Chronic unilateral arm lymphedema correlates with increased intima-media thickness in the brachial artery

Summary: Drainage of the arterial wall via adventitial lymphatic vessels has been shown to play a pivotal role for vessel wall homeostasis. Also, retrograde cholesterol transport is ensured via this route, but no studies exist to demonstrate that lymphatic stasis would represent a mechanism to initiate atherosclerotic lesion formation in human arteries. To test this hypothesis, we embarked on a simple clinical experiment, assessing wall thickness in limb arteries with lymphedema after surgical intervention, with the contralateral limb serving as control. Using ultrasound imaging, the differential thickness was assessed separately for the three arterial wall layers. The potential of disease progression by lymphostasis was addressed by depiction of longitudinal results according to the time after lymph dissection.

Experimental Investigation of the Effects of Arterial Geometries in Different Severities of Symmetrical Stenosis on Pressure Drop and Pump Power

Biomedical studies is among the multidisciplinary studies attracting most interest in recent years. Blood and vessel interactions and consequent hemodynamic effects cause cardiovascular diseases. A testing setup constituted by a peristaltic pump (similar to the heart mechanism) system was installed. The purpose of the experimental study presented is to investigate the effect, pressure drop, peristaltic pump inlet and outlet pressure and most importantly, the amount of power consumed by the peristaltic pump regarding arterial stenosis severity with varying areal stenosis percentages. The tests were performed for the pulse values from 54 to 168 bpm by setting up models with 0%, 60%, 70% and 80% symmetrical stenosis severities. In the study, the pressure difference in the test area increased concomitantly with elevated pulse value and increased stenosis severity. This situation revealed that as the intensity of narrowing increases in vessels, the narrowing space differential pressure increases, and this amount increases even more with increased exertion. The pressure at the peristaltic pump outlet increased concomitantly with elevated pulse value and increased stenosis severity. The peristaltic pump overworked to overcome the increased differential pressure related to the increased pulse value and stenosis severity. This result of the experimental data reveals the necessity to avoid activities requiring high pulse in human arteries similarly with a high percentage of stenosis.

The cavernous carotid inferolateral trunk and persistent primitive maxillary arteries: analysis of dissected arterially injected fetal specimens and high-resolution micro-CT of the dog’s anastomotic arteries

Purpose The presence of a persistent primitive maxillary artery is described in the literature dealing with the development of the cavernous carotid inferolateral trunk, and the relevant similarities of the cranial circulation of the human and dog. The literature includes no dissection photographs of the above-mentioned two human fetal arteries, only diagrammatic representations. This study’s objectives were to analyze photographs of fetal dissections for the presence of these two arteries, and also investigate the possibility of obtaining, in preserved dog specimens, high-resolution micro-CT imaging of arteries homologous with the above-mentioned two human arteries. Methods The literature describing the embryologic development of the cavernous carotid inferolateral trunk, the persistent primitive maxillary arteries, and their homologies in the dog was reviewed. Relevant dissections of fetal specimens were analyzed. High-resolution micro-CT images of un-dissected dog arteries were produced and analyzed. Results Photographs of fetal specimen dissections demonstrate the cavernous carotid inferolateral trunk. A separate persistent primitive maxillary artery was not present in the dissected specimens. High-resolution micro-CT images of the dog demonstrate homologous arteries with segments of the human inferolateral trunk, and other skull base and brain arteries. Conclusion This investigation provides the only photographs in the literature of dissected human fetal cavernous carotid inferolateral trunks. A persistent primitive maxillary artery was not present in the dissected specimens and is a non-existent structure, likely a previously misidentified carotid inferolateral trunk. High-resolution micro-CT images of the dog visualized arteries that are homologous to segments of the human cavernous carotid inferolateral trunk artery.

Confocal Blood Flow Videomicroscopy of Thrombus Formation over Human Arteries and Local Targeting of P2X7

Atherothrombosis exposes vascular components to blood. Currently, new antithrombotic therapies are emerging. Herein we investigated thrombogenesis of human arteries with/without atherosclerosis, and the interaction of coagulation and vascular components, we and explored the anti-thrombogenic efficacy of blockade of the P2X purinoceptor 7 (P2X7). A confocal blood flow videomicroscopy system was performed on cryosections of internal mammary artery (IMA) or carotid plaque (CPL) determining/localizing platelets and fibrin. Blood from healthy donors elicited thrombi over arterial layers. Confocal microscopy associated thrombus with tissue presence of collagen type I, laminin, fibrin(ogen) and tissue factor (TF). The addition of antibodies blocking TF (aTF) or factor XI (aFXI) to blood significantly reduced fibrin deposition, variable platelet aggregation and aTF + aFXI almost abolished thrombus formation, showing synergy between coagulation pathways. A scarce effect of aTF over sub-endothelial regions, more abundant in tissue TF and bundles of laminin and collagen type I than deep intima, may suggest tissue thrombogenicity as molecular structure-related. Consistently with TF-related vascular function and expression of P2X7, the sections from CPL but not IMA tissue cultures pre-treated with the P2X7 antagonist A740003 demonstrated poor thrombogenesis in flow experiments. These data hint to local targeting studies on P2X7 modulation for atherothrombosis prevention/therapy.

