25 results on '"Lindeman, Jan H.N."'
Search Results
2. Athero-occlusive Disease Appears to be Associated with Slower Abdominal Aortic Aneurysm Growth: An Exploratory Analysis of the TEDY Trial.
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Matthews, Evan O., Moxon, Joseph V., Singh, Tejas P., Thanigaimani, Shivshankar, Jones, Rhondda E., Gasser, Thomas C., Fitridge, Robert, Lindeman, Jan H.N., Dalman, Ronald L., and Golledge, Jonathan
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The role of atherosclerosis in abdominal aortic aneurysm (AAA) pathogenesis is controversial. The aim of this study was to compare AAA growth in patients who did and did not have concurrent athero-occlusive disease (AOD). Patients with an AAA measuring 35 – 49 mm in maximum diameter were recruited as part of the TElmisartan in the management of abdominal aortic aneurysm (TEDY) trial. TEDY participants who had infrarenal aortic volume and orthogonal diameter assessed by computed tomography at entry and at least one other time point during the trial (12 and/or 24 months) were included. AOD was defined by prior diagnoses of coronary heart disease, stroke, or peripheral arterial disease or an ankle brachial pressure index < 0.90. The increase in AAA volume and diameter from entry for participants who did and did not have AOD was assessed using linear mixed effects models; 131 of the 210 participants recruited to TEDY were included. In an unadjusted analysis, the mean (95% confidence interval) annual increases in AAA volume and diameter for participants with AOD were 3.26 (0.82 – 5.70) cm
3 and 0.70 (0.19 – 1.22) mm slower than those without AOD, p =.008 and.007 respectively. The association between AOD and significantly slower AAA growth was maintained after adjusting for risk factors and medications, significantly unequally distributed between participants with and without an AOD diagnosis. In an exploratory analysis of a selective cohort from the TEDY trial, AOD was associated with slower AAA growth. Validation of these findings in other cohorts is needed. [ABSTRACT FROM AUTHOR]- Published
- 2022
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3. Plaque Evaluation by Ultrasound and Transcriptomics Reveals BCLAF1 as a Regulator of Smooth Muscle Cell Lipid Transdifferentiation in Atherosclerosis
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Rykaczewska, Urszula, Zhao, Quanyi, Saliba-Gustafsson, Peter, Lengquist, Mariette, Kronqvist, Malin, Bergman, Otto, Huang, Zhiqiang, Lund, Kent, Waden, Katarina, Pons Vila, Zara, Caidahl, Kenneth, Skogsberg, Josefin, Vukojevic, Vladana, Lindeman, Jan H.N., Roy, Joy, Hansson, Göran K., Treuter, Eckardt, Leeper, Nicholas J., Eriksson, Per, Ehrenborg, Ewa, Razuvaev, Anton, Hedin, Ulf, and Matic, Ljubica
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- 2022
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4. Towards Patient Centred Outcomes for Elective Abdominal Aortic Aneurysm Repair: A Scoping Review of Quality of Life Scales.
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Bulder, Ruth M.A., Hamming, Jaap F., van Schaik, Jan, and Lindeman, Jan H.N.
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In order to better incorporate the patient's perspective in medical decision making, core outcome sets (COS) are being defined. In the field of abdominal aortic aneurysm (AAA), efforts to capture the patient's perspective focus on generic quantitative quality of life (QoL) scales. The question arises whether these quantitative scales adequately reflect the patient's perspective on QoL, and whether they can be included in the QoL aspect of COS. A scoping review of QoL assessment in the context of elective AAA repair was undertaken. PubMed, Embase, Web of Science, and the Cochrane Library. A scoping review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Articles reporting QoL assessment in the context of elective AAA repair were identified. Quantitative studies (i.e., traditional QoL scales) were aligned (triangulation approach) with qualitative studies (i.e., patient perspective) to identify parallels and discrepancies. Mean Short Form 36 item survey (SF-36) scores were pooled using a random effects model to evaluate sensitivity to change. Thirty-three studies were identified, of which 29 (88%) were quantitative and four (12%) qualitative. The 33 studies reported a total of 54 quantitative QoL scales; the most frequently used were the generic SF-36 (16 studies) and five dimension EuroQol (EQ-5D; eight studies). Aneurysm specific scales were reported by one study. The generic quantitative scales showed poor alignment with the patient's perspective. The aneurysm specific scales better aligned but missed "concerns regarding symptoms" and "the impact of possible outcomes/complications". "Self control and decision making", which was brought forward by patients in qualitative studies, was not captured in any of the current scales. There is no established tool that fully captures all aspects of the patient's perspective appropriate for a COS for elective AAA repair. In order to fulfil the need for a COS for the management of
