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Wahlberg, Eric
Publications (10 of 21) Show all publications
Sigvant, B., Lundin, F. & Wahlberg, E. (2016). The Risk of Disease Progression in Peripheral Arterial Disease is Higher than Expected: A Meta-Analysis of Mortality and Disease Progression in Peripheral Arterial Disease. European Journal of Vascular and Endovascular Surgery, 51(3), 395-403
Open this publication in new window or tab >>The Risk of Disease Progression in Peripheral Arterial Disease is Higher than Expected: A Meta-Analysis of Mortality and Disease Progression in Peripheral Arterial Disease
2016 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 51, no 3, p. 395-403Article, review/survey (Refereed) Published
Abstract [en]

Objective: Peripheral arterial, disease (PAD) afflicts up to 20% of older people and is associated with a high risk of cardiovascular (CV) morbidity, but a rather low risk of progression of leg symptoms. These risk estimations are largely taken from cohort studies performed 20 years ago. To test the validity of this, available data were systematically reviewed and attempts were made to perform meta-analyses of CV risk and disease progression. Methods: A database literature search was conducted of the period 1990-2015 using related subject headings. Inclusion criteria were cohort studies for PAD, sample size >100 subjects, follow up time >= 1 year, and studies presenting endpoints covering mortality and/or CV events. Analyses were performed for a reference population, as well as groups with asymptomatic PAD (APAD), symptomatic PAD, and subjects with ankle brachial index <0.9. Results: Of 354 identified articles, 35 were eligible for systematic review. Sample size varied between 109 and 16,440 subjects. Mean age in the cohorts ranged from 56 to 81 years (SD 10.8) and mean follow up was 6.3 years (range 1-13). Most included patients with symptomatic PAD had IC (91%). Symptomatic PAD subjects had higher 5 year cumulative CV mortality than the reference population, 13% versus 5%. During follow up, approximately 7% of APAD patients progressed to IC, and 21% of IC patients were diagnosed as having critical limb ischemia, with 4-27% undergoing amputations. Conclusion: The risk to the limb is underestimated in PAD patients, whereas the CV related morbidity is more moderate than stated in the guidelines. The latter observation is especially valid for IC patients. These findings should be considered when evaluating patients for treatment. (C) 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
W B SAUNDERS CO LTD, 2016
Keywords
Amputation; Mortality; Natural history; Peripheral arterial disease
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-127280 (URN)10.1016/j.ejvs.2015.10.022 (DOI)000372689800015 ()26777541 (PubMedID)
Available from: 2016-04-20 Created: 2016-04-19 Last updated: 2017-04-24
Yang, Y., Zhang, Y., Cao, Z., Ji, H., Yang, X., Iwamoto, H., . . . Cao, Y. (2013). Anti-VEGF- and anti-VEGF receptor-induced vascular alteration in mouse healthy tissues. Proceedings of the National Academy of Sciences of the United States of America, 110(29), 12018-12023
Open this publication in new window or tab >>Anti-VEGF- and anti-VEGF receptor-induced vascular alteration in mouse healthy tissues
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2013 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, no 29, p. 12018-12023Article in journal (Refereed) Published
Abstract [en]

Systemic therapy with anti-VEGF drugs such as bevacizumab is widely used for treatment of human patients with various solid tumors. However, systemic impacts of such drugs in host healthy vasculatures remain poorly understood. Here, we show that, in mice, systemic delivery of an anti-VEGF or an anti-VEGF receptor (VEGFR)-2 neutralizing antibody caused global vascular regression. Among all examined tissues, vasculatures in endocrine glands, intestinal villi, and uterus are the most affected in response to VEGF or VEGFR-2 blockades. Thyroid vascular fenestrations were virtually completely blocked by VEGF blockade, leading to marked accumulation of intraendothelial caveolae vesicles. VEGF blockade markedly increased thyroid endothelial cell apoptosis, and withdrawal of anti-VEGF resulted in full recovery of vascular density and architecture after 14 d. Prolonged anti-VEGF treatment resulted in a significant decrease of the circulating level of the predominant thyroid hormone free thyroxine, but not the minimal isoform of triiodothyronine, suggesting that chronic anti-VEGF treatment impairs thyroid functions. Conversely, VEGFR-1-specific blockade produced virtually no obvious phenotypes. These findings provide structural and functional bases of anti-VEGF-specific drug-induced side effects in relation to vascular changes in healthy tissues. Understanding anti-VEGF drug-induced vascular alterations in healthy tissues is crucial to minimize and even to avoid adverse effects produced by currently used anti-VEGF-specific drugs.

