BackgroundAn aortic dissection is the most devastating complication of thoracic aortic disease. Several non- and syndromic conditions such as a bicuspid aortic valve (BAV) and Marfan syndrome (MFS)... Show moreBackgroundAn aortic dissection is the most devastating complication of thoracic aortic disease. Several non- and syndromic conditions such as a bicuspid aortic valve (BAV) and Marfan syndrome (MFS) have a severely increased risk to develop a thoracic aortic aneurysm and dissection. To date, the medial layer has been extensively studied in search of the pathogenetic mechanisms leading to aortic complications.ObjectiveWe aim to determine whether intimal layer pathology is characteristic in all thoracic aortopathy regardless of the underlying etiology.MethodA total of 176 aortic wall specimen were studied for the intimal layer architecture including the intimal thickness, endothelial cell morphology, and atherosclerosis. Specimens were derived from four patient groups: BAV (n = 70, age 57 ± 8.9 years), isolated tricuspid aortic valve (TAV) (n = 38, age 64.9 ± 11.0 years), MFS with a TAV (n = 8, age 34.2 ± 11.0 years), type A dissections with a TAV (n = 60, age 62.7 ± 10 years).ResultsThe intimal layer is significantly thinner in BAV, MFS, and type A aortic dissection as compared to the isolated TAV patients (p < 0.001). Intimal atherosclerosis was also significantly less present in the three groups as compared to the isolated TAV (p < 0.05).DiscussionA thin intimal layer is a common finding in the thoracic aortopathy patients. Studies aiming at preventing future aortic complications should focus on the intimal pathology as a common effector pathway in thoracic aortopathy. Show less
A bicuspid aortic valve (BAV) is the most prevalent congenital cardiac deformity, which is associated with an increased risk to develop a thoracic aortic aneurysm and/or an aortic dissection as... Show moreA bicuspid aortic valve (BAV) is the most prevalent congenital cardiac deformity, which is associated with an increased risk to develop a thoracic aortic aneurysm and/or an aortic dissection as compared to persons with a tricuspid aortic valve. Due to the high prevalence of a BAV in the general population and the associated life-long increased risk for adverse vascular events, BAV disease places a considerable burden on the public health. The aim of the present review is to discuss the role of transforming growth factor beta (TGF-ss) signaling in the development of the vascular wall and on how this complex signaling pathway may be involved in thoracic aortic aneurysm formation in tricuspid and BAV patients. Show less
Objective Bicuspid aortic valve (BAV) has been associated with less atherosclerosis as compared with tricuspid aortic valve (TAV) patients. It, however, remains unclear whether this reflects the... Show moreObjective Bicuspid aortic valve (BAV) has been associated with less atherosclerosis as compared with tricuspid aortic valve (TAV) patients. It, however, remains unclear whether this reflects the older age of TAV patients and/or accumulation of atherosclerotic risk factors or that the BAV phenotype is atheroprotective. Therefore, we compared the atherosclerotic disease burden of BAV and TAV patients, with that of the general (age-matched) population.Methods The prevalence of coronary artery disease (CAD) and CAD risk factors in BAV and TAV patients who underwent aortic valve surgery were compared with the Dutch general practitioners registry data. BAV (n=454) and TAV (n=1101) patients were divided into four groups: BAV with aortic valve stenosis (BAV-AoS), BAV with aortic valve regurgitation (BAV-AR), TAV with AoS (TAV-AoS) and TAV with AR (TAV-AR). The atherosclerotic disease burden of each group was compared with that of the corresponding age cohort for the general population.Results CAD risk factors hypertension and hypercholesterolaemia were more prevalent in the surgery groups than the age-matched general population (all p<0.001). All BAVs (BAV-AoS and BAV-AR) and TAV-AR had a similar incidence of CAD history as compared to the age-matched general populations (p=0.689, p=0.325 and p=0.617 respectively), whereas TAV-AoS had a higher incidence (21.6% versus 14.9% in the age-matched general population, p<0.001).Conclusions Stenotic TAV disease is part of the atherosclerotic disease spectrum, while regurgitant TAV and all BAVs are not. Although the prevalence of cardiovascular risk factors is higher in all BAV patients, the prevalence of CAD is similar to the general population. Show less