, AAA disease, a more comprehensive overview of the patient's perspective is required. [ABSTRACT FROM AUTHOR]- Published
- 2021
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5. Cytoskeletal protein degradation in brain death donor kidneys associates with adverse posttransplant outcomes
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Vaughan, Rebecca H., Kresse, Jean-Claude, Farmer, Louise K., Thézénas, Marie L., Kessler, Benedikt M., Lindeman, Jan H.N., Sharples, Edward J., Welsh, Gavin I., Nørregaard, Rikke, Ploeg, Rutger J., and Kaisar, Maria
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In brain death, cerebral injury contributes to systemic biological dysregulation, causing significant cellular stress in donor kidneys adversely impacting the quality of grafts. Here, we hypothesized that donation after brain death (DBD) kidneys undergo proteolytic processes that may deem grafts susceptible to posttransplant dysfunction. Using mass spectrometry and immunoblotting, we mapped degradation profiles of cytoskeletal proteins in deceased and living donor kidney biopsies. We found that key cytoskeletal proteins in DBD kidneys were proteolytically cleaved, generating peptide fragments, predominantly in grafts with suboptimal posttransplant function. Interestingly, α-actinin-4 and talin-1 proteolytic fragments were detected in brain death but not in circulatory death or living donor kidneys with similar donor characteristics. As talin-1 is a specific proteolytic target of calpain-1, we investigated a potential trigger of calpain activation and talin-1 degradation using human ex vivo precision-cut kidney slices and in vitro podocytes. Notably, we showed that activation of calpain-1 by transforming growth factor-β generated proteolytic fragments of talin-1 that matched the degradation fragments detected in DBD preimplantation kidneys, also causing dysregulation of the actin cytoskeleton in human podocytes; events that were reversed by calpain-1 inhibition. Our data provide initial evidence that brain death donor kidneys are more susceptible to cytoskeletal protein degradation. Correlation to posttransplant outcomes may be established by future studies.
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- 2022
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6. Preclinical models versus clinical renal ischemia reperfusion injury: A systematic review based on metabolic signatures
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Lerink, Lente J.S., de Kok, Michèle J.C., Mulvey, John F., Le Dévédec, Sylvia E., Markovski, Alexander A., Wüst, Rob C.I., Alwayn, Ian P.J., Ploeg, Rutger J., Schaapherder, Alexander F.M., Bakker, Jaap A., and Lindeman, Jan H.N.
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Despite decennia of research and numerous successful interventions in the preclinical setting, renal ischemia reperfusion (IR) injury remains a major problem in clinical practice, pointing toward a translational gap. Recently, two clinical studies on renal IR injury (manifested either as acute kidney injury or as delayed graft function) identified metabolic derailment as a key driver of renal IR injury. It was reasoned that these unambiguous metabolic findings enable direct alignment of clinical with preclinical data, thereby providing the opportunity to elaborate potential translational hurdles between preclinical research and the clinical context. A systematic review of studies that reported metabolic data in the context of renal IR was performed according to the PRISMA guidelines. The search (December 2020) identified 35 heterogeneous preclinical studies. The applied methodologies were compared, and metabolic outcomes were semi-quantified and aligned with the clinical data. This review identifies profound methodological challenges, such as the definition of IR injury, the follow-up time, and sampling techniques, as well as shortcomings in the reported metabolic information. In light of these findings, recommendations are provided in order to improve the translatability of preclinical models of renal IR injury.
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- 2022
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7. Editor's Choice – A Systemic Evaluation of the Costs of Elective EVAR and Open Abdominal Aortic Aneurysm Repair Implies Cost Equivalence.
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Bulder, Ruth M.A., Eefting, Daniël, Vriens, Patrick W.H.E., van Tongeren, Robert B., Matsumura, Jon S., van den Hout, Wilbert B., Hamming, Jaap F., and Lindeman, Jan H.N.