Place, publisher, year, edition, pages
National Academy of Sciences, 2013
Keywords
angiogenesis, antiangiogenic therapy, off-tumor targets, vascular homeostasis, vessel regression
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-102114 (URN)10.1073/pnas.1301331110 (DOI)000322086100078 ()23818623 (PubMedID)
Available from: 2013-12-01 Created: 2013-12-01 Last updated: 2017-12-06Bibliographically approved
Dong, M., Yang, X., Lim, S., Cao, Z., Honek, J., Lu, H., . . . Cao, Y. (2013). Cold Exposure Promotes Atherosclerotic Plaque Growth and Instability via UCP1-Dependent Lipolysis. Cell Metabolism, 18(1), 118-129
Open this publication in new window or tab >>Cold Exposure Promotes Atherosclerotic Plaque Growth and Instability via UCP1-Dependent Lipolysis
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2013 (English)In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 18, no 1, p. 118-129Article in journal (Refereed) Published
Abstract [en]

Molecular mechanisms underlying the cold-associated high cardiovascular risk remain unknown. Here, we show that the cold-triggered food-intake-independent lipolysis significantly increased plasma levels of small low-density lipoprotein (LDL) remnants, leading to accelerated development of atherosclerotic lesions in mice. In two genetic mouse knockout models (apolipoprotein E-/- [ApoE(-/-)] and LDL receptor(-/-) [Ldlr(-/-)] mice), persistent cold exposure stimulated atherosclerotic plaque growth by increasing lipid deposition. Furthermore, marked increase of inflammatory cells and plaque-associated microvessels were detected in the cold-acclimated ApoE(-/-) and Ldlr(-/-) mice, leading to plaque instability. Deletion of uncoupling protein 1 (UCP1), a key mitochondrial protein involved in thermogenesis in brown adipose tissue (BAT), in the ApoE(-/-) strain completely protected mice from the cold-induced atherosclerotic lesions. Cold acclimation markedly reduced plasma levels of adiponectin, and systemic delivery of adiponectin protected ApoE(-/-) mice from plaque development. These findings provide mechanistic insights on low-temperature-associated cardiovascular risks.

Place, publisher, year, edition, pages
Elsevier (Cell Press), 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-101394 (URN)10.1016/j.cmet.2013.06.003 (DOI)000326267100015 ()
Note

Funding Agencies|Swedish Research Council||Swedish Cancer Foundation||Karolinska Institute Foundation||Karolinska Institute Distinguished Professor Award||Torsten Soderbergs Foundation||Tianjin Natural Science Foundation (CMM-Tianjin)|09ZCZDSF04400|ImClone Systems of Eli Lilly||European Union Integrated Project of Metoxia|222741|European Research Council (ERC) advanced grant ANGIOFAT|250021|National 973 Basic Research Program of China|2011CB5039062012CB518603|National High-Tech Research and Development Program of China|2012AA02A510|Program of Introducing Talents of Discipline to Universities|B07035|State Program of National Natural Science Foundation of China for Innovative Research Group|81021001|National Natural Science Foundation of China|811002078117325181100102812703508100012681000127|

Available from: 2013-11-22 Created: 2013-11-21 Last updated: 2017-12-06
Dahl Jensen, L., Cao, Z., Nakamura, M., Yang, Y., Brautigam, L., Andersson, P., . . . Cao, Y. (2012). Opposing Effects of Circadian Clock Genes Bmal1 and Period2 in Regulation of VEGF-Dependent Angiogenesis in Developing Zebrafish. Cell Reports, 2(2), 231-241
Open this publication in new window or tab >>Opposing Effects of Circadian Clock Genes Bmal1 and Period2 in Regulation of VEGF-Dependent Angiogenesis in Developing Zebrafish
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2012 (English)In: Cell Reports, ISSN 2211-1247, Vol. 2, no 2, p. 231-241Article in journal (Refereed) Published
Abstract [en]

Molecular mechanisms underlying circadian-regulated physiological processes remain largely unknown. Here, we show that disruption of the circadian clock by both constant exposure to light and genetic manipulation of key genes in zebrafish led to impaired developmental angiogenesis. A bmal1-specific morpholino inhibited developmental angiogenesis in zebrafish embryos without causing obvious nonvascular phenotypes. Conversely, a period2 morpholino accelerated angiogenic vessel growth, suggesting that Bmal1 and Period2 display opposing angiogenic effects. Using a promoter-reporter system consisting of various deleted vegf-promoter mutants, we show that Bmal1 directly binds to and activates the vegf promoter via E-boxes. Additionally, we provide evidence that knockdown of Bmal1 leads to impaired Notch-inhibition-induced vascular sprouting. These results shed mechanistic insight on the role of the circadian clock in regulation of developmental angiogenesis, and our findings may be reasonably extended to other types of physiological or pathological angiogenesis.

