Simple model of atherosclerosis in cylindrical arteries: impact of anisotropic growth on Glagov remodeling.

In 1987, Seymour Glagov observed that arteries went through a two-stage remodeling process as a result of plaque growth: first, a compensatory phase where the lumen area remains approximately constant and second, an encroachment phase where the lumen area decreases over time. In this paper, we investigate the effect of growth anisotropy on Glagov remodeling in five different cases: pure radial, pure circumferential, pure axial, isotropic and general anisotropic growth where the elements of the growth tensor are chosen to minimize the total energy. We suggest that the nature of anisotropy is inclined towards the growth direction that requires the least amount of energy. Our framework is the theory of morphoelasticity on an axisymmetric arterial domain. For each case, we explore their specific effect on the Glagov curves. For the latter two cases, we also provide the changes in collagen fiber orientation and length in the intima, media and adventitia. In addition, we compare the total energy produced by growth in radial, circumferential and axial direction and deduce that using a radially dominant anisotropic growth leads to lower strain energy than isotropic growth.

Tunica intima compensation for reduced stiffness of the tunica media in aging renal arteries as measured with scanning acoustic microscopy.

OBJECTIVES: Aging causes stiffness and decreased function of the renal artery (RA). Histological study with light microscopy can reveal microscopic structural remodeling but no functional changes. The present study aimed to clarify the association between structural and functional aging of the RA through the use of scanning acoustic microscopy. METHODS: Formalin-fixed, paraffin-embedded cross-sections of renal arteries from 64 autopsy cases were examined. Speed-of-sound (SOS) values of three layers, which correspond to the stiffness, were compared among different age groups. SOS of the tunica media was examined in terms of blood pressure (BP) and SOS of the ascending aorta. Vulnerability to proteases was assessed by SOS reduction after collagenase treatment. RESULTS: The tunica intima presented inward hypertrophy with luminal narrowing, and the tunica media showed outward hypertrophic remodeling with aging. SOS of the tunica media and internal and external elastic laminae showed a reverse correlation with age. SOS of the tunica media was negatively correlated with BP and strongly associated with that of the aorta. The tunica media of young RAs were more sensitive to collagenase compared with the old ones. CONCLUSIONS: Scanning acoustic microscopy is useful for observing the aging process of the RA. This technique simultaneously shows structural and mechanical information from each portion of the RA. In the process of aging, the RA loses contractile function and elasticity as a result of protease digestion. The tunica media and the internal and external elastic laminae exhibit reduced stiffness, but the tunica intima stiffens with atherosclerosis. As a consequence, the RA's outer shape changes from round to oval with inward and outward hypertrophy. This indicates that the inner resistant intima supports the mechanical weakness of the tunica media to compensate for an increase in BP with aging.

Chronic inflammation within the vascular wall in pulmonary arterial hypertension: more than a spectator.

This review seeks to provide an update of preclinical findings and available clinical data on the chronic persistent inflammation and its direct role on the pulmonary arterial hypertension (PAH) progression. We reviewed the different mechanisms by which the inflammatory and immune pathways contribute to the structural and functional changes occurring in the three vascular compartments: the tunica intima, tunica media, and tunica adventitia. We also discussed how these inflammatory mediator changes may serve as a biomarker of the PAH progression and summarize unanswered questions and opportunities for future studies in this area.

Relationship of a thinned medial layer to the attenuated contractile response in atherosclerotic coronary arteries.