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The suggested high costs of endovascular aneurysm repair (EVAR) hamper the choice of insurance companies and financial regulators for EVAR as the primary option for elective abdominal aortic aneurysm (AAA) repair. However, arguments used in this debate are impeded by time related aspects such as effect modification and the introduction of confounding by indication, and by asymmetric evaluation of outcomes. Therefore, a re-evaluation minimising the impact of these interferences was considered. A comparative analysis was performed evaluating a period of exclusive open repair (OR; 1998–2000) and a period of established EVAR (2010–2012). Data from four hospitals in The Netherlands were collected to estimate resource use. Actual costs were estimated by benchmark cost prices and a literature review. Costs are reported at 2019 prices. A break even approach, defining the costs for an endovascular device at which cost equivalence for EVAR and OR is achieved, was applied to cope with the large variation in endovascular device costs. One hundred and eighty-six patients who underwent elective AAA repair between 1998 and 2000 (OR period) and 195 patients between 2010 and 2012 (EVAR period) were compared. Cost equivalence for OR and EVAR was reached at a break even price for an endovascular device of €13 190. The main cost difference reflected the longer duration of hospital stay (ward and Intensive Care Unit) of OR (€11 644). Re-intervention rates were similar for OR (24.2%) and EVAR (24.6%) (p =.92). Cost equivalence for EVAR and OR occurs at a device cost of €13 000 for EVAR. Hence, for most routine repairs, EVAR is not costlier than OR until at least the five year follow up. [ABSTRACT FROM AUTHOR]
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- 2020
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8. The Differential Impact of Early Graft Dysfunction in Kidney Donation After Brain Death and After Circulatory Death: Insights from the Dutch National Transplant Registry
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Steenvoorden, Thei S., Evers, Lara, Vogt, Liffert, Rood, Janneke A.J., Kers, Jesper, Baas, Marije C., Christiaans, Maarten H.L., Lindeman, Jan H.N., Sanders, Jan-Stephan F., de Vries, Aiko P.J., van Zuilen, Arjan D., Bemelman, Frederike J., and Peters-Sengers, Hessel
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Kidneys donated after circulatory death (DCD) perform similarly to kidneys donated after brain death (DBD). However, the respective incidences of delayed graft function (DGF) differ. This questions the donor type-specific impact of early graft function on long-term outcome. Using competing risk and cox regression analysis, we compared death-censored graft loss between types of early graft function: DGF (temporary dialysis dependency started within seven days after transplantation), slow graft function (SGF, three-day plasma creatinine decline less than 10% per day), and immediate graft function (IGF). In 1061 DBD and 1605 DCD graft recipients (January 2014 until January 2023), graft survival was similar. DGF was associated with death-censored graft loss in DBD and DCD (adjusted hazard ratios [aHR]: DGF in DBD: 1.79 [1.04– 2.91], p = 0.027, DGF in DCD: 1.84 [1.18 – 2.87], p = 0.008; Reference: no DGF). SGF was associated with death-censored graft loss in DBD, but not significantly in DCD (aHR DBD: 2.82 (1.34 – 5.93), p = 0.007, and DCD: 1.54 (0.72 – 3.35), p = 0.262; Reference: IGF). Early graft dysfunction has a differential impact on graft outcome in DBD and DCD. The differences between DBD and DCD should be accounted for in research and the clinic.
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- 2024
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9. Red blood cells as oxygen carrier during normothermic machine perfusion of kidney grafts: Friend or foe?
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Arykbaeva, Asel S., Lerink, Lente J.S., Vos, Jaël, Engelse, Marten A., van Kooten, Cees, de Korte, Dirk, Lagerberg, Johan W.M., Klei, Thomas R.L., Mulder, Aat A., Minnee, Robert C., Ploeg, Rutger J., Moers, Cyril, Pol, Robert A., Alwayn, Ian P.J., de Vries, Dorottya K., and Lindeman, Jan H.N.
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Renal ex vivo normothermic machine perfusion (NMP) is under development as an assessment tool for high-risk kidney grafts and as a means of achieving more physiologically accurate organ preservation. On-going hemolysis has been reported during NMP, as this technique relies on red blood cells for oxygen delivery. In this study, we confirm the occurrence of progressive hemolysis during 6-hour kidney NMP. NMP-associated erythrostasis in the glomeruli and in peri-glomerular vascular networks points to an interaction between the red blood cells and the graft. Continuous hemolysis resulted in prooxidative changes in the perfusate, which could be quenched by addition of fresh frozen plasma. In a cell-based system, this hemolysis induced redox stress and exhibited toxic effects at high concentrations. These findings highlight the need for a more refined oxygen carrier in the context of renal NMP.
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- 2024
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10. pathophysiological concepts of ischemia reperfusion injury and normothermic, ex-vivo kidney
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Lindeman, Jan H.N. and Schaapherder, Alexander F.M.
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- 2024
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11. A registry-based rationale for discrete intervention thresholds for open and endovascular elective abdominal aortic aneurysm repair in female patients.
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Tomee, Stephanie M., Lijftogt, Niki, Vahl, Anco, Hamming, Jaap F., and Lindeman, Jan H.N.