Place, publisher, year, edition, pages
Elsevier (Cell Press), 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85304 (URN)10.1016/j.celrep.2012.07.005 (DOI)000309715100004 ()
Note

Funding Agencies|Swedish Research Council||Swedish Cancer Foundation||Karolinska Institute Foundation||Karolinska Institute||Tianjin Natural Science Foundation (CMM-Tianjin)|09ZCZDSF04400|Torsten Soderbergs Foundation||European Union|222741|European Research Council (ERC)|250021|

Available from: 2012-11-16 Created: 2012-11-15 Last updated: 2017-03-27Bibliographically approved
Sigvant, B., Henriksson, M., Lundin, F. & Wahlberg, E. (2011). Asymptomatic peripheral arterial disease: is pharmacological prevention of cardiovascular risk cost-effective?. EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION and REHABILITATION, 18(2), 254-261
Open this publication in new window or tab >>Asymptomatic peripheral arterial disease: is pharmacological prevention of cardiovascular risk cost-effective?
2011 (English)In: EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION and REHABILITATION, ISSN 1741-8267, Vol. 18, no 2, p. 254-261Article in journal (Refereed) Published
Abstract [en]

Peripheral arterial disease (PAD) is associated with an increased risk of early death in cardiovascular (CV) disease. The majority of PAD subjects are asymptomatic with a prevalence of 11 per cent among the elderly. Long-term drug prevention aiming to minimize disease progression and CV events in these subjects is probably beneficial, but expensive. The purpose of this analysis was to evaluate the cost-effectiveness of pharmacological risk reduction in subclinical PAD. Long-term costs and quality-adjusted life years (QALYs) were estimated by employing a decision-analytic model for ACE-inhibitor, statin, aspirin and non-aspirin anti-platelet therapy. Rates of CV events without treatment were derived from epidemiological studies and event rate reduction were retrieved from clinical trials. Costs and health-related quality of life estimates were obtained from published sources. All four drugs reduced CV events. Using ACE-inhibition resulted in a heart rate (HR) of 0.67 (95% CI: 0.55-0.79), statins 0.74 (0.70-0.79), and clopidogrel 0.72 (0.43-1.00). Aspirin had a HR of 0.87 and the 95% CI passed included one (0.72-1.03). ACE-inhibition was associated with the largest reduction in events leading to the highest gain in QALYs (7.95). Furthermore, ACE-inhibitors were associated with the lowest mean cost (sic)40.556. In conclusion, while all drugs reduced CV events, ACE-inhibition was the most cost-effective. These results suggest that we should consider efforts to identify patients with asymptomatic PAD and, when identified, offer ACE-inhibition.

Place, publisher, year, edition, pages
Lippincott Williams and Wilkins, 2011
Keywords
Cost-benefit analysis, peripheral vascular disease, pharmacological prevention
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-68224 (URN)10.1177/1741826710389368 (DOI)000289895800016 ()
Available from: 2011-05-13 Created: 2011-05-13 Last updated: 2012-03-15
Bergqvist, D., Säwe, J. & Wahlberg, E. (2011). Benartärsjukdom – inget nytt sedan SBU-rapporten. Läkartidningen, 108(8), 403-405
Open this publication in new window or tab >>Benartärsjukdom – inget nytt sedan SBU-rapporten
2011 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 8, p. 403-405Article in journal (Other academic) Published
Abstract [sv]

Huvudresultaten i SBU:s ben­ischemirapport sammanfattas.

Inga nya studier av öppna eller endovaskulära behandlingsmetoder har nämnvärt förändrat behandlingsstragegin vid benartärsjukdom.

Ett läkemedel – cilostazol – har godkänts för symtomatisk behandling vid claudicatio intermittens.

Kontrollerade studier pågår för att lokalt stimulera kärlnybildning i ischemisk muskulatur.