Coronary arteries with advanced atherosclerosis do not necessarily have greater contractile responses than those with early atherosclerosis. This study aimed to clarify the relationship between thickness of the medial layer and the contractile response to acetylcholine (ACh) in coronary artery using optical coherence tomography (OCT). The OCT and the vasomotor response to ACh in the left anterior descending coronary artery were assessed in 32 patients with previous myocardial infarction. The intimal and medial layer areas were measured by planimetric analysis of the OCT images. The coronary contractile response to ACh had a positive linear relationship with medial area (r = 0.61, P < 0.001). In contrast, the relationship between the coronary contractile response to ACh and intimal area was described by an inverted U-shaped curve that was fitted to a quadratic regression model (R2 = 0.35, P = 0.002, y-axis, contraction; x-axis, intimal area). The contractile response increased as the intimal layer thickened up to the inflection point; thereafter, the contractile response declined. The relationship between medial area and intimal area was also described by an inverted U-shaped curve that was fitted to a quadratic regression model (R2 = 0.41, P < 0.01, y-axis, medial area; x-axis, intimal area). The medial area increased as the intimal area thickened up to the inflection point; thereafter, the medial area thinned. In conclusion, the thinned medial layer was associated with the attenuated contractile response in a coronary artery with greater atherosclerosis.NEW & NOTEWORTHY This is the first clinical study to show the relationship between the contractile response and the thickness of medial smooth muscle layer in coronary artery of patients with previous myocardial infarction using OCT. The contractile response to acetylcholine was attenuated, and medial layer area was thinned in coronary artery with greater atherosclerosis compared with those in coronary artery with mild or moderate atherosclerosis. The coronary contractile response was positively correlated with thickness of the medial layer in coronary arteries with either mild or greater atherosclerosis. Thus, coronary arteries with advanced atherosclerosis do not necessarily have greater contractile responses than those with early atherosclerosis, which could be related to the thinned medial layer.

Venous intima-media thickness increases both in deep and superficial systems in patients with great saphenous vein reflux.

OBJECTIVE: To evaluate by Doppler ultrasound (DUS) the venous intima-media thickness (vIMT) in patients with or without great saphenous vein (GSV) incompetence. METHODS: A prospective vIMT measurement was performed by DUS in an outpatient cohort. Patients were divided in two groups: group A, patients without GSV reflux; and group B, patients with at least one refluxing GSV. Group B was further divided in group B1, patients with monolateral refluxing GSV; and group B2, patients with bilateral GSV reflux. The vIMT was measured in the femoral vein (FV), 3 to 5 cm distal to the saphenofemoral junction (vIMT[FV]), and in the GSV, 3 to 5 cm from saphenofemoral junction (vIMT[R-] or vIMT[R+]) in the case of a nonrefluxing or a refluxing GSV, respectively. Only one limb per patient was considered for vIMT analysis: in group A, the limb with the greater vIMT(R-), in subgroup B1 the limb with a refluxing GSV, and in subgroup B2 the limb with the lower vIMT(R+). The primary outcome was the difference of vIMT of GSV between groups A and B. Secondary outcomes were differences in vIMT(FV) among groups and the correlation between vIMT of GSV and demographic or clinical parameters. A subgroup analysis of vIMT in GSV was conducted in B1 patients, describing vIMT variations in both limbs. RESULTS: Forty-four patients were enrolled. In the group A (26 patients), vIMT of the GSV was lower than in the group B (18 patients; 0.31 ± 0.01 mm vs 0.49 ± 0.02 mm; P < .001). The difference was significant also for vIMT(FV) (group A, 0.67 ± 0.02 mm vs group B, 0.77 ± 0.03 mm; P < .014). No statistical correlation between age, body mass index, family history, or use of elastic stockings and vIMT(FV) or vIMT(R+ or R-) was detected. Considering the whole population, vIMT of GSV was higher in patients with Clinical, Etiology, Anatomy and Pathophysiology (CEAP) class C of 2 or greater than in classes C 0 and 1 (0.43 ± 0.02 mm vs 0.32 ± 0.02 mm; P < .0002). The difference was significant also for vIMT(FV) in patients with class a class C of 2 or greater and C of 0 to 1 (0.77 ± 0.02 mm vs 0.64 ± 0.03 mm; P < .0008, respectively). In group B1, vIMT(R+) was higher than vIMT(R-) (0.50 ± 0.02 mm vs 0.32 ± 0.02 mm, respectively; P < .0001). The difference was not significant for vIMT(FV). CONCLUSIONS: vIMT seems to be an indirect marker of saphenous insufficiency. In GSV incompetence, an augmented wall thickening is visible in the FV as well. Further studies are needed to assess the accuracy of DUS measurements of vIMT. Longitudinal studies are also needed to evaluate possible GSV and FV vIMT variations related to disease progression or treatment.