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Objective An evidence-based consensus for a female-specific intervention threshold for abdominal aortic aneurysms (AAAs) is missing. This study aims to analyze sex-related differences in the epidemiology of ruptured AAA to establish an intervention threshold for women. Methods The Dutch Surgical Aneurysm Audit (DSAA) is a compulsory, nation-wide registry of AAA repairs in The Netherlands. All patients with emergency or elective AAA repair between January 1, 2013, and December 31, 2015, were included in the analysis. The main outcomes were age, sex, AAA diameter at time of rupture, and 30-day postoperative mortality. Results A total of 1561 ruptured AAA repairs (14.7% women) and 7063 cases of elective AAA repair (13.7% women) were included in the analysis. Women had significantly smaller mean ± standard deviation AAA diameter at time of rupture than men; 70.5 ± 14.4 mm and 78.6 ± 17.5 mm, respectively. In male patients, 8% of ruptures occurred at diameters below the 55 mm intervention threshold. The female equivalent of this eighth percentile is 52 mm. Female patients had significantly higher 30-day mortality after emergency repair, namely, 33% for women versus 24.2% for men, but were also significantly older, mean ± standard deviation age 76.7 ± 7.1 years and 73.9 ± 8.3 years for women and men, respectively. Correcting for age reduced the 30-day mortality risk for women after ruptured AAA repair from 1.53 (95% confidence interval, 1.14-2.04) to 1.27 (95% confidence interval, 0.92-1.73). Outcome after open elective repair was significantly worse for women compared with men, with a 30-day mortality of 7.97% 30 for women and 4.27% for men ( P < .01). Conclusions The equivalent of the 55-mm intervention threshold for elective endovascular AAA repair in men is 52 mm in women. The almost doubled mortality risk for elective open repair in women implies that the optimal point for open repair is at higher diameters, very possibly at least 55 mm. [ABSTRACT FROM AUTHOR]
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- 2018
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12. Hypothesis of the High Mortality of Female Patients Following Elective Open Abdominal Aortic Aneurysm Repair.
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Bulder, Ruth M.A., Tedjawirja, Victoria N., Hamming, Jaap F., Koelemay, Mark J., Balm, Ron, and Lindeman, Jan H.N.
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- 2022
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13. Wnt Signaling Pathway Inhibitor Sclerostin Inhibits Angiotensin II–Induced Aortic Aneurysm and Atherosclerosis
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Krishna, Smriti Murali, Seto, Sai-Wang, Jose, Roby J., Li, Jiaze, Morton, Susan K., Biros, Erik, Wang, Yutang, Nsengiyumva, Vianne, Lindeman, Jan H.N., Loots, Gabriela G., Rush, Catherine M., Craig, Jeffrey M., and Golledge, Jonathan
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Supplemental Digital Content is available in the text.
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- 2017
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14. Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis Is Associated With Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM
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Perisic Matic, Ljubica, Rykaczewska, Urszula, Razuvaev, Anton, Sabater-Lleal, Maria, Lengquist, Mariette, Miller, Clint L., Ericsson, Ida, Röhl, Samuel, Kronqvist, Malin, Aldi, Silvia, Magné, Joelle, Paloschi, Valentina, Vesterlund, Mattias, Li, Yuhuang, Jin, Hong, Diez, Maria Gonzalez, Roy, Joy, Baldassarre, Damiano, Veglia, Fabrizio, Humphries, Steve E., de Faire, Ulf, Tremoli, Elena, Odeberg, Jacob, Vukojević, Vladana, Lehtiö, Janne, Maegdefessel, Lars, Ehrenborg, Ewa, Paulsson-Berne, Gabrielle, Hansson, Göran K., Lindeman, Jan H.N., Eriksson, Per, Quertermous, Thomas, Hamsten, Anders, and Hedin, Ulf
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Supplemental Digital Content is available in the text.
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- 2016
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15. Defective postreperfusion metabolic recovery directly associates with incident delayed graft function
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Wijermars, Leonie G.M., Schaapherder, Alexander F., de Vries, Dorottya K., Verschuren, Lars, Wüst, Rob C.I., Kostidis, Sarantos, Mayboroda, Oleg A., Prins, Frans, Ringers, Jan, Bierau, Jörgen, Bakker, Jaap A., Kooistra, Teake, and Lindeman, Jan H.N.
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Delayed graft function (DGF) following kidney transplantation affects long-term graft function and survival and is considered a manifestation of ischemia reperfusion injury. Preclinical studies characterize metabolic defects resulting from mitochondrial damage as primary driver of ischemia reperfusion injury. In a comprehensive approach that included sequential establishment of postreperfusion arteriovenous concentration differences over the human graft, metabolomic and genomic analysis in tissue biopsies taken before and after reperfusion, we tested whether the preclinical observations translate to the context of clinical DGF. This report is based on sequential studies of 66 eligible patients of which 22 experienced DGF. Grafts with no DGF immediately recovered aerobic respiration as indicated by prompt cessation of lactate release following reperfusion. In contrast, grafts with DGF failed to recover aerobic respiration and showed persistent adenosine triphosphate catabolism indicated by a significant persistently low post reperfusion tissue glucose-lactate ratio and continued significant post-reperfusion lactate and hypoxanthine release (net arteriovenous difference for lactate and hypoxanthine at 30 minutes). The metabolic data for the group with DGF point to a persistent post reperfusion mitochondrial defect, confirmed by functional (respirometry) and morphological analyses. The archetypical mitochondrial stabilizing peptide SS-31 significantly preserved mitochondrial function in human kidney biopsies following simulated ischemia reperfusion. Thus, development of DGF is preceded by a profound post-reperfusion metabolic deficit resulting from severe mitochondrial damage. Strategies aimed at preventing DGF should be focused on safeguarding a minimally required post-reperfusion metabolic competence.