Abstract [en]

In 2007 a report on leg ischemia was published by SBU (Board of Health Technology Assessment in Sweden). This paper summarizes the results of this report and analyzes further investigations of interest. No new open surgical or endovascular methods have been reported. Cilostazol has been approved to increase the walking distance in claudicants. Ongoing trials are evaluating the effect of stem cells and angiogenic factors to treat critical limb ischaemia.

Place, publisher, year, edition, pages
Läkartidningen Förlag, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-76052 (URN)
Available from: 2012-03-24 Created: 2012-03-24 Last updated: 2017-12-07
Sigvant, B., Lundin, F., Nilsson, B., Bergqvist, D. & Wahlberg, E. (2011). Differences in presentation of symptoms between women and men with intermittent claudication. BMC Cardiovascular Disorders, 11(39)
Open this publication in new window or tab >>Differences in presentation of symptoms between women and men with intermittent claudication
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2011 (English)In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 11, no 39Article in journal (Refereed) Published
Abstract [en]

Background: More women than men have PAD with exception for the stage intermittent claudication (IC). The purpose of this study was to evaluate differences in disease characteristics between men and women when using current diagnostic criteria for making the diagnosis IC, defined as ABI less than 0.9 and walking problems. Study Design: Cohort study Methods: 5040 elderly (median age 71) subjects participated in a point-prevalence study 2004. They had their ABI measured and filled out questionnaires covering medical history, current medication, PAD symptoms and walking ability. The prevalence of IC was 6.5% for women and 7.2% for men (P = 0.09). A subset of subjects with IC (N = 56) was followed up four years later with the same procedures. They also performed additional tests aiming to determine all factors influencing walking ability. Results: Men with IC had more concomitant cardiovascular disease and a more profound smoking history than women. Women, on the other hand, reported a lower walking speed (P less than 0.01) and more joint problems (P = 0.018). In the follow up cohort ABI, walking ability and amount of atherosclerosis were similar among the sexes, but women more often reported atypical IC symptoms. Conclusion: Sex differences in the description of IC symptoms may influence diagnosis even if objective features of PAD are similar. This may influence accuracy of prevalence estimates and selection to treatment.

Place, publisher, year, edition, pages
BioMed Central, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69845 (URN)10.1186/1471-2261-11-39 (DOI)000292822300001 ()
Note
Original Publication: Birgitta Sigvant, Fredrik Lundin, Bo Nilsson, David Bergqvist and Eric Wahlberg, Differences in presentation of symptoms between women and men with intermittent claudication, 2011, BMC Cardiovascular Disorders, (11), 39. http://dx.doi.org/10.1186/1471-2261-11-39 Licensee: BioMed Central http://www.biomedcentral.com/ Available from: 2011-08-10 Created: 2011-08-08 Last updated: 2017-12-08
Dahl Jensen, L., Rouhi, P., Cao, Z., Länne, T., Wahlberg, E. & Cao, Y. (2011). Zebrafish Models to Study Hypoxia-Induced Pathological Angiogenesis in Malignant and Nonmalignant Diseases. Birth Defects Research. Part C: Embryo Today Reviews, 93(2), 182-193
Open this publication in new window or tab >>Zebrafish Models to Study Hypoxia-Induced Pathological Angiogenesis in Malignant and Nonmalignant Diseases
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2011 (English)In: Birth Defects Research. Part C: Embryo Today Reviews, ISSN 1542-975X, Vol. 93, no 2, p. 182-193Article, review/survey (Refereed) Published
Abstract [en]

Most in vivo preclinical disease models are based on mouse and other mammalian systems. However, these rodent-based model systems have considerable limitations to recapitulate clinical situations in human patients. Zebrafish have been widely used to study embryonic development, behavior, tissue regeneration, and genetic defects. Additionally, zebrafish also provides an opportunity to screen chemical compounds that target a specific cell population for drug development. Owing to the availability of various genetically manipulated strains of zebrafish, immune privilege during early embryonic development, transparency of the embryos, and easy and precise setup of hypoxia equipment, we have developed several disease models in both embryonic and adult zebrafish, focusing on studying the role of angiogenesis in pathological settings. These zebrafish disease models are complementary to the existing mouse models, allowing us to study clinically relevant processes in cancer and nonmalignant diseases, which otherwise would be difficult to study in mice. For example, dissemination and invasion of single human or mouse tumor cells from the primary site in association with tumor angiogenesis can be studied under normoxia or hypoxia in zebrafish embryos. Hypoxia-induced retinopathy in the adult zebrafish recapitulates the clinical situation of retinopathy development in diabetic patients or age-related macular degeneration. These zebrafish disease models offer exciting opportunities to understand the mechanisms of disease development, progression, and development of more effective drugs for therapeutic intervention.

