A theoretical model for fibroblast-controlled growth of saccular cerebral aneurysms

A new theoretical model for the growth of saccular cerebral aneurysms is proposed by extending the recent constitutive framework of Kroon and Holzapfel [2007a. A model for saccular cerebral aneurysm growth by collagen fibre remodelling. J. Theor. Biol. 247, 775-787]. The continuous turnover of collagen is taken to be the driving mechanism in aneurysmal growth. The collagen production rate depends on the magnitude of the cyclic deformation of fibroblasts, caused by the pulsating blood pressure during the cardiac cycle. The volume density of fibroblasts in the aneurysmal tissue is taken to be constant throughout the growth process. The growth model is assessed by considering the inflation of an axisymmetric membranous piece of aneurysmal tissue, with material characteristics representative of a cerebral aneurysm. The diastolic and systolic states of the aneurysm are computed, together with its load-free state. It turns out that the value of collagen pre-stretch, that determines growth speed and stability of the aneurysm, is of pivotal importance. The model is able to predict aneurysms with typical berry-like shapes observed clinically, and the predicted wall stresses correlate well with the experimentally obtained ultimate stresses of this type of tissue. The model predicts that aneurysms should fail when reaching a size of about 1.2-3.6 mm, which is smaller than what has been clinically observed. With some refinements, the model may, however, be used to predict future growth of diagnosed aneurysms.     

Vasomotion: the case for chaos

Fluctuations in vascular calibre, a phenomenon known as vasomotion, are ubiquitous in the microcirculation and represent emergent behaviour that involves synchronisation of Ca²⁺ oscillations in individual vascular cells. Ideally, coordinated interactions between locally generated vasomotion and neuro-humoral control mechanisms will allow optimal sensing of flow and pressure within vascular networks and thereby facilitate synergistic readjustments in local vascular conductance and flow under conditions of dynamically changing metabolic demand. Indeed, many studies have reported that vasomotion becomes more prominent under pathophysiological conditions, suggesting that it may serve as an adaptive homeodynamic response that maintains or re-establishes flow when perfusion is compromised. We here summarise evidence that the apparent irregular nature of vasomotion reflects deterministic interactions between a small number of dominant control variables, rather than random events, and may therefore be formally classified as chaotic. We also discuss the potential physiological benefits of chaos in the microcirculation and the key roles of signalling via gap junctions and nitric oxide.     

Blocking Interferon β Stimulates Vascular Smooth Muscle Cell Proliferation and Arteriogenesis

Increased interferon (IFN)-β signaling in patients with insufficient coronary collateralization and an inhibitory effect of IFNβ on collateral artery growth in mice have been reported. The mechanisms of IFNβ-induced inhibition of arteriogenesis are unknown. In stimulated monocytes from patients with chronic total coronary artery occlusion and decreased arteriogenic response, whole genome expression analysis showed increased expression of IFNβ-regulated genes. Immunohistochemically, the IFNβ receptor was localized in the vascular media of murine collateral arteries. Treatment of vascular smooth muscle cells (VSMC) with IFNβ resulted in an attenuated proliferation, cell-cycle arrest, and increased expression of cyclin-dependent kinase inhibitor-1A (p21). The growth inhibitory effect of IFNβ was attenuated by inhibition of p21 by RNA interference. IFNβ-treated THP1 monocytes showed enhanced apoptosis. Subsequently, we tested if collateral artery growth can be stimulated by inhibition of IFNβ-signaling. RNA interference of the IFNβ receptor-1 (IFNAR1) increased VSMC proliferation, cell cycle progression, and reduced p21 gene expression. IFNβ signaling and FAS and TRAIL expression were attenuated in monocytes from IFNAR1^−/− mice, indicating reduced monocyte apoptosis. Hindlimb perfusion restoration 1 week after femoral artery ligation was improved in IFNAR1^−/− mice compared with wild-type mice as assessed by infusion of fluorescent microspheres. These results demonstrate that IFNβ inhibits collateral artery growth and VSMC proliferation through p21-dependent cell cycle arrest and induction of monocyte apoptosis. Inhibition of IFNβ stimulates VSMC proliferation and collateral artery growth.     