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- 2016
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16. The pathophysiology of abdominal aortic aneurysm growth: Corresponding and discordant inflammatory and proteolytic processes in abdominal aortic and popliteal artery aneurysms.
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Abdul-Hussien, Hazem, Hanemaaijer, Roeland, Kleemann, Robert, Verhaaren, Ben F.J., van Bockel, J. Hajo, and Lindeman, Jan H.N.
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PATHOLOGICAL physiology ,ABDOMINAL aortic aneurysms ,INFLAMMATION ,PROTEOLYSIS ,DISEASE progression ,NF-kappa B ,MESSENGER RNA ,INTERLEUKINS - Abstract
Objective: There is remarkable controversy over the processes driving abdominal aneurysm growth. The inherent limitations of animal and human studies hamper elucidation of the key inflammatory and proteolytic processes. Human data are largely derived from surgical specimens that typically reflect the final stages of the disease process and thus do not allow distinction between primary and secondary processes. Clear epidemiologic and genetic associations between abdominal aortic aneurysm (AAA) and popliteal artery aneurysms (PAA) suggest that that these two pathologies share common grounds. On this basis, we reasoned that information of corresponding and discordant processes in these aneurysms might provide critical clues on the processes that are crucial for aneurysm progression. Methods: Messenger RNA (semi-quantitative real-time polymerase chain reaction) and protein analysis (enzyme-linked immunosorbent assay, multiplex, Western blotting), and histology were performed on aneurysm wall samples obtained during elective PAA and AAA repair. Nonaneurysmal aorta tissue from organ donors was included as reference. Results: Messenger RNA and protein analysis showed that PAA and AAA are both characterized by a marked activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) proinflammatory transcription factors, and hyperexpression of interleukin (IL)-6 and IL-8. Discordant findings were found for other inflammatory markers such as interferon-γ, interferon-inducible protein 10, tumor necrosis factor-α, monocyte chemotactic protein-1, and macrophage inflammatory protein 1α and β, which were all lower in PAA. On the cellular level, both pathologies exhibited profuse infiltration of macrophages, neutrophils, and T-helper cells. Results for B cells, plasma cells, and cytotoxic T cells were discordant, with minimal infiltration of these cell types in PAA. Evaluation of protease expression and activation showed that both conditions are dominated by increased matrix metalloproteinase 8 and 9, and cathepsin K, L and S expression and activation. Conclusion: This explorative study characterizes degenerative aneurysmal disease general inflammatory conditions that are dominated by profound activation of the NF-κB and AP-1 pathways, hyperexpression of IL-6 and IL-8, and neutrophil involvement. Discordant findings for interferon γ, cytotoxic T cells, B cells, and plasma cells challenge a critical role for these factors in the process of aneurysm growth. Pharmaceutic strategies targeting the common components in AAA and PAA may prove effective for the stabilization of AAA. [Copyright &y& Elsevier]
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- 2010
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17. Doxycycline therapy for abdominal aneurysm: Improved proteolytic balance through reduced neutrophil content.
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Abdul-Hussien, Hazem, Hanemaaijer, Roeland, Verheijen, Jan H., van Bockel, J. Hajo, Geelkerken, Robert H., and Lindeman, Jan H.N.
