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Papers by Lysette Broekhuizen

Research paper thumbnail of Cardiac magnetic resonance in advanced heart failure

Echocardiography, Jun 1, 2024

Research paper thumbnail of Serial Screening in a Young Athletic Male Carrier of Phospholamban R14 Deletion

Journal of cardiovascular magnetic resonance, 2024

Research paper thumbnail of Non-Invasive Assessment of Multivalvular Heart Disease: A Comprehensive Review

Reviews in Cardiovascular Medicine, Jan 15, 2024

Research paper thumbnail of Screening for coronary artery disease using primary evaluation with coronary CTA in aviation medicine (SUSPECT): study design

International Journal of Clinical Trials

Background: Sudden in-flight incapacitation of aircrew may cause an airplane crash. Important cau... more Background: Sudden in-flight incapacitation of aircrew may cause an airplane crash. Important causes are major adverse cardiac events, such as myocardial infarction and sudden cardiac arrest. Aircrew of the Royal Netherlands Air Force (RNLAF) are required to undergo periodic cardiac screening, including bicycle exercise-testing. Unfortunately, this modality lacks diagnostic accuracy for relevant coronary artery disease (CAD) in low-risk populations similar to military aircrew. Cardiac CT, however, comprising Coronary Artery Calcium score (CACS) and coronary CT angiography (CCTA), is able to adequately detect (subclinical) CAD with high negative predictive values in low-risk populations and may provide opportunity for early interventions. Methods: This was a prospective, single-center, cohort study of 250 military aircrew. Asymptomatic aircrew ≥40 years are asked to undergo a voluntary cardiac CT following routine aeromedical examination. Prevalence and severity of CAD will be descri...

Research paper thumbnail of Reduction of monocyte chemoattractant protein 1 and macrophage migration inhibitory factor by a polyphenol-rich extract in subjects with clustered cardiometabolic risk factors

British Journal of Nutrition, Jun 28, 2011

Research paper thumbnail of The association between the gene encoding 5-lipoxygenase activating protein and abdominal aortic aneurysms

Atherosclerosis, Feb 1, 2012

Research paper thumbnail of Left Atrio-ventricular Coupling Index as a Predictor of Diastolic Dysfunction in Patients After Myocardial Infarction

Journal of cardiovascular magnetic resonance, 2024

Research paper thumbnail of Effects of SUlodexide on damaged endothelial Glycocalyx in pAtients with diabetes Mellitus type two: Reversing damage

http://isrctn.org/>, 2012

Research paper thumbnail of The association between the 5-LipOxygenase pathway and abdominal aortic aneurysms

http://isrctn.org/>, 2012

Research paper thumbnail of The Role of Non-Invasive Multimodality Imaging in Chronic Coronary Syndrome: Anatomical and Functional Pathways

Diagnostics

Coronary artery disease (CAD) is one of the major causes of mortality and morbidity worldwide, wi... more Coronary artery disease (CAD) is one of the major causes of mortality and morbidity worldwide, with a high socioeconomic impact. Currently, various guidelines and recommendations have been published about chronic coronary syndromes (CCS). According to the recent European Society of Cardiology guidelines on chronic coronary syndrome, a multimodal imaging approach is strongly recommended in the evaluation of patients with suspected CAD. Today, in the current practice, non-invasive imaging methods can assess coronary anatomy through coronary computed tomography angiography (CCTA) and/or inducible myocardial ischemia through functional stress testing (stress echocardiography, cardiac magnetic resonance imaging, single photon emission computed tomography—SPECT, or positron emission tomography—PET). However, recent trials (ISCHEMIA and REVIVED) have cast doubt on the previous conception of the management of patients with CCS, and nowadays it is essential to understand the limitations and ...