Segmental Arterial Mediolysis with Preceding Symptoms Resembling Viral Infection Hampers the Differentiation from Polyarteritis Nodosa.

A middle-aged man presented with a fever, arthralgia, gastrointestinal symptoms, headache, and rash. After two weeks, the patient suddenly complained of severe abdominal pain, and computed tomography revealed aneurysms in the hepatic and splenic arteries, which increased in size progressively. Given the elevated levels of inflammatory markers and orchitis, polyarteritis nodosa (PN) was initially suspected. Catheter embolization for the ruptured hepatic aneurysm and splenectomy for the large splenic ones were performed, and the pathological finding was consistent with segmental arterial mediolysis (SAM). Changes in inflammatory marker levels and aneurysmal size are also informative to differentiate SAM from PN.

The Vicious Cycle of Arterial Stiffness and Arterial Media Calcification.

Arterial media calcification and arterial stiffness are independent predictors of cardiovascular mortality. Both processes reinforce one another, creating a vicious cycle in which transdifferentiation of endothelial cells and vascular smooth muscle cells play a central role. Physiological functioning of vascular smooth muscle cells in the arterial medial layer greatly depends on normal endothelial cell behavior. Endothelial or intimal layer cells are the primary sensors of pathological triggers circulating in the blood during, for example, ageing or inflammation, and often can be seen as initiators of this vicious cycle. As such, the search for treatment of arterial media calcification, which until now has been mainly concentrated at the level of the vascular smooth cell, may need to be expanded to intimal layer targets.

Regional distribution of layer-specific circumferential residual deformations and opening angles in the porcine aorta.

Information on the layer-specific residual deformations of aortic tissue and how these vary throughout the vessel is important for understanding the regionally-varying aortic functions and pathophysiology, but not so much can be found in the literature. Toward this end, porcine aortas were sectioned into eighteen rings, with one ring from each anatomical position radially cut to obtain the zero-stress state for the intact wall and the other ring dissected into intimal-medial and adventitial layers; these rings were then radially cut to reach the zero-stress state for the intima-media and adventitia. Peripheral variations in internal/external circumferences, thickness, and opening angle of the intact wall and its layers were measured through image analysis at the no-load and zero-stress states. Intact wall and layer circumferences at both states significantly declined along the aorta, as did intact wall and intimal-medial but not adventitial thickness. Adventitia exhibited the greatest opening angles, approaching 180 deg all over the aorta. The opening angles of the intima-media and intact wall were quite similar, with the highest values in the ascending aorta, the lowest at the diaphragm, and increasing subsequently. Bending-related residual stretches were released by radial cutting that were compressive internally and tensile externally, displaying distinct axial variation for the intima-media and intact wall, and non-significant variation for the adventitia. Evidence is provided for the release upon layer separation of compressive stretches in the intima-media and of tensile stretches in the adventitia, whose values were smallest in the descending thoracic aorta and highest near the iliac artery bifurcation.

Anisotropic fractional viscoelastic constitutive models for human descending thoracic aortas.

The generalized fractional Maxwell model, formulated for hyperelastic material within the framework of the nonlinear viscoelasticity with internal variables, is applied to identify viscoelastic constitutive equations from layer-specific experimental data obtained by uniaxial harmonic loading of ex-vivo human descending thoracic aortas. The constitutive parameters are identified by using a genetic algorithm for the optimal fitting of the experimental data. The accuracy of the fitted fractional model is compared to the fitted integer order model with the same number of Maxwell elements. The formulation of an original strain energy density function for anisotropic nonlinear viscoelasticity is introduced and constitutive parameters are obtained from the experiments.

Mechanical damage characterization in human femoropopliteal arteries of different ages.