Place, publisher, year, edition, pages
John Wiley and Sons.Ltd, 2011
Keywords
zebrafish; angiogenesis; cancer; metastasis; retinopathy; hypoxia
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69886 (URN)10.1002/bdrc.20203 (DOI)000291545600007 ()
Available from: 2011-08-09 Created: 2011-08-08 Last updated: 2017-03-27
Koraen, L. & Wahlberg, E. (2010). Claudicatio intermittens. Läkartidningen, 107(29-31), 1774-1779
Open this publication in new window or tab >>Claudicatio intermittens
2010 (English)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 29-31, p. 1774-1779Article in journal (Refereed) Published
Abstract [en]

[No abstract available]

Place, publisher, year, edition, pages
Lakartidningen, 2010
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-59081 (URN)
Available from: 2010-09-21 Created: 2010-09-09 Last updated: 2017-12-12
Wahlgren, C.-M., Wahlberg, E. & Olofsson, P. (2010). Endovascular Treatment in Postthrombotic Syndrome. Vascular and Endovascular Surgery, 44(5), 356-360
Open this publication in new window or tab >>Endovascular Treatment in Postthrombotic Syndrome
2010 (English)In: Vascular and Endovascular Surgery, ISSN 1538-5744, Vol. 44, no 5, p. 356-360Article in journal (Refereed) Published
Abstract [en]

Background: The postthrombotic syndrome is a chronic complication of deep venous thrombosis that leads to considerable pain and suffering to patients. We evaluated our experience of endovascular treatment for patients with chronic postthrombotic femoroiliocaval venous disease.

Materials and Methods: From January 2003 through December 2007, 50 patients (51 limbs; 60% women; mean age 45 years; range: 24-74 years) with chronic postthrombotic venous disease were referred to our institution for interventional assessment. All patients underwent duplex ultrasonography as well as ascending and descending venography. The CEAP (clinical, etiologic, anatomic, and pathophysiologic classification) clinical scores were class 0 (no signs) in 2% of limbs, class 3 (edema) in 63%, class 4a (pigmentation or eczema) in 18%, class 5 (healed venous ulcer) in 14%, and class 6 (active venous ulcer) in 4%. The etiology was secondary (postthrombotic) in all patients. The anatomical distribution of reflux and obstruction were deep veins in 63% and a combination of deep and superficial veins in 37%. The underlying pathophysiology due to obstruction of the deep venous outflow with no reflux was found in 25% of limbs, only reflux was found in 14%, and a combination of obstruction and reflux was found in 61%.

Results: There were 21 limbs in 20 (38%) patients that underwent endovascular and/or surgical treatment. One limb underwent femoral endovenectomy and 1 limb superficial femoral vein to deep femoral vein transposition. In all, 19 limbs were scheduled for endovascular treatment. The technical success rate was 84%, 3 limbs with iliac vein occlusions could not be recanalized. A total of 11 patients (11 limbs) underwent solely endovascular intervention and 4 patients (5 limbs) underwent endovascular intervention combined with femoral endovenectomy. The endovascular and surgical procedures were performed with no perioperative or postoperative mortality as well as no major bleeding or cardiac, pulmonary, or renal 30-day complications. Early thrombosis (<30 days) of the stented iliac veins occurred in 3 limbs which were lysed and restented successfully. The mean follow-up time was 23 months (range: 1-69 months). Primary and assisted-primary/secondary patency rates at 12 months were 61% and 81%, respectively. The Venous Clinical Severity score was 9.1 (range: 5-15) before endovascular treatment and 6.0 (range: 3-13) after the treatment (P < .0001). There were 30 patients (62%) with symptoms attributable to venous dysfunction or with deep venous pathology that did not undergo interventional treatment after workup. These patients continued with appropriate thromboprophylaxis and elastic compression stockings.

Conclusion: Endovascular treatment of chronic postthrombotic femoroiliocaval venous disease is a safe technique that can be performed with acceptable patency rates in this challenging patient population.

Place, publisher, year, edition, pages
Sage Publications, 2010
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-67142 (URN)10.1177/1538574410369710 (DOI)000279225700006 ()20484062 (PubMedID)
Available from: 2011-03-31 Created: 2011-03-31 Last updated: 2014-09-24Bibliographically approved
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