Research paper thumbnail of Atherogenic progression in the innominate- (white bars) and left subclavian (black bars) artery from <i>apoE<sup>−/−</sup></i> mice on a combined Western-type atherogenic diet with inactive- or active hyaluronidase infusion

<p>(A) Distribution and level of advanced plaque areas, given µm<sup>2</sup> ×1... more <p>(A) Distribution and level of advanced plaque areas, given µm<sup>2</sup> ×10.000. Distribution and percentage of (B) collagen or (C) glycosaminoglycan within each plaque area. Distribution of individual macrophage areas within each plaque area (D), given in µm<sup>2</sup>.</p

Research paper thumbnail of Systemic parameters of <i>apoE<sup>−/−</sup></i> mice on NC or HFC for 6- or 10 weeks w/o a final 4 week hyaluronidase infusion

<p>Systemic parameters of <i>apoE<sup>−/−</sup></i> mice on NC or H... more <p>Systemic parameters of <i>apoE<sup>−/−</sup></i> mice on NC or HFC for 6- or 10 weeks w/o a final 4 week hyaluronidase infusion.</p

Research paper thumbnail of Photomicrographs of Sirius red-stained lesions within two major vessels branching from the aortic arch with a difference in onset of atherogenic development

<p>The (A, B, C) innominate- (early start) and (D, E, F) left subclavian artery (later star... more <p>The (A, B, C) innominate- (early start) and (D, E, F) left subclavian artery (later start) from <i>apoE<sup>−/−</sup></i> mice on (A, D) a Western-type atherogenic diet alone, or in combination with (B, E) inactive- or (C, F) active hyaluronidase infusion, (inset F) Higher magnification of Sirius red-stained lesion within the left subclavian artery from <i>apoE<sup>−/−</sup></i> mice on a combined Western-type atherogenic diet and active hyaluronidase infusion. Arrow head indicates absence of long stretches of the intimal layer underneath a plaque. Bar = 0.2 mm, bar inset = 50 µm.</p

Research paper thumbnail of Renal morphology in <i>apoE<sup>−/−</sup></i> mice on HFC for 10 weeks with a final 4 week hyaluronidase infusion

<p>Renal morphology in <i>apoE<sup>−/−</sup></i> mice on HFC for 10... more <p>Renal morphology in <i>apoE<sup>−/−</sup></i> mice on HFC for 10 weeks with a final 4 week hyaluronidase infusion.</p

Research paper thumbnail of Renal morphology of <i>periodic acid Schiff’s</i> stained (PAS) glomeruli of <i>apoE<sup>−/−</sup></i> mice on a combined Western-type atherogenic diet with (A) inactive- or (B)active hyaluronidase infusion

<p>Bar = 50 µm.</p

Research paper thumbnail of Endothelial Surface Layer Degradation by Chronic Hyaluronidase Infusion Induces Proteinuria in Apolipoprotein E-Deficient Mice

PLoS ONE, 2010

Objective: Functional studies show that disruption of endothelial surface layer (ESL) is accompan... more Objective: Functional studies show that disruption of endothelial surface layer (ESL) is accompanied by enhanced sensitivity of the vasculature towards atherogenic stimuli. However, relevance of ESL disruption as causal mechanism for vascular dysfunction remains to be demonstrated. We examined if loss of ESL through enzymatic degradation would affect vascular barrier properties in an atherogenic model. Methods: Eight week old male apolipoprotein E deficient mice on Western-type diet for 10 weeks received continuous active or heat-inactivated hyaluronidase (10 U/hr, i.v.) through an osmotic minipump during 4 weeks. Blood chemistry and anatomic changes in both macrovasculature and kidneys were examined. Results: Infusion with active hyaluronidase resulted in decreased ESL (0.3260.22 mL) and plasma volume (1.0360.18 mL) compared to inactivated hyaluronidase (0.5260.29 mL and 1.2860.08 mL, p,0.05 respectively).Active hyaluronidase increased proteinuria compared to inactive hyaluronidase (0.2760.02 vs. 0.1560.01 mg/mg protein/creatinin, p,0.05) without changes in glomerular morphology or development of tubulo-interstitial inflammation. Atherosclerotic lesions in the aortic branches showed increased matrix production (collagen, 3265 vs. 1863%; glycosaminoglycans, 1165 vs. 0.160.01%, active vs. inactive hyaluronidase, p,0.05). Conclusion: ESL degradation in apoE deficient mice contributes to reduced increased urinary protein excretion without significant changes in renal morphology. Second, the induction of compositional changes in atherogenic plaques by hyaluronidase point towards increased plaque vulnerability. These findings support further efforts to evaluate whether ESL restoration is a valuable target to prevent (micro) vascular disease progression.