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TREATMENT of abdominal aneurysms ,TETRACYCLINE ,PROTEOLYSIS ,NEUTROPHILS ,POLYMERASE chain reaction ,LABORATORY rodents ,CLINICAL trials ,IMMUNOHISTOCHEMISTRY - Abstract
Background: Matrix metalloproteinase-9 (MMP-9) is thought to play a central role in abdominal aortic aneurysm (AAA) initiation. Doxycycline, a tetracycline analogue, has direct MMP-9-inhibiting properties in vitro, and it effectively suppresses AAA development in rodents. Observed inhibition of AAA progression, and contradictory findings in human studies evaluating the effect of doxycycline therapy on aortic wall MMP-9, suggest that the effects of doxycycline extend beyond MMP-9 inhibition and that the effect may be dose-dependent. Methods: This clinical trial evaluated the effect of 2 weeks of low- (50 mg/d), medium- (100 mg/d), or high-dose (300 mg/d) doxycycline vs no medication in four groups of 15 patients undergoing elective AAA repair. The effect of doxycycline treatment on MMP and cysteine proteases, and their respective inhibitors, was evaluated by quantitative polymerase chain reaction, Western blot analysis, immunocapture protease activity assays, and immunohistochemistry. Results: Doxycycline was well tolerated and no participants dropped out. Doxycycline treatment reduced aortic wall MMP-3 and MMP-25 messenger RNA expression (P < .045 and P < .014, respectively), selectively suppressed neutrophil collagenase and gelatinase (MMP-8 and MMP-9) protein levels (P < .013 and <.004, respectively), and increased protein levels of the protease inhibitors tissue inhibitor of metalloproteinase 1 and cystatin C (P < .029). As for the apparent selective effect on neutrophil-associated proteases, we sought for a reducing effect on aortic wall neutrophil content that was indeed confirmed by immunohistochemical analysis that revealed a 75% reduction in aneurysm wall neutrophil content (P < .001). Conclusions: Independent of its dose, short-term preoperative doxycycline therapy improves the proteolytic balance in AAA, presumably through an effect on aortic wall neutrophil content. This study provides a rationale for doxycycline treatment in patients with an AAA as well as in other (vascular) conditions involving neutrophil influx such as Kawasaki disease and Behçet disease. [Copyright &y& Elsevier]
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- 2009
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18. Renal Ischemia-Reperfusion Induces Release of Angiopoietin-2 From Human Grafts of Living and Deceased Donors
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Vries, Dorottya K. de, Khairoun, Meriem, Lindeman, Jan H.N., Bajema, Ingeborg M., de Heer, Emile, Roest, Mark, Zonneveld, Anton J. van, van Kooten, Cees, Rabelink, Ton J., Schaapherder, Alexander F., and Reinders, Marlies E.J.
- Abstract
Recent insights suggest that endothelial cell (EC) activation plays a major role in renal ischemia-reperfusion (IR) injury. Interactions between ECs and pericytes via signaling molecules, including angiopoietins, are involved in maintenance of the vascular integrity. Experimental data have shown that enhancement of Angiopoietin (Ang)-1 signaling might be beneficial in renal IR injury. However, little is known about the role of angiopoietins in human renal IR injury.
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- 2013
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19. Mechanical Properties of the Extracellular Matrix of the Aorta Studied by Enzymatic Treatments
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Beenakker, Jan-Willem M., Ashcroft, Brian A., Lindeman, Jan H.N., and Oosterkamp, Tjerk H.
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The microarchitecture of different components of the extracellular matrix (ECM) is crucial to our understanding of the properties of a tissue. In the study presented here, we used a top-down approach to understand how the interplay among different fibers determines the mechanical properties of real tissues. By selectively removing different elements of the arterial wall, we were able to measure the contribution of the different constituents of the ECM to the mechanical properties of the whole tissue. Changes in the network structure were imaged with the use of two-photon microscopy. We used an atomic force microscope to measure changes in the mechanical properties by performing nanoindentation experiments. We show that although the removal of a key element of the ECM reduced the local stiffness by up to 50 times, the remaining tissue still formed a coherent network. We also show how this method can be extended to study the effects of cells on real tissues. This new (to our knowledge) way of studying the ECM will not only help physicists gain a better understanding of biopolymers, it will be a valuable tool for biomedical researchers studying processes such as wound healing and cervix ripening.
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- 2012
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20. Collagen Degradation in the Abdominal Aneurysm
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Abdul-Hussien, Hazem, Soekhoe, Ratna G.V., Weber, Ekkehard, von der Thüsen, Jan H., Kleemann, Robert, Mulder, Adri, van Bockel, J. Hajo, Hanemaaijer, Roeland, and Lindeman, Jan H.N.
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Growth and rupture of abdominal aortic aneurysms (AAAs) result from increased collagen turnover. Collagen turnover critically depends on specific collagenases that cleave the triple helical region of fibrillar collagen. As yet, the collagenases responsible for collagen degradation in AAAs have not been identified. Increased type I collagen degradation products confirmed collagen turnover in AAAs (median values: <1, 43, and 108 ng/mg protein in control, growing, and ruptured AAAs, respectively). mRNA and protein analysis identified neutrophil collagenase [matrix metalloproteinase (MMP)-8] and cysteine collagenases cathepsin K, L, and S as the principle collagenases in growing and ruptured AAAs. Except for modestly increased MMP-14 mRNA levels, collagenase expression was similar in growing and ruptured AAAs (anterior-lateral wall). Evaluation of posttranslational regulation of protease activity showed a threefold increase in MMP-8, a fivefold increase in cathepsins K and L, and a 30-fold increase in cathepsin S activation in growing and ruptured AAAs. The presence of the osteoclastic proton pump indicated optimal conditions for extracellular cysteine protease activity. Protease inhibitor mRNA expression was similar in AAAs and controls, but AAA protein levels of cystatin C, the principle cysteine protease inhibitor, were profoundly reduced (80%). We found indications that this secondary deficiency relates to cystatin C degradation by (neutrophil-derived) proteases.