(1) Background: The pathophysiologic basis of an acute type A aortic dissection (TAAD) is largely unknown. In an effort to evaluate vessel wall defects, we systematically studied aortic specimens... Show more(1) Background: The pathophysiologic basis of an acute type A aortic dissection (TAAD) is largely unknown. In an effort to evaluate vessel wall defects, we systematically studied aortic specimens in TAAD patients. (2) Methods: Ascending aortic wall specimens (n = 58, mean age 63 years) with TAAD were collected. Autopsy tissues (n = 17, mean age 63 years) served as controls. All sections were studied histopathologically. (3) Results: Pathomorphology in TAAD showed predominantly moderate elastic fiber fragmentation/loss, elastic fiber thinning, elastic fiber degeneration, mucoid extracellular matrix accumulation, smooth muscle cell nuclei loss, and overall medial degeneration. The control group showed significantly fewer signs of those histopathological features (none-mild, p = 0.00). It was concluded that the dissection plane consistently coincides with the vasa vasorum network, and that TAAD associates with a significantly thinner intimal layer p = 0.005). (4) Conclusions: On the basis of the systematic evaluation and the consistent presence of diffuse, pre-existing medial defects, we hypothesize that TAAD relates to a developmental defect of the ascending aorta and is caused by a triple-hit mechanism that involves (I) an intimal tear; and (II) a diseased media, which allows (III) propagation of the tear towards the plane of the vasa vasorum where the dissection further progresses. Show less
Boekhorst, B.C.M.T.; Bovens, S.M.; Kolk, C.W.A. van de; Cramer, M.J.M.; Doevendans, P.A.F.M.; Hove, M. ten; ... ; Echteld, C.J.A. van 2010
Single fast spin echo scans covering limited time frames are mostly used for contrast-enhanced MRI of atherosclerotic plaque biomarkers. Knowledge on inter-scan variability of the normalized... Show moreSingle fast spin echo scans covering limited time frames are mostly used for contrast-enhanced MRI of atherosclerotic plaque biomarkers. Knowledge on inter-scan variability of the normalized enhancement ratio of plaque (NERplaque) and relation between NERplaque and gadolinium content for inversion-recovery fast spin echo is limited. Study aims were: evaluation of (1) timing of MRI after intravenous injection of Cannabinoid-2 receptor (CB2-R) (expressed by human and mouse plaque macrophages) targeted micelles; (2) inter-scan variability of inversion-recovery fast spin echo and fast spin echo; (3) relation between NERplaque and gadolinium content for inversion-recovery fast spin echo and fast spin echo. Inversion-recovery fast spin echo/fast spin echo imaging was performed before and every 15 min up to 48 h after injection of CB2-R targeted or control micelles using several groups of mice measured in an interleaved fashion. NERplaque (determined on inversion-recovery fast spin echo images) remained high (similar to 2) until 48 h after injection of CB2-R targeted micelles, whereas NERplaque decreased after 36 h in the control group. The inter-scan variability and relation between NERplaque and gadolinium (assessed with inductively coupled plasma- mass spectrometry) were compared between inversion-recovery fast spin echo and fast spin echo. Inter-scan variability was higher for inversion-recovery fast spin echo than for fast spin echo. Although gadolinium and NERplaque correlated well for both techniques, the NER of plaque was higher for inversion-recovery fast spin echo than for fast spin echo. In mice injected with CB2-R targeted micelles, NERplaque can be best evaluated at 36-48 h post-injection. Because NERplaque was higher for inversion-recovery fast spin echo than for fast spin echo, but with high inter-scan variability, repeated inversion-recovery fast spin echo imaging and averaging of the obtained NERplaque values is recommended. Copyright (c) 2010 John Wiley & Sons, Ltd. Show less