Research paper thumbnail of Aortic regurgitation: A multimodality approach

Journal of Clinical Ultrasound

Research paper thumbnail of Sulfated glycosaminoglycans restore glycocalyx barrier properties of cultured endothelial cells in hyperglycemia

The FASEB Journal, 2008

Introduction: Microalbuminuria is a clinical parameter of vascular dysfunction in patients with d... more Introduction: Microalbuminuria is a clinical parameter of vascular dysfunction in patients with diabetes. The endothelial glycocalyx plays a role in regulation of vascular permeability. Therapeutic interventions using a mixture of glycosaminoglycans (GAGs) containing 80% heparin and 20% dermatan sulphate (sulodexide) have been shown to improve vascular barrier function by reducing microalbuminuria. Therefore we hypothesized that exogenous GAGs attenuate hyperglycemia-induced increases in endothelial permeability for albumin by restoring barrier properties of the endothelial glycocalyx. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured on semi-permeable inserts and exposed to normo-(5 mM) or hyperglycemia (25 mM) for 4 days, last 24 h in presence of the GAG mixture. Endothelial permeability was assessed by determining FITC-labeled albumin transfer over the monolayer (3 hours). Additionally, the glycocalyx glucosamine sugar residues on the endothelial cells were visualized with LEA-lectin staining. Results: Albumin permeability of endothelial cells under hyperglycemia was increased to 122 ± 8% (p < 0.01) compared to normoglycemia. Changes in albumin permeability under hyperglycemia normalized to normoglycemic control condition was-4 ± 3% (p < 0.05) in the presence of 0.06μg/mL sulodexide. Additionally, LEA-lectin revealed a 28 ± 1% (p < 0.05) increase in glucosamine staining in hyperglycemic cells in the presence of the GAG mix. Conclusion: GAG supplementation reverses the increased trans-endothelial albumin leakage under hyperglycemic conditions by restoring the barrier properties of the endothelial glycocalyx layer in vitro.

Research paper thumbnail of Renal protein leakage of <i>apoE<sup>−/−</sup></i> mice on normal chow (NC) or on a Western-type atherogenic diet (HFC) for 10 weeks or in combination with active- or inactive hyaluronidase infusion, given as protein/creatinin excretion ratio (µg/µg)

<p>Values are means ± SD from end-point urine samples. Difference in protein/creatinin rati... more <p>Values are means ± SD from end-point urine samples. Difference in protein/creatinin ratio was assessed by means of two-sample <i>t</i>-test (2-way). *<i>P</i><0.05 of <i>apoE<sup>−/−</sup></i> on HFC and inactive hyaluronidase vs. <i>apoE<sup>−/−</sup></i> on NC; **<i>P</i><0.05 of <i>apoE<sup>−/−</sup></i> on HFC and active hyaluronidase vs. <i>apoE<sup>−/−</sup></i> on NC or <i>apoE<sup>−/−</sup></i> on HFC and inactive hyaluronidase.</p

Research paper thumbnail of Glycocalyx, cardiometabolic disease and inflammation

De glycocalyx is een laag moleculen tussen het endotheel (de binnenbekleding van de bloedvaten) e... more De glycocalyx is een laag moleculen tussen het endotheel (de binnenbekleding van de bloedvaten) en het bloed. De glycocalyx zorgt ervoor dat er geen lekkage ontstaat en voorkomt dat bloedplaatjes en afweercellen vastplakken aan de vaatwand. Dit maakt de glycocalyx een interessant aangrijpingspunt voor nieuwe medicijnen tegen aderverkalking (atherosclerose). Vroege schade aan het endotheel kan atherosclerose versterken. Lysette Broekhuizen onderzocht