Endovascular treatment of Peripheral Arterial Disease (PAD) is notorious for high failure rates, and interaction between the arterial wall and the repair devices plays a significant role. Computational modeling can help improve clinical outcomes of these interventions, but it requires accurate inputs of elastic and damage characteristics of the femoropopliteal artery (FPA) which are currently not available. Fresh human FPAs from n = 104 tissue donors 14-80 years old were tested using planar biaxial extension to capture elastic and damage characteristics. Damage initiation stretches and stresses were determined for both longitudinal and circumferential directions, and their correlations with age and risk factors were assessed. Two and four-fiber-family invariant-based constitutive models augmented with damage functions were used to describe stress softening with accumulating damage. In FPAs younger than 50 years, damage began accumulating after 1.51 ±â€¯0.13 and 1.49 ±â€¯0.11 stretch, or 196 ±â€¯110 kPa and 239 ±â€¯79 kPa Cauchy stress in the longitudinal and circumferential directions, respectively. In FPAs older than 50 years, damage initiation stretches and stresses decreased to 1.27 ±â€¯0.09 (106 ±â€¯52 kPa) and 1.26 ±â€¯0.09 (104 ±â€¯59 kPa), respectively. Damage manifested primarily as tears at the internal and external elastic laminae and within the tunica media layer. Higher body mass index and presence of diabetes were associated with lower damage initiation stretches and higher stresses. The selected constitutive models were able to accurately portray the FPA behavior in both elastic and inelastic domains, and properties were derived for six age groups. Presented data can help improve fidelity of computational models simulating endovascular PAD repairs that involve arterial damage. STATEMENT OF SIGNIFICANCE: This manuscript describes inelastic, i.e. damage, behavior of human femoropopliteal arteries, and provides values for three constitutive models simulating this behavior computationally. Using a set of 104 human FPAs 14-80 years old, we have investigated stress and stretch levels corresponding to damage initiation, and have studied how these damage characteristics change across different age groups. Presented inelastic arterial characteristics are important for computational simulations modeling balloon angioplasty and stenting of peripheral arterial disease lesions.

Nonthrombotic proliferative vasculopathy associated with antiphospholipid antibodies: A case report and literature review.

A 20-year-old man presented with recurrent hemoptysis for seven months. A small subpleural nodule in his right lower lobe was found and excised surgically. Based on the presence of antiphospholipid antibodies (aPL) and vascular wall hypertrophy without vasculitis or an intraluminal thrombus, nonthrombotic proliferative vasculopathy (NTPV) affecting pulmonary arteries was diagnosed. Recently, aPL have been postulated to directly induce the proliferation of vascular cells in the intima and media, leading to NTPV. We review 5 cases of NTPV-associated aPL with critical ischemia in the lower extremities and gastrointestinal infarction. NTPV-associated aPL might be distinct from classic antiphospholipid syndrome and should be considered in aPL-positive patients who present with vascular occlusions of medium-sized vessels in the absence of atherosclerotic risk factors and systemic or local inflammation.

Media sclerosis drives and localizes atherosclerosis in peripheral arteries.

Media sclerosis (MS) and peripheral artery disease (PAD) may coincide, particularly in type 2 diabetics (T2D) and in patients with chronic kidney disease (CKD). In contrast to non-diabetics, in T2D PAD is more severe and more distal. Although MS is suspected to play a role, the underlying pathophysiological reasons for the differences still remain elusive today. We tested the hypothesis that MS is a promoter of atherosclerosis as it occurs in T2D with PAD by interfering with arterial remodeling using an in-silico simulation. We confirmed that MS aggravates PAD by promoting negative remodeling. We found that the effect is more pronounced in smaller distal arteries compared to larger proximal ones. Our results suggest that the degree of this divergence depends on the ratio between the thickness of the intima relative to the thickness of the media/adventitia of the individually affected arteries.

Modeling mechano-driven and immuno-mediated aortic maladaptation in hypertension.

Uncontrolled hypertension is a primary risk factor for diverse cardiovascular diseases and thus remains responsible for significant morbidity and mortality. Hypertension leads to marked changes in the composition, structure, properties, and function of central arteries; hence, there has long been interest in quantifying the associated wall mechanics. Indeed, over the past 20 years there has been increasing interest in formulating mathematical models of the evolving geometry and biomechanical behavior of central arteries that occur during hypertension. In this paper, we introduce a new mathematical model of growth (changes in mass) and remodeling (changes in microstructure) of the aortic wall for an animal model of induced hypertension that exhibits both mechano-driven and immuno-mediated matrix turnover. In particular, we present a bilayered model of the aortic wall to account for differences in medial versus adventitial growth and remodeling and we include mechanical stress and inflammatory cell density as determinants of matrix turnover. Using this approach, we can capture results from a recent report of adventitial fibrosis that resulted in marked aortic maladaptation in hypertension. We submit that this model can also be used to identify novel hypotheses to guide future experimentation.