One-year clinical follow-up of a registry evaluating a percutaneous revascularisation strategy combining a pre-specified simple selection process with the use of a new thin-strut bare cobalt-chromium stent

Objectives. To evaluate clinical events in a specifically selected cohort of patients with obstructive coronary artery disease (CAD), using a new generation thin-strut bare cobalt-chromium coronary stent. Methods. Patients with single- or multi-vessel, stable or unstable CAD eligible for percutaneous implantation of at least one bare cobalt-chromium stent were evaluated in a single-centre registry. Prospective pre-specified criteria for bare cobalt-chromium stent implantation in our centre were: any acute ST-elevation myocardial infarction (MI), otherwise 1) de novo coronary lesion, and 2) lesion length <20 mm, and 3) reference vessel diameter >2.6 mm, and 4) no diabetes, unless reference vessel diameter >3.5 mm. Endpoints, retrospectively collected, were death, MI and clinically driven target-lesion revascularisation (TLR) and target-vessel revascularisation (TVR) after 12 months. Results. Between September 2005 and June 2007, 712 patients (48.7% one-vessel, 29.9% two-vessel, 20% three-vessel and 1.4% left main disease; 7.9% diabetics) were treated with 800 bare cobalt-chromium stents, for stable angina (40.9%), unstable angina (20.9%) or acute ST-elevation MI (38.2%). The procedural success rate was 99.3%. Peri-procedural MI rate was 2.2% in the semi-elective group. At 12 months there were 17 deaths (2.4%), of which nine non-cardiac, 20 (2.8%) MI, 19 (2.7%) TLR and 29 (4.1%) TVR. Early and late definite stent thrombosis occurred in four (0.6%) and three (0.4%) patients, respectively. Conclusion. A strategy aimed at minimising drug-eluting stent use and combining a pre-specified simple selection process with the use of a new thin-strut bare cobalt-chromium stent is safe and effective at one-year clinical follow-up. (Neth Heart J 2010;18:486-92.)     

Design of compliance chamber and after-load in apparatus for cultured endothelial cells subjected to stresses

In order to create a hemodynamic environment that can simulate the physiological condition of arteries, an in vitro experiment apparatus was designed whose key modules were compliance chamber and after-load. These two modules were developed based on the theories of hemodynamics. Both the normal and shear stress to which endothelial cells are exposed can be controlled with these modules, thus facilitating the research of endothelial cells subjected to stresses.     

Hypertrophy of radial and ulnar arteries following denervation of the chicken wing

Summary Denervation of radial and ulnar arteries in the growing and adult domestic fowl was achieved by unilateral sectioning of the brachial plexus. Eight weeks later the denervated arteries and those of the contralateral wing were examined with light- and electron microscopy to determine the effect of denervation on arterial structure.In growing fowls, the area of the media in radial and ulnar arteries was increased by 29% and 25%, respectively, after denervation. The number of smooth muscle layers was also significantly increased by 16% (radial) and 14% (ulnar), but no significant variation was seen in the wall/lumen ratio of either growing artery. In adult fowls, the area of the media was increased by 93% (radial) and 32% (ulnar) following denervation and the number of smooth muscle cell layers increased by 39% (radial) and 11% (ulnar). There was also an increased wall/lumen ratio of 64% (radial) and 92% (ulnar).These results indicate that hyperplasia of smooth muscle has occurred in response to denervation. Flow-cytometric DNA analysis of growing arteries also indicates that the increase in muscle-cell volume is a result of cell division (not polyploidy) since no significant differences were found between the control and denervated arteries in any stages of the cell cycle.     