Research paper thumbnail of Cardiac magnetic resonance in advanced heart failure

Echocardiography, Jun 1, 2024

Research paper thumbnail of Serial Screening in a Young Athletic Male Carrier of Phospholamban R14 Deletion

Journal of cardiovascular magnetic resonance, 2024

Research paper thumbnail of Non-Invasive Assessment of Multivalvular Heart Disease: A Comprehensive Review

Reviews in Cardiovascular Medicine, Jan 15, 2024

Research paper thumbnail of Screening for coronary artery disease using primary evaluation with coronary CTA in aviation medicine (SUSPECT): study design

International Journal of Clinical Trials

Background: Sudden in-flight incapacitation of aircrew may cause an airplane crash. Important cau... more Background: Sudden in-flight incapacitation of aircrew may cause an airplane crash. Important causes are major adverse cardiac events, such as myocardial infarction and sudden cardiac arrest. Aircrew of the Royal Netherlands Air Force (RNLAF) are required to undergo periodic cardiac screening, including bicycle exercise-testing. Unfortunately, this modality lacks diagnostic accuracy for relevant coronary artery disease (CAD) in low-risk populations similar to military aircrew. Cardiac CT, however, comprising Coronary Artery Calcium score (CACS) and coronary CT angiography (CCTA), is able to adequately detect (subclinical) CAD with high negative predictive values in low-risk populations and may provide opportunity for early interventions. Methods: This was a prospective, single-center, cohort study of 250 military aircrew. Asymptomatic aircrew ≥40 years are asked to undergo a voluntary cardiac CT following routine aeromedical examination. Prevalence and severity of CAD will be descri...

Research paper thumbnail of Reduction of monocyte chemoattractant protein 1 and macrophage migration inhibitory factor by a polyphenol-rich extract in subjects with clustered cardiometabolic risk factors

British Journal of Nutrition, Jun 28, 2011

Research paper thumbnail of The association between the gene encoding 5-lipoxygenase activating protein and abdominal aortic aneurysms

Atherosclerosis, Feb 1, 2012

Research paper thumbnail of Left Atrio-ventricular Coupling Index as a Predictor of Diastolic Dysfunction in Patients After Myocardial Infarction

Journal of cardiovascular magnetic resonance, 2024

Research paper thumbnail of Effects of SUlodexide on damaged endothelial Glycocalyx in pAtients with diabetes Mellitus type two: Reversing damage

http://isrctn.org/>, 2012

Research paper thumbnail of The association between the 5-LipOxygenase pathway and abdominal aortic aneurysms

http://isrctn.org/>, 2012

Research paper thumbnail of The Role of Non-Invasive Multimodality Imaging in Chronic Coronary Syndrome: Anatomical and Functional Pathways

Diagnostics

Coronary artery disease (CAD) is one of the major causes of mortality and morbidity worldwide, wi... more Coronary artery disease (CAD) is one of the major causes of mortality and morbidity worldwide, with a high socioeconomic impact. Currently, various guidelines and recommendations have been published about chronic coronary syndromes (CCS). According to the recent European Society of Cardiology guidelines on chronic coronary syndrome, a multimodal imaging approach is strongly recommended in the evaluation of patients with suspected CAD. Today, in the current practice, non-invasive imaging methods can assess coronary anatomy through coronary computed tomography angiography (CCTA) and/or inducible myocardial ischemia through functional stress testing (stress echocardiography, cardiac magnetic resonance imaging, single photon emission computed tomography—SPECT, or positron emission tomography—PET). However, recent trials (ISCHEMIA and REVIVED) have cast doubt on the previous conception of the management of patients with CCS, and nowadays it is essential to understand the limitations and ...