Hypertension Induced Morphological and Physiological Changes in Cells of the Arterial Wall.

Morphological and physiological changes in the vasculature have been described in the evolution and maintenance of hypertension. Hypertension-induced vascular dysfunction may present itself as a contributing, or consequential factor, to vascular remodeling caused by chronically elevated systemic arterial blood pressure. Changes in all vessel layers, from the endothelium to the perivascular adipose tissue (PVAT), have been described. This mini-review focuses on the current knowledge of the structure and function of the vessel layers, specifically muscular arteries: intima, media, adventitia, PVAT, and the cell types harbored within each vessel layer. The contributions of each cell type to vessel homeostasis and pathophysiological development of hypertension will be highlighted.

Arterial Wall Characteristics in Patients With Peripheral Arterial Disease. Preliminary Data Obtained at Different Arterial Sites by Radiofrequency-Based Wall Tracking System.

The common carotid artery (CCA) and the common femoral artery (CFA) have different characteristics. We compared CCA and CFA intima-media thickness (IMT), diameter and stiffness in 50 healthy controls, 50 patients with cardiovascular risk factors (CV-RFs), and 50 patients with peripheral artery diseases (PADs) using radiofrequency-based ultrasound (Rf-US). Common femoral artery-IMT was significantly and similarly increased in patients with both CV-RF and PAD, whereas CCA-IMT was significantly greater only in patients with PAD. Common carotid artery diameter was increased and CFA diameter was decreased in patients with PAD. Common carotid artery and CFA pulse wave velocity (PWV) was increased only in patients with PAD. In the study population, age was directly related to CCA-IMT, diameter, and PWV ( r = .52, .31, and .38; P < .0001 for all) but not to CFA vascular parameters ( P = .10, .62, and .67). Common femoral artery-PWV was inversely related to the ankle-brachial index ( r = -.30; P < .0001). Common femoral artery parameters are less linked to aging than the CCA parameters and may provide additional information on the atherosclerotic process. The Rf-US may be a useful tool for the more complex evaluation of arteries and assessing the impact of age and RFs on arteries.

[Effekt of blood flow shutdown on the vein damage when exposed to HIFU].

The purpose. In the study we investigated the impact of the partial blood flow shutdown on structural changes in the rabbit vena cava posterior wall after exposure to high-intensity focused ultrasound (HIFU). Methods. Ultrasound Exposure: frequency of 1.65 MHz, the ultrasound intensity in the focus of 13.6 kW/cm2, the area of the focal spot 1 mm2, continuous ultrasound, exposure for 3 seconds. Results. Immediately after HIFU exposure all layers of the vein wall showed characteristic signs of thermal damage. A week after exposure structural changes in the intima, media and adventitia was minimal in the part of vessel with preserved blood flow, and after 4 weeks the changes were not revealed. A week after HIFU exposure partial endothelium destruction, destruction of myocytes, disorganization and consolidation of collagen fibers of the adventitia were observed in an isolated segment of the vessel, and in 4 weeks endothelium restored and signs of damage in media and adventitia persisted, but were less obvious than in a week after exposure. Conclusion. The shutdown of blood flow after exposure to HIFU promotes persistent changes in the vein wall. Vein compression appears to be necessary for the obliteration of the vessel, when using HIFU-technology.

Vascular Calcification: Current Genetics Underlying This Complex Phenomenon.