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- 2007
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21. Up-Regulation and Coexpression of MIF and Matrix Metalloproteinases in Human Abdominal Aortic Aneurysms
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Verschuren, Lars, Lindeman, Jan H.N., Bockel, J. Hajo Van, Abdul-Hussien, Hazem, Kooistra, Teake, and Kleemann, Robert
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Abdominal aortic aneurysm (AAA) is a localized dilatation of the arterial wall as a result of extensive breakdown of its structural proteins by matrix metalloproteinases (MMPs). AAA continuously expand and may eventually rupture, causing high mortality rates. The molecular processes underlying expansion and rupture of AAAare only poorly understood. In this study, evidence was sought for a direct involvement of macrophage migration inhibitory factor (MIF) in the pathogenesis of AAA through up-regulating MMPs, with particular reference to macrophages. To this end, expression and cellular localization of MIF were analyzed in human aortic wall samples of stable AAA and ruptured AAA, and compared with control aorta and atherosclerotic aorta (AS). MIF expression was up-regulated in stable AAA and further intensified in ruptured AAA. The increased aneurysmal MIF expression was paralleled by an enhanced expression of specific MMPs, viz. MMP-1, MMP-9, and MMP-12, and by a decrease of their inhibitors. Immunohistochemical analysis of AAA and AS showed MIF protein in endothelial cells, smooth muscle cells (SMCs), macrophages, and T cells. MMP-1 (in SMCs and macrophages) and MMP-9 (in macrophages) were colocalized with MIF at the cellular level in ruptured AAA. The up-regulation of aneurysmal MIF/MMP expression was associated with an increased content of cytotoxic T cells.Antioxid. Redox Signal. 7, 1195–1202.
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- 2005
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22. Cathepsin K Is the Principal Protease in Giant Cell Tumor of Bone
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Lindeman, Jan H.N., Hanemaaijer, Roeland, Mulder, Adri, Dijkstra, P.D. Sander, Szuhai, Károly, Bromme, Dieter, Verheijen, Jan H., and Hogendoorn, Pancras C.W.
- Abstract
Giant cell tumor (GCT) of bone is a neoplasm of bone characterized by a localized osteolytic lesion. The nature of GCT is an enigma and the cell type(s) and protease(s) responsible for the extensive localized clinicoradiological osteolysis remain unresolved. We evaluated protease expression and cellular distribution of the proteolytic machinery responsible for the osteolysis. mRNA profiles showed that cathepsin K, cathepsin L, and matrix metalloproteinase (MMP)-9 were the preferentially expressed collagenases. Moderate expression was found for MMP-13, MMP-14, and cathepsin S. Specific protease activity assays revealed high cathepsin K activity but showed that MMP-9 was primarily present (98%) as inactive proenzyme. Activities of MMP-13 and MMP-14 were low. Immunohistochemistry revealed a clear spatial distribution: cathepsin K, its associated proton pump V-H+-ATPase, and MMP-9 were exclusively expressed in osteoclast-like giant cells, whereas cathepsin L expression was confined to mononuclear cells. To explore a possible role of cathepsin L in osteolysis, GCT-derived, cathepsin L-expressing, mononuclear cells were cultured on dentine disks. No evidence of osteolysis by these cells was found. These results implicate cathepsin K as the principal protease in GCT and suggest that osteoclast-like giant cells are responsible for the osteolysis. Inhibition of cathepsin K or its associated proton-pump may provide new therapeutic opportunities for GCT.
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- 2004
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23. Ghrelin and the Hyposomatotropism of Obesity
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Lindeman, Jan H.N., Pijl, Hanno, Dielen, François M.H., Lentjes, Eef G.W.M., Leuven, Cees, and Kooistra, Teake
- Abstract
Objective:Human obesity is characterized by growth hormone (GH) deficiency, which appears primarily related to a central pattern of obesity and is reverted on weight loss. As yet, the metabolic basis of the GH deficiency remains to be elucidated. The recently discovered endogenous ligand for the GH secretagogue receptor, ghrelin, stimulates GH secretion when administered to rodents or healthy humans. It may thus be hypothesized that low ghrelin levels underlie the hyposomatropism in obesity. Research Methods and Procedures:We have tested this hypothesis in individuals with widely varying body mass and fat distribution and evaluated whether the improved GH concentrations on weight loss are associated with enhanced ghrelin levels. Results:Both plasma GH and ghrelin levels were reciprocally related with body mass index (r= −0.67, p< 0.001). However, whereas 24‐hour GH secretion was negatively related to the visceral fat area (r= −0.72, p< 0.01), ghrelin levels showed a positive relationship with the visceral fat area (r= 0.49, p< 0.02). Weight loss resulted in increased GH secretion (median 24‐hour GH area under the curve: 1983 vs. 4024 mU/day before and after weight loss, respectively; p< 0.01) but did not affect ghrelin levels. No relationship could be found between GH and ghrelin plasma levels in obese subjects when comparing diurnal concentration profiles. Discussion:We showed that plasma ghrelin and GH levels are both reciprocally related with body mass index, but no causative relationship could be demonstrated between low ghrelin levels and the hyposomatropism in human obesity.
