Biomedical subjects

Michiel Knaapen

Publications and source records attributed to Michiel Knaapen.

10 recordsLinked to original sources

PubMed2006

Histopathology of calcific aortic valve stenosis.

Calcific aortic valve stenosis is the most common and increasing heart valve disease in the western world. In the last 30 years, diagnosis and management were revolutionized by the development of cardiac catheterisation, echocardiography, cardiac surgery, and medication. Recently, new strategies were introduced for aortic valve replacement using more sophisticated bioprosthetic heart valves. Moreover, tissue-engineered heart valves are under development to improve management strategies. In this article we review the current morphological and histopathological findings in the progression of calcific aortic valve stenosis. This is, to our understanding, important to contribute to the knowledge of fundamental management strategies of this disease.

Aortic Valve Stenosis↗

PubMed2006

Histological evaluation of autophagic cell death in calcified aortic valve stenosis.

BACKGROUND AND AIM OF THE STUDY: Calcification in aortic valves is the most common valvular lesion in western populations. This event is correlated with cellular degeneration in the valvular cusps, although there is no exact evidence how these cells die: this requires further exploration. METHODS: Twelve human severely calcified aortic valves obtained during cardiac surgery were studied by semi-quantitative analysis, and results compared with data from 12 human control aortic valves obtained during autopsy. Tissue analysis was by hematoxylin and eosin and Alcian blue staining. Detection of neurons was by immunohistochemical staining of PGP9.5 and neurofilament. In order to detect autophagy, an immunohistochemical staining for ubiquitin was used. The TUNEL technique was used to detect apoptosis. Co-localization of Alizarin red with ubiquitin labeling was performed on non-decalcified aortic valves. RESULTS: Hematoxylin and eosin staining showed moderate to severe mineralization in 10 of 12 patients in the surgical group, but in only one of 12 in the autopsy group. No significant observations were made with regard to PGP9.5 and neurofilament staining. Moderate to severe ubiquitin labeling was found initially in the majority of the surgical resection group (9/12) compared to a minority in the autopsy group (1/12). TUNEL-positive labeling was very rare and found mostly at the endothelial layer of the valvular cusps. CONCLUSION: Immunohistochemical methods showed the main cell death mechanism involved in the calcification of aortic leaflets to be autophagy rather than apoptosis. These findings suggest that autophagic cell death might play a role in the release of matrix vesicles in early degenerative aortic valves, thereby attracting inflammatory cells, and this could eventually lead to mineralization.

Aged↗

PubMed2005

Influence of intracoronary attenuation on coronary plaque measurements using multislice computed tomography: observations in an ex vivo model of coronary computed tomography angiography.

Assessment of attenuation (measured in Hounsfield units, HU) of human coronary plaques was performed using multislice computed tomography (MSCT) in an ex vivo model. In three ex vivo specimens of left coronary arteries in oil, MSCT was performed after intracoronary injection of four solutions of contrast material (400 mgI/ml iomeprol). The four solutions were diluted as follows: 1/infinity, 1/200, 1/80, and 1/20. All scans were performed with the following parameters: slices/collimation 16/0.75 mm, rotation time 375 ms. Each specimen was scored for the presence of atherosclerotic plaques. In each plaque the attenuation was measured in four regions of interest for lumen, plaque (non-calcified thickening of the vessel wall), calcium, and surrounding (oil surrounding the vessel). The results were compared with a one-way analysis of variance test and were correlated with Pearson's test. There were no significant differences in the attenuation of calcium and oil in the four solutions. The mean attenuation in the four solutions for lumen (35+/-10, 91+/-7, 246+/-18, 511+/-89 HU) and plaque (22+/-22, 50+/-26, 107+/-36, 152+/-67 HU) was significantly different between each decreasing dilution (p<0.001). The mean attenuation of lumen and plaque of coronary plaques showed high correlation, while the values were significantly different (r=0.73; p<0.001). Intracoronary attenuation modifies significantly the attenuation of plaques assessed with MSCT.