OBJECTIVE: Vascular calcification is the consequence of the complex interaction between genetic, environmental, and vascular factors, which ultimately lead to the deposition of calcium in the tunica intima (atherosclerotic calcification) or tunica media (Mönckenberg's sclerosis). Vascular calcification is also closely related to other pathologies, such as diabetes mellitus, dyslipidemia, and chronic kidney disease. It has been concluded that the degree of vascular calcification may vary from person to person, even if the associated pathologies and environmental factors are the same. Therefore, this suggests an important genetic contribution to the development of vascular calcification. This review aimed to find the most recent evidence about vascular calcification pathophysiology regarding the genetic aspects and molecular pathways. DATA SOURCES: We conducted an exhaustive search in Scopus, EBSCO, and PubMed with the keywords "genetics and vascular calcification", "molecular pathways, genetic and vascular calcification" and included the main articles from January 1995 up to August 2016. We focused on the most recent evidence about vascular calcification pathophysiology regarding the genetic aspects and molecular pathways. STUDY SELECTION: The most valuable published original and review articles related to our objective were selected. RESULTS: Vascular calcification is a multifactorial disease; thus, its pathophysiology cannot be explained by a single specific factor, rather than by the result of the association of several genetic variants, molecular pathway interactions, and environmental factors that promote its development. CONCLUSION: Although several molecular aspects of this mechanism have been elucidated, there is still a need for a better understanding of the factors that predispose to this disease.

Longitudinal Motion Assessment of the Carotid Artery Using Speckle Tracking and Scale-Invariant Feature Transform.

The purpose of this work is to present and validate a novel approach for ultra-sound-based speckle tracking to measure the carotid artery longitudinal displacement, and to assess the apparent sliding between of Intima-Media Complex (IMC) and Adventitia (Ad) layers. This method utilizes feature detectors and descriptors to localize and track keypoints for local motion quantification. The procedure was tested and validated on an in silico dataset and on 18 heathy volunteers and 16 patients. Accuracy measured on in silico data gave a mean ± standard deviation of 23 ± 15 and 19 ± 18 µm for IMC and Ad respectively, and thus smaller than the pixel size (0.0925 mm). Robustness analysis was performed on in vivo images, obtaining a maximum variation coefficient, over 5 repeated measures, of 9.5 and 13.8% for IMC and Ad, respectively. The novel method capability for detecting the relative motion of IMC vs. Ad was compared with visual assessment performed by 2 physicians, leading to a correlation coefficient R of 0.7 in the worst case. (Healthy group scored by rater #1.) In conclusion, our results provide evidence that the novel method is able to accurately and reliably track carotid artery layer motion and that it overcomes limitations currently present in the literature, therefore providing an automatic tool for clinical evaluation of IMC vs. Ad relative displacement.

[Stiffness of the arterial wall and predicted vascular age as a predictor of cardiovascular disease when stress-induced hypertension in the military personnel].

Stiffness of the arterial wall and predicted vascular age as a predictor of cardiovascular disease when stress-induced hypertension in the military personnel. On the basis of the study of 156 men aged 30-55 years are considered diagnostic methods for stress-induced hypertension in the military personnel. Furthermore, using modern diagnostic methods determined stress effect on the development of stress-induced hypertension, and also the risk of cardiovascular diseases. In order to detect early signs of atherosclerosis used sphygmography, by means of which was determined by cardio ankle vascular index (CA VI), as well as the calculated vascular age. The study proposed a set of organizational, diagnostic and therapeutic measures to reduce the risk of cardiovascular diseases among military personnel exposed to occupational stressful load.

Analysis of arterial wall remodeling in hypertension based on lamellar modeling.

Arterial wall remodels its geometry and mechanical properties in response to hypertension to maintain functionality. The elevated pressure is sensed through cellular mechanotransduction pathways, and extra extracellular matrix is synthesized, leading to thickening and stiffening. The present study enquires the response of aortic lamellar structure to hypertensive blood pressure regarding unchanged circumferential stress "profile" across the media as remodeling criterion. We tested the hypothesis that alterations in the thickness of structural layers contributes to maintain stress profile with least deviation from normotensive conditions. To test this notion, finite element analysis was recruited to evaluate stress profile, considering wall residual stress, and lamellar structure was adjusted through an optimization algorithm. Our results indicated 47% increased thickness of the aortic media that originates from nonhomogenous thickening of the microstructural units. The thickening and stiffening responses of the wall tissue were coupled, and the optimized pattern of hypertension-induced remodeling was established.