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- 2002
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24. Metabolic needs of the kidney graft undergoing normothermic machine perfusion
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Arykbaeva, Asel S., de Vries, Dorottya K., Doppenberg, Jason B., Engelse, Marten A., Hankemeier, Thomas, Harms, Amy C., Wijermars, Leonie G., Schaapherder, Alexander F., Bakker, Jaap A., Ploeg, Rutger J., Alwayn, Ian P.J., and Lindeman, Jan H.N.
- Abstract
Normothermic machine perfusion (NMP) is emerging as a novel preservation strategy. During NMP, the organ is maintained in a metabolically active state that may not only provide superior organ preservation, but that also facilitates viability testing before transplantation, and ex situresuscitation of marginal kidney grafts. Although the prevailing perfusion protocols for renal NMP are refined from initial pioneering studies concerning short periods of NMP, it could be argued that these protocols are not optimally tailored to address the putatively compromised metabolic plasticity of marginal donor grafts (i.e., in the context of viability testing and/or preservation), or to meet the metabolic prerequisites associated with prolonged perfusions and the required anabolic state in the context of organ regeneration. Herein, we provide a theoretical framework for the metabolic requirements for renal NMP. Aspects are discussed along the lines of carbohydrates, fatty acids, amino acids, and micronutrients required for optimal NMP of an isolated kidney. In addition, considerations for monitoring aspects of metabolic status during NMP are discussed.
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- 2021
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25. Adventitial adipogenic degeneration is an unidentified contributor to aortic wall weakening in the abdominal aortic aneurysm.
- Author
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Doderer, Stefan A., Gäbel, Gabor, Kokje, Vivianne B.C., Northoff, Bernd H., Holdt, Lesca M., Hamming, Jaap F., and Lindeman, Jan H.N.
- Abstract
Objective The processes driving human abdominal aortic aneurysm (AAA) progression are not fully understood. Although antiinflammatory and proteolytic strategies effectively quench aneurysm progression in preclinical models, so far all clinical interventions failed. These observations hint at an incomplete understanding of the processes involved in AAA progression and rupture. Interestingly, strong clinical and molecular associations exist between popliteal artery aneurysms (PAAs) and AAAs; however, PAAs have an extremely low propensity to rupture. We thus reasoned that differences between these aneurysms may provide clues toward (auxiliary) processes involved in AAA-related wall debilitation. A better understanding of the pathophysiologic processes driving AAA growth can contribute to pharmaceutical treatments in the future. Methods Aneurysmal wall samples were collected during open elective and emergency repair. Control perirenal aorta was obtained during kidney transplantation, and reference popliteal tissue obtained from the anatomy department. This study incorporates various techniques including (immuno)histochemistry, Western Blot, quantitative polymerase chain reaction, microarray, and cell culture. Results Histologic evaluation of AAAs, PAAs, and control aorta shows extensive medial (PAA) and transmural fibrosis (AAA), and reveals abundant adventitial adipocytes aggregates as an exclusive phenomenon of AAAs ( P < .001). Quantitative polymerase chain reaction, immunohistochemistry, Western blotting, and microarray analysis showed enrichment of adipogenic mediators (C/EBP family P = .027; KLF5 P < .000; and peroxisome proliferator activated receptor-γ, P = .032) in AAA tissue. In vitro differentiation tests indicated a sharply increased adipogenic potential of AAA adventitial mesenchymal cells ( P < .0001). Observed enrichment of adipocyte-related genes and pathways in ruptured AAA ( P < .0003) supports an association between the extent of fatty degeneration and rupture. Conclusions This translational study identifies extensive adventitial fatty degeneration as an ignored and distinctive feature of AAA disease. Enrichment of adipocyte genesis and adipocyte-related genes in ruptured AAA point to an association between the extent of fatty degeneration and rupture. This observation may (partly) explain the failure of medical therapy and could provide a lead for pharmaceutical alleviation of AAA progression. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
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