Research paper thumbnail of Atherogenic progression in the innominate- (white bars) and left subclavian (black bars) artery from <i>apoE<sup>−/−</sup></i> mice on a combined Western-type atherogenic diet with inactive- or active hyaluronidase infusion

<p>(A) Distribution and level of advanced plaque areas, given µm<sup>2</sup> ×1... more <p>(A) Distribution and level of advanced plaque areas, given µm<sup>2</sup> ×10.000. Distribution and percentage of (B) collagen or (C) glycosaminoglycan within each plaque area. Distribution of individual macrophage areas within each plaque area (D), given in µm<sup>2</sup>.</p

Research paper thumbnail of Systemic parameters of <i>apoE<sup>−/−</sup></i> mice on NC or HFC for 6- or 10 weeks w/o a final 4 week hyaluronidase infusion

<p>Systemic parameters of <i>apoE<sup>−/−</sup></i> mice on NC or H... more <p>Systemic parameters of <i>apoE<sup>−/−</sup></i> mice on NC or HFC for 6- or 10 weeks w/o a final 4 week hyaluronidase infusion.</p

Research paper thumbnail of Photomicrographs of Sirius red-stained lesions within two major vessels branching from the aortic arch with a difference in onset of atherogenic development

<p>The (A, B, C) innominate- (early start) and (D, E, F) left subclavian artery (later star... more <p>The (A, B, C) innominate- (early start) and (D, E, F) left subclavian artery (later start) from <i>apoE<sup>−/−</sup></i> mice on (A, D) a Western-type atherogenic diet alone, or in combination with (B, E) inactive- or (C, F) active hyaluronidase infusion, (inset F) Higher magnification of Sirius red-stained lesion within the left subclavian artery from <i>apoE<sup>−/−</sup></i> mice on a combined Western-type atherogenic diet and active hyaluronidase infusion. Arrow head indicates absence of long stretches of the intimal layer underneath a plaque. Bar = 0.2 mm, bar inset = 50 µm.</p

Research paper thumbnail of Renal morphology in <i>apoE<sup>−/−</sup></i> mice on HFC for 10 weeks with a final 4 week hyaluronidase infusion

<p>Renal morphology in <i>apoE<sup>−/−</sup></i> mice on HFC for 10... more <p>Renal morphology in <i>apoE<sup>−/−</sup></i> mice on HFC for 10 weeks with a final 4 week hyaluronidase infusion.</p

Research paper thumbnail of Renal morphology of <i>periodic acid Schiff’s</i> stained (PAS) glomeruli of <i>apoE<sup>−/−</sup></i> mice on a combined Western-type atherogenic diet with (A) inactive- or (B)active hyaluronidase infusion

<p>Bar = 50 µm.</p

Research paper thumbnail of Endothelial Surface Layer Degradation by Chronic Hyaluronidase Infusion Induces Proteinuria in Apolipoprotein E-Deficient Mice

PLoS ONE, 2010

Objective: Functional studies show that disruption of endothelial surface layer (ESL) is accompan... more Objective: Functional studies show that disruption of endothelial surface layer (ESL) is accompanied by enhanced sensitivity of the vasculature towards atherogenic stimuli. However, relevance of ESL disruption as causal mechanism for vascular dysfunction remains to be demonstrated. We examined if loss of ESL through enzymatic degradation would affect vascular barrier properties in an atherogenic model. Methods: Eight week old male apolipoprotein E deficient mice on Western-type diet for 10 weeks received continuous active or heat-inactivated hyaluronidase (10 U/hr, i.v.) through an osmotic minipump during 4 weeks. Blood chemistry and anatomic changes in both macrovasculature and kidneys were examined. Results: Infusion with active hyaluronidase resulted in decreased ESL (0.3260.22 mL) and plasma volume (1.0360.18 mL) compared to inactivated hyaluronidase (0.5260.29 mL and 1.2860.08 mL, p,0.05 respectively).Active hyaluronidase increased proteinuria compared to inactive hyaluronidase (0.2760.02 vs. 0.1560.01 mg/mg protein/creatinin, p,0.05) without changes in glomerular morphology or development of tubulo-interstitial inflammation. Atherosclerotic lesions in the aortic branches showed increased matrix production (collagen, 3265 vs. 1863%; glycosaminoglycans, 1165 vs. 0.160.01%, active vs. inactive hyaluronidase, p,0.05). Conclusion: ESL degradation in apoE deficient mice contributes to reduced increased urinary protein excretion without significant changes in renal morphology. Second, the induction of compositional changes in atherogenic plaques by hyaluronidase point towards increased plaque vulnerability. These findings support further efforts to evaluate whether ESL restoration is a valuable target to prevent (micro) vascular disease progression.