Ephrin-B2 reverse signaling is required for axon pathfinding and cardiac valve formation but not early vascular development

Vascular development begins with the formation of a primary vascular plexus that is rapidly remodeled by angiogenesis into the interconnected branched patterns characteristic of mature vasculature. Several receptor tyrosine kinases and their ligands have been implicated to control early development of the vascular system. These include the vascular endothelial growth factor receptors (VEGFR-1 and VEGFR-2) that bind VEGF, the Tie-1 and Tie-2 receptors that bind the angiopoietins, and the EphB4 receptor that binds the membrane-anchored ligand ephrin-B2. Targeted mutations in the mouse germline have revealed essential functions for these molecules in vascular development. In particular, protein-null mutations that delete either EphB4 or ephrin-B2 from the mouse have been shown to result in early embryonic lethality due to failed angiogenic remodeling. The venous expression of EphB4 and arterial expression of ephrin-B2 has lead to the speculation that the interaction of these two molecules leads to bidirectional signaling into both the receptor-expressing cell and the ligand-expressing cell, and that both forward and reverse signals are required for proper development of blood vessels in the embryo. Indeed, targeted removal of the ephrin-B2 carboxy-terminal cytoplasmic tail by another group was shown to perturb vascular development and result in the same early embryonic lethality as the null mutation, leading the authors to propose that ephrin-B2 reverse signaling directs early angiogenic remodeling of the primary vascular plexus [Cell 104 (2001) 57]. However, we show here that the carboxy-terminal cytoplasmic domain of ephrin-B2, and hence reverse signaling, is not required during early vascular development, but it is necessary for neonatal survival and functions later in cardiovascular development in the maturation of cardiac valve leaflets. We further show that ephrin-B2 reverse signaling is required for the pathfinding of axons that form the posterior tract of the anterior commissure. Our results thus indicate that ephrin-B2 functions in the early embryo as a typical instructive ligand to stimulate EphB4 receptor forward signaling during angiogenic remodeling and that later in embryonic development ephrin-B2 functions as a receptor to transduce reverse signals involved in cardiac valve maturation and axon pathfinding.     

Accumulation of calcium in human common iliac artery, aortic valve, xiphoid process, costal cartilage, posterior longitudinal ligament, trigeminal nerve, and rib accompanied by increase of magnesium

To examine whether an accumulation of Ca in the tissues was accompanied by an increase of Mg, the authros investigated the relationships between Ca and Mg contents in the common iliac arteries, aortic valves, xiphoid processes, costal cartilages, posterior longitudinal ligaments, trigeminal nerves, and ribs by inductively coupled plasma-atomic emission spectrometry. After the ordinary dissections by medical students were finished, the common iliac arteries, aortic valves, xiphoid processes, bilateral the fourth costal cartilages, posterior longitudinal ligaments between the fourth and fifth cervical vertebrae, trigeminal nerves, and bilateral the sixth ribs were resected from the subjects and elements were determined. It was found that there were extremely significant direct correlations between Ca and Mg contents in all of the common iliac arteries, aortic valves, costal cartilages, posterior longitudinal ligaments, and trigeminal nerves, whereas there were significant direct correlations in both the xiphoid processes and ribs. As for the tissues containing Ca higher than 20 mg/g, the average mass ratios of Mg/Ca were similar among the seven tissues. As Ca increased in all of the common iliac arteries, aortic valves, xiphoid processes, costal cartilages, posterior longitudinal ligaments, trigeminal nerves, and ribs, Mg increased simultaneously in the seven tissues.     

A computational model for collagen fibre remodelling in the arterial wall

As the interaction between tissue adaptation and the mechanical condition within tissues is complex, mathematical models are desired to study this interrelation. In this study, a mathematical model is presented to investigate the interplay between collagen architecture and mechanical loading conditions in the arterial wall. It is assumed that the collagen fibres align along preferred directions, situated in between the principal stretch directions. The predicted fibre directions represent symmetrically arranged helices and agree qualitatively with morphometric data from literature. At the luminal side of the arterial wall, the fibres are oriented more circumferentially than at the outer side. The discrete transition of the fibre orientation at the media-adventitia interface can be explained by accounting for the different reference configurations of both layers. The predicted pressure-radius relations resemble experimentally measured sigma-shaped curves. As there is a strong coupling between the collagen architecture and the mechanical loading condition within the tissue, we expect that the presented model for collagen remodelling is useful to gain further insight into the processes involved in vascular adaptation, such as growth and smooth muscle tone adaptation.