Cadaver↗

PubMed2005

Influence of increasing convolution kernel filtering on plaque imaging with multislice CT using an ex-vivo model of coronary angiography.

PURPOSE: To assess the variability in attenuation of coronary plaques with multislice CT-angiography (MSCT-CA) in an ex-vivo model with varying convolution kernels. MATERIALS AND METHODS: MSCT-CA (Sensation 16, Siemens) was performed in three ex-vivo left coronary arteries after instillation of contrast material solution (Iomeprol 400 mgI/ml, dilution: 1/80). The specimens were placed in oil to simulate epicardial fat. Scan parameters: slices 16/0.75 mm, rotation time 375 ms, feed/rotation 3.0 mm, mAs 500, slice thickness 1 mm, and FOV 50 mm. Datasets were reconstructed using 4 different kernels (B30f-smooth, B36f-medium smooth, B46f-medium, and B60f-sharp). Each scan was scored for the presence of plaques. Once a plaque was detected, the operator performed attenuation measurements (HU) in coronary lumen, oil, calcified and soft plaque tissue using the same settings in all datasets. The results were compared with T-test and correlated with Pearson's test. RESULTS: Overall, 464 measurements were performed. Significant differences (p<0.05) were found for the mean attenuation of lumen (B30f/B36f, B30f/B60f, B36f/B46f, B36f/B60f, and B46f/B60f), oil (B30f/B36f, B30f/B46f, B30f/B60f, B36f/B46f, and B46f/B60f), calcium (all kernels), and plaque (B30f/B36f, B30f/B46f, B30f/B60f, and B46f/B60f) using 4 different kernels. The attenuation values (mean+/-SD) within the lumen (246+/-6, 215+/-13, 248+/-5, and 270+/-7), oil (-123+/-3, -127+/-1, -121+/-6, and -127+/-4), calcified plaque tissue (703+/-334, 739+/-364, 817+/-381, and 1181+/-503), and soft plaque tissue (134+/-56, 111+/-49, 120+/-56, and 102+/-41) showed high correlation (p<0.001) when attenuation of all structures were compared in different kernels. CONCLUSIONS: Use of sharper convolution kernels significantly increases the attenuation of the calcium within coronary plaques and reduces the attenuation of soft plaque tissue.

Aged↗

PubMed2004

Hemodynamic effects of inducible nitric oxide synthase and nitrotyrosine generation in heart failure.

OBJECTIVES: The hemodynamic effects of cardiac inducible nitric oxide synthase (iNOS) and of iNOS-mediated peroxynitrite in patients with left ventricular (LV) dysfunction are unclear. The present study investigates the incidence and functional significance of iNOS expression and nitrotyrosine formation in patients with heart failure. METHODS: LV endomyocardial biopsies obtained from 24 patients with heart failure due to idiopathic dilated cardiomyopathy (ejection fraction [EF] <45% and left ventricular end-diastolic volume index [LVEDVI] >102 ml/m2) were analyzed for iNOS and nitrotyrosine. LV contractile performance was assessed by left ventricular ejection fraction (LVEF) and stroke work normalized for end-diastolic pressure (SW/EDP). LV filling pattern was assessed by Doppler E/A wave ratio, deceleration time (DT) of early LV filling and indexed LV end-diastolic volume normalized for EDP as a marker of diastolic distensibility. RESULTS: iNOS immunostaining correlated significantly with nitrotyrosine formation (r = 0.86, p < 0.001). In the whole study group, patients expressing iNOS (n = 13) showed larger LV end-diastolic (173 +/-16 vs 128 +/- 9 ml/m2, p = 0.031) and end-systolic volume indices (110 +/- 16 vs 61 +/- 9 ml/m2, p = 0.018) and similar LVEDP (18 +/- 2 vs 21 +/- 2 mm Hg, p = 0.227). In patients with advanced heart failure and reduced pre-load reserve (LVEDP > 16 mm Hg, n = 18), iNOS protein and nitrotyrosine formation correlated positively with LVSW/EDP (r = 0.65, p = 0.03 and r = 0.64, p = 0.04, respectively), DT (r = 0.96, p < 0.01 and r = 0.88, p < 0.01, respectively) and inversely with E/A (r = -0.82, p < 0.01 and r = -0.88, p < 0.01, respectively). In addition, nitrotyrosine formation correlated positively with LVEDVI/EDP (r = 0.64, p = 0.02). Advanced iNOS-positive heart failure patients had a higher LVEDVI/EDP compared with iNOS-negative patients (5.30 +/- 0.64 vs 3.13 +/- 0.34 ml/mm Hg x m2, p = 0.02). CONCLUSIONS: In heart failure, iNOS protein expression is associated with nitrotyrosine formation. Although iNOS-positive patients are generally characterized by larger LV volume and depressed function, the preserved NO generation appears to be associated with higher cardiac work due to the preserved Frank-Starling relationship in end-stage heart failure.