Research paper thumbnail of Aortic regurgitation: A multimodality approach

Journal of Clinical Ultrasound

Research paper thumbnail of Sulfated glycosaminoglycans restore glycocalyx barrier properties of cultured endothelial cells in hyperglycemia

The FASEB Journal, 2008

Introduction: Microalbuminuria is a clinical parameter of vascular dysfunction in patients with d... more Introduction: Microalbuminuria is a clinical parameter of vascular dysfunction in patients with diabetes. The endothelial glycocalyx plays a role in regulation of vascular permeability. Therapeutic interventions using a mixture of glycosaminoglycans (GAGs) containing 80% heparin and 20% dermatan sulphate (sulodexide) have been shown to improve vascular barrier function by reducing microalbuminuria. Therefore we hypothesized that exogenous GAGs attenuate hyperglycemia-induced increases in endothelial permeability for albumin by restoring barrier properties of the endothelial glycocalyx. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured on semi-permeable inserts and exposed to normo-(5 mM) or hyperglycemia (25 mM) for 4 days, last 24 h in presence of the GAG mixture. Endothelial permeability was assessed by determining FITC-labeled albumin transfer over the monolayer (3 hours). Additionally, the glycocalyx glucosamine sugar residues on the endothelial cells were visualized with LEA-lectin staining. Results: Albumin permeability of endothelial cells under hyperglycemia was increased to 122 ± 8% (p < 0.01) compared to normoglycemia. Changes in albumin permeability under hyperglycemia normalized to normoglycemic control condition was-4 ± 3% (p < 0.05) in the presence of 0.06μg/mL sulodexide. Additionally, LEA-lectin revealed a 28 ± 1% (p < 0.05) increase in glucosamine staining in hyperglycemic cells in the presence of the GAG mix. Conclusion: GAG supplementation reverses the increased trans-endothelial albumin leakage under hyperglycemic conditions by restoring the barrier properties of the endothelial glycocalyx layer in vitro.

Research paper thumbnail of Renal protein leakage of <i>apoE<sup>−/−</sup></i> mice on normal chow (NC) or on a Western-type atherogenic diet (HFC) for 10 weeks or in combination with active- or inactive hyaluronidase infusion, given as protein/creatinin excretion ratio (µg/µg)

<p>Values are means ± SD from end-point urine samples. Difference in protein/creatinin rati... more <p>Values are means ± SD from end-point urine samples. Difference in protein/creatinin ratio was assessed by means of two-sample <i>t</i>-test (2-way). *<i>P</i><0.05 of <i>apoE<sup>−/−</sup></i> on HFC and inactive hyaluronidase vs. <i>apoE<sup>−/−</sup></i> on NC; **<i>P</i><0.05 of <i>apoE<sup>−/−</sup></i> on HFC and active hyaluronidase vs. <i>apoE<sup>−/−</sup></i> on NC or <i>apoE<sup>−/−</sup></i> on HFC and inactive hyaluronidase.</p

Research paper thumbnail of Glycocalyx, cardiometabolic disease and inflammation

De glycocalyx is een laag moleculen tussen het endotheel (de binnenbekleding van de bloedvaten) e... more De glycocalyx is een laag moleculen tussen het endotheel (de binnenbekleding van de bloedvaten) en het bloed. De glycocalyx zorgt ervoor dat er geen lekkage ontstaat en voorkomt dat bloedplaatjes en afweercellen vastplakken aan de vaatwand. Dit maakt de glycocalyx een interessant aangrijpingspunt voor nieuwe medicijnen tegen aderverkalking (atherosclerose). Vroege schade aan het endotheel kan atherosclerose versterken. Lysette Broekhuizen onderzocht