Hypoxic Conditions Promote Rhythmic Contractile Oscillations Mediated by Voltage-Gated Sodium Channels Activation in Human Arteries

Arterial smooth muscle exhibits rhythmic oscillatory contractions called vasomotion and believed to be a protective mechanism against tissue hypoperfusion or hypoxia. Oscillations of vascular tone depend on voltage and follow oscillations of the membrane potential. Voltage-gated sodium channels (Nav), responsible for the initiation and propagation of action potentials in excitable cells, have also been evidenced both in animal and human vascular smooth muscle cells (SMCs). For example, they contribute to arterial contraction in rats, but their physiopathological relevance has not been established in human vessels. In the present study, we investigated the functional role of Nav in the human artery. Experiments were performed on human uterine arteries obtained after hysterectomy and on SMCs dissociated from these arteries. In SMCs, we recorded a tetrodotoxin (TTX)-sensitive and fast inactivating voltage-dependent INa current. Various Nav genes, encoding -subunit isoforms sensitive (Nav 1.2; 1.3; 1.7) and resistant (Nav 1.5) to TTX, were detected both in arterial tissue and in SMCs. Nav channels immunostaining showed uniform distribution in SMCs and endothelial cells. On arterial tissue, we recorded variations of isometric tension, ex vivo, in response to various agonists and antagonists. In arterial rings placed under hypoxic conditions, the depolarizing agent KCl and veratridine, a specific Nav channels agonist, both induced a sustained contraction overlaid with rhythmic oscillations of tension. After suppression of sympathetic control either by blocking the release of catecholamine or by antagonizing the target adrenergic response, rhythmic activity persisted while the sustained contraction was abolished. This rhythmic activity of the arteries was suppressed by TTX but, in contrast, only attenuated by antagonists of calcium channels, Na+/Ca2+ exchanger, Na+/K+-ATPase and the cardiac Nav channel. These results highlight the role of Nav as a novel key element in the vasomotion of human arteries. Hypoxia promotes activation of Nav channels involved in the initiation of rhythmic oscillatory contractile activity.

An Optimized Method for 3D Magnetic Navigation of Nanoparticles inside Human Arteries

A computational method for optimum magnetic navigation of nanoparticles that are coated with anticancer drug inside the human vascular system is presented in this study. For this reason a 3D carotid model is employed. The present model use Computational Fluid Dynamics (CFD) and Discrete Element Method (DEM) techniques along with Covariance Matrix Adaptation (CMA) evolution strategy for the evaluation of the optimal values of the gradient magnetic field. Under the influence of the blood flow the model evaluates the effect of different values of the gradient magnetic field in order to minimize the distance of particles from a pre-described desired trajectory. Results indicate that the diameter of particles is a crucial parameter for an effective magnetic navigation. The present numerical model can navigate nanoparticles with diameter above 500 nm with an efficiency of approximately 99%. It is found that the velocity of the blood seems to play insignificant role in the navigation process. A reduction of 25% in the inlet velocity leads the particles only 3% closer to the desired trajectory. Finally, the computational method is more efficient as the diameter of the vascular system is minimized because of the weak convective flow. Under a reduction of 50% in the diameter of the carotid artery the computational method navigate the particles approximately 75% closer to the desired trajectory. The present numerical model can be used as a tool for the determination of the parameters that mostly affect the magnetic navigation method.

Aggregated LDL turn human macrophages into foam cells and induce mitochondrial dysfunction without triggering oxidative or endoplasmic reticulum stress

Uptake of modified lipoproteins by macrophages turns them into foam cells, the hallmark of the atherosclerotic plaque. The initiation and progression of atherosclerosis have been associated with mitochondrial dysfunction. It is known that aggregated low-density lipoproteins (agLDL) induce massive cholesterol accumulation in macrophages in contrast with native LDL (nLDL) and oxidized LDL (oxLDL). In the present study we aimed to assess the effect of agLDL on the mitochondria and ER function in macrophage-derived foam cells, in an attempt to estimate the potential of these cells, known constituents of early fatty streaks, to generate atheroma in the absence of oxidative stress. Results show that agLDL induce excessive accumulation of free (FC) and esterified cholesterol in THP-1 macrophages and determine mitochondrial dysfunction expressed as decreased mitochondrial membrane potential and diminished intracellular ATP levels, without generating mitochondrial reactive oxygen species (ROS) production. AgLDL did not stimulate intracellular ROS (superoxide anion or hydrogen peroxide) production, and did not trigger endoplasmic reticulum stress (ERS) or apoptosis. In contrast to agLDL, oxLDL did not modify FC levels, but stimulated the accumulation of 7-ketocholesterol in the cells, generating oxidative stress which is associated with an increased mitochondrial dysfunction, ERS and apoptosis. Taken together, our results reveal that agLDL induce foam cells formation and mild mitochondrial dysfunction in human macrophages without triggering oxidative or ERS. These data could partially explain the early formation of fatty streaks in the intima of human arteries by interaction of monocyte-derived macrophages with non-oxidatively aggregated LDL generating foam cells, which cannot evolve into atherosclerotic plaques in the absence of the oxidative stress.