Adult↗

PubMed2004

Vitamin D3 induces caspase-14 expression in psoriatic lesions and enhances caspase-14 processing in organotypic skin cultures.

Caspase-14 is a nonapoptotic caspase family member whose expression in the epidermis is confined to the suprabasal layers, which consist of differentiating keratinocytes. Proteolytic activation of this caspase is observed in the later stages of epidermal differentiation. In psoriatic skin, a dramatic decrease in caspase-14 expression in the parakeratotic plugs was observed. Topical treatment of psoriatic lesions with a vitamin D3 analogue resulted in a decrease of the psoriatic phenotype and an increase in caspase-14 expression in the parakeratotic plugs. To investigate whether vitamin D3 directly affects caspase-14 expression levels, we used keratinocyte cell cultures. 1alpha,25-Dihydroxycholecalciferol, the biologically active form of vitamin D3, increased caspase-14 expression, whereas retinoic acid inhibited it. Moreover, retinoic acid repressed the vitamin D3-induced caspase-14 expression level. In addition, the use of organotypic skin cultures demonstrated that 1alpha,25-dihydroxycholecalciferol enhanced epidermal differentiation and caspase-14 activation, whereas retinoic acid completely blocked caspase-14 processing. Our data indicate that caspase-14 plays an important role in terminal epidermal differentiation, and its absence may contribute to the psoriatic phenotype.

Adolescent↗

PubMed2004

Histopathologic evaluation of a novel-design nitinol stent: the Biflex stent.

BACKGROUND: Optimalization and improvement in stent material, stent design and deployment may alleviate the problem of restenosis after stenting. The Biflex stent is a novel-design stent made of nitinol; the vascular response after deployment in rabbit iliac arteries was evaluated. METHODS AND RESULTS: Normocholesterolemic New Zealand white rabbits (n = 8) were used. Iliac arteries were randomized to receive either a stainless steel control stent or a nitinol stent and rabbits were euthanized at 30 days after implantation. All animals survived and there were no adverse events. Vessels were harvested and prepared for histopathologic analysis and histomorphometry. Stents were well opposed to the vessel wall and thrombi were absent. The lumen area and the area within the internal elastic lamina were significantly larger in the nitinol stent group as opposed to the control group (3.8 +/- 0.1 vs 3.3 +/- 0.1 mm, p = 0.009 and 4.6 +/- 0.1 vs 4.1 +/- 0.2 mm, p = 0.03, respectively). There were no differences in injury score, neointimal area, medial area, area within the external elastic lamina and amount of inflammatory cells. Staining for alpha-smooth muscle cell actin and endothelium did not show any differences between the two groups as assessed semiquantitatively. CONCLUSION: This nitinol stent with a novel design demonstrated acceptable biocompatibility in iliac arteries of normocholesterolemic rabbits with minimal foreign-body reaction and minimal neointimal formation.

Alloys↗

PubMed2003

Human granulosa cells after ovulation induction show caspase-independent cell death.

