaque-invested carotid arteries compared with control arteries. Macrophages were identified as a previously unknown cellular source of CXADR in human plaques and plaques from Ldr−/−Apob100/100 mice. CXADR was specifically associated with M1-polarized macrophages and foam cells and was experimentally induced during macrophage differentiation. Furthermore, it was significantly correlated with receptors for other viruses linked to atherosclerosis. T...

European Journal of Vascular and Endovascular Surgery, 2019

Introduction: The endovascular treatment with stenting in the femoro-popliteal arterial segment i... more Introduction: The endovascular treatment with stenting in the femoro-popliteal arterial segment is particularly challenging due to certain anatomical features and biomechanical forces to which it may be exposed. The purpose of this study is to report our 1-year results in term of efficacy of the dual stent (TIGRISÒ) in the femoro-popliteal region in patients with critical limb ischemia (CLI). Methods: We included patients classified as Rutherford grade !4 that required Tigris stent implantation in the femoro-popliteal region from January 2012 to January 2018 in one center. Two groups were analyzed: Group A, patients receiving Tigris stent in the superficial femoral artery [SFA] (n¼24) and Group B, in the popliteal artery (n¼21). The stenting indication in group A was primary stenting in 14 cases and angioplasty (ATP) failure in 10 cases. All cases included in group B were due to primary ATP failure (residual stenosis >50%, dissection or recoil). Technical success, primary patency, secondary patency and limb salvage are described for the entire cohort and both groups. The follow-up visits consisted of clinical examination and color-doppler ultrasound at 3, 6,12 months. Kaplan-Meyer analysis was used to estimate outcomes measures at 3,6 and 12 months. The groups were compared using the log-rank text. Results: Sixty-one TigrisÒ stent were implanted in 45 patients with mean age 74,67AE 1,6 years. More than 40% were classified as Rutherford V. Occlusion rate was 57,8%. The median follow-up was 12,02 months (range 3-72 months). For the entire series, technical success was 100%. Primary patency at 3 and 6 months was 91,1% and 84,4% at 12 months. Secondary patency at 3,6 and 12 months was, 95,6%, 93,3% and 86,7%, respectively. Limb salvage was 86,7% at 12-month analysis. The 2 groups were comparable for preoperative comorbidities. Patients in Group A had longer lesions (15,8mm vs 7,9mm, p¼0,044) requiring longer and more stents (124,2mm vs 82,9mm, p¼0,001). No difference in primary or secondary patency and limb salvage between both groups was found during follow-up. No stent fractures were reported. Conclusion: The TigrisÒ stent in the femoro-popliteal region has demonstrated high primary patency and limb salvage rate during the first year follow-up in complex cases such as those with CLI. No difference in patency rates regarding sector location of the stent was found. It is necessary to validate these results in the long term.

Atherosclerosis Supplements, 2009

Atherosclerosis Supplements, 2009

The Journal of Vascular Access, 2018

Introduction: Thrombosis is one of the most common complications of dialysis vascular access and ... more Introduction: Thrombosis is one of the most common complications of dialysis vascular access and is a significant source of morbidity and healthcare-associated costs. In this retrospective study, outcomes for surgical thrombectomy and thrombolysis after access thrombosis in patients with arteriovenous fistulas or prosthetic grafts (arteriovenous grafts) were analysed. Methods: All patients with a primary episode of dialysis access thrombosis between 2005 and 2013 were included which yielded 131 patients with 149 episodes of access thrombosis (108 arteriovenous grafts; 41 arteriovenous fistulas). In all, 18 patients had two separate accesses during the study. Patient demographics, access anatomy, surgical and radiological procedural data were recorded. Kaplan–Meier estimates and Poisson regression were used for statistical analysis of access patency. Results: In total, 107 underwent surgical thrombectomy and 42 were treated with catheter-directed thrombolytic infusion. Technical succ...

Journal of the American College of Cardiology, Jan 14, 2018

Cardiovascular complications are major clinical problems in type 2 diabetes mellitus (T2DM). The ... more Cardiovascular complications are major clinical problems in type 2 diabetes mellitus (T2DM). The authors previously demonstrated a crucial role of red blood cells (RBCs) in control of cardiac function through arginase-dependent regulation of nitric oxide export from RBCs. There is alteration of RBC function, as well as an increase in arginase activity, in T2DM. The authors hypothesized that RBCs from patients with T2DM induce endothelial dysfunction by up-regulation of arginase. RBCs were isolated from patients with T2DM and age-matched healthy subjects and were incubated with rat aortas or human internal mammary arteries from nondiabetic patients for vascular reactivity and biochemical studies. Arginase activity and arginase I protein expression were elevated in RBCs from patients with T2DM (T2DM RBCs) through an effect induced by reactive oxygen species (ROS). Co-incubation of arterial segments with T2DM RBCs, but not RBCs from age-matched healthy subjects, significantly impaired ...

Acta Chirurgica Belgica, 2004

Rupture of an abdominal aortic aneurysm (AAA) is an important cause of death, particularly in men... more Rupture of an abdominal aortic aneurysm (AAA) is an important cause of death, particularly in men over 60 years of age, where it constitutes 2% of all deaths (1). The only clinically robust parameter so far, determining the risk of rupture is the size of the aneurysm. The mechanical basis for this is the Law of La Place, which states that the wall tension is proportional to the diameter of a sphere. When applied to biological systems the inverse relationship to the thickness of the wall has been introduced into the equation (2). When evaluating the risk of rupture of AAA focus has mostly been on size (diameter) of the AAA but less on the capacity of its wall to withstand the strain that is proportional to size. Clearly aneurysm size is related to risk of rupture, but the risk is a product of both wall stress and the capacity of the wall to withstand it. The strength of the wall varies between aneurysms, that is why some small AAA rupture, whereas some large ones do not. The structural integrity of the aneurysm wall also varies within an individual aneurysm, probably because of different degrees of proteolytic degradation in various parts. One factor influencing the wall composition and possibly its capacity to withstand wall stress is the overlying thrombus. Here we will review the evidence for the influence of the thrombus on the cellular content and structural characteristics of the underlying aneurysm wall.

Atherosclerosis Supplements, 2006