It has become clear that apoptosis is an essential part of normal folliculogenesis and that granulosa cells in particular demonstrate intense cellular activity as well as programmed cell death. Although the entire mechanism of apoptosis appears to be conserved through many species, it now becomes clear that different cells may use different pathways within this system. We examined human granulosa cells after ovulation induction during an in vitro fertilization procedure to study apoptosis in this particular situation. We demonstrated a loss of cytokeratin staining as granulosa cells differentiate. We also detected that granulosa cells with apoptotic morphology did not stain for terminal deoxy-UTP nick end labeling and we showed the absence of immunoreactivity for caspase-cleaved cytokeratin, caspase-cleaved poly-ADP-ribose polymerase and caspase-cleaved caspase-3 in apoptotic granulosa cells. These data provide strong arguments for a caspase-independent cell death mechanism in human granulosa-lutein cells.

Apoptosis↗

PubMed2002

Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs.

OBJECTIVE: To study the effect of dietary cholesterol withdrawal on size and composition of LDL-hypercholesterolemia-induced coronary plaques in miniature pigs. METHODS: Pigs were on normal chow (control group), on a cholesterol-rich diet for 37 weeks (hypercholesterolemic group) or on a cholesterol-rich diet followed by normal chow for 26 weeks (cholesterol withdrawal group). Endothelial function was assessed with quantitative angiography after intracoronary infusion of acetylcholine, plaque load with intra-coronary ultrasound and plaque composition with image analysis of cross-sections. The effect of porcine serum on coronary smooth muscle cell (SMC) function was studied in vitro. RESULTS: Cholesterol-rich diet caused LDL-hypercholesterolemia, increased plasma levels of oxidized LDL (ox-LDL) and C-reactive protein (CRP), and induced endothelial dysfunction and coronary atherosclerosis. Dietary cholesterol withdrawal lowered LDL, ox-LDL and CRP. It restored endothelial function, did not affect plaque size but decreased lipid, ox-LDL and macrophage content. Smooth muscle cells and collagen accumulated within the plaque. Increased smoothelin-to-alpha-smooth muscle actin ratio indicated a more differentiated SMC phenotype. Cholesterol lowering reduced proliferation and apoptosis. In vitro, hypercholesterolemic serum increased SMC apoptosis and decreased SMC migration compared to non-hypercholesterolemic serum. CONCLUSIONS: Cholesterol lowering induced coronary plaque stabilization as evidenced by a decrease in lipids, ox-LDL, macrophages, apoptosis and cell proliferation, and an increase in differentiated SMC and collagen. Increased migration and decreased apoptosis of SMC may contribute to the disappearance of the a-cellular core after lipid lowering.

Acetylcholine↗

PubMedDate not supplied

The histopathology of varicose vein disease.

Varicosity is a complex venous pathology affecting the lower extremities. The exact etiology and physiopathology of varicose vein disease remain, however, unclear. Several theories exist from incompetence of the valves to a disturbance of the smooth muscle cells (SMC) and extra-cellular matrix (ECM) organization providing a weakness of the venous wall. Multiple studies have been performed to explain the underlying mechanisms of varicosity inducing alterations in the expression patterns of the endothelium, SMC, and ECM. In that respect, most attention has been focused on the alteration of the endothelium due to blood stasis and hypoxia inducing migration/proliferation of the medial SMC into the intima. Also, studies in the deformation of the ECM induced by alterations of the expression patterns of the metalloproteinases (MMP) and their inhibitors (TIMPs) have been put forward to explain the etiology of varicosity. However, less attention has been paid to the hormonal changes that occur during pregnancy and menopause, crucial factors to be involved in the etiology of varicosity. Since alteration of the estrogen receptor-b (ERb) expression could enhance directly the cellular volume of SMC and thus the disorganization of the contractile-elastic units, hypertrophy of SMC must be accounted a pivotal role that could induce the weakness of the venous wall. Altogether, this review summarizes an overview of the latest findings of varicosity with respect to the histopathological changes of the different cellular components of the varicose vein wall related to functional and morphologic alterations.

Endothelium, Vascular↗