Healthy Arteries Research Articles

A fluid–structure interaction study to analyze the severity of carotid artery stenosis at different locations and its effect on various hemodynamic biomarkers

The study on arterial stenosis has gained rapid interest among researchers in the last decade because of its chronic consequences. Several researchers have tried to investigate stenosis and plaque progression in the carotid artery with different simulation models. In this study, a realistic 3-D geometry of the carotid artery has been used to analyze the effect of varying degrees of stenosis present at different locations of the carotid artery on various hemodynamic parameters. An extensive range of stenosis degrees, starting from a healthy artery(0 %stenosis) to 10%, 30%, 50%, 75%, and 90% stenosis, have been studied. These degrees of stenosis were planted at different locations of the artery grown simultaneously. The whole study was done under the realm of Fluid–Structure Interaction multiphysics. The change in velocity profiles at the areas of stenosis has been found along with the wall shear stress and arterial displacement. The magnitude of velocity and wall shear stress in the case of multiple stenosis locations has been found to be dependent on each other. The presence or absence of one stenosis affects the other, and given the regular and irregular patterns of the velocity profile, wall shear stress, and displacement, their inclusion in blood flow simulation studies having multiple stenoses should be considered.

Optimization of pulmonary artery mechanical testing

Pulmonary arterial hypertension (PAH) is an incurable disease with mortality within 3 years in 28-55% of high-risk patients. The progression of PAH has been known to be associated with increased vascular stiffness and vascular remodeling. Recent studies have suggested that increased stiffness may in fact be a driver for some of the metabolic abnormalities observed during PAH. To gain more insights into this relationship, we need to quantify the differences in mechanical properties of healthy and hypertensive pulmonary arteries. The stress-strain relationship is the gold standard for the ex-vivo stiffness measurement of arteries. This is obtained by obtaining force vs. distension data by tensile testing and using sample dimensions, i.e. length, lumen diameter, and wall thickness, to calculate engineering stress and strain. While this approach is well-optimized for large muscular arteries, it has not been used to test pulmonary arteries as their thin walls and low basal tone make it challenging to make precise measurements of sample wall thickness and lumen diameter. Thus, the goals of this study were to: 1) establish a reliable protocol for rat pulmonary artery tensile testing and 2) quantify the differences in stiffness between hypertensive and healthy pulmonary arteries. First, a methodology to improve the fidelity of determining the lumen diameter and wall thickness was developed. Using this approach, we observed that the modulus was negatively correlated with the length of the vessel segment tested. This suggests that vessel length should be standardized to perform reliable comparisons between groups. Next, we performed tensile tensing on both control and hypertensive pulmonary arteries, after standardizing vessel segment lengths. We initially modeled this tensile testing data using a one-term exponential equation and we observed that intact hypertensive arteries were ~2.7 times stiffer than control arteries at low strain (strain = 0.8). Whereas at high strain (strain = 2.8) intact and decellularized hypertensive arteries were 20 and 29 times stiffer than control arteries respectively. To better capture the viscoelastic properties of both, the cellular and ECM components of the vessels we also fit the tensile testing data using a two-term exponential equation. Using this two-term exponential model, we observed that hypertensive vessels were 2.2 times stiffer than the controls at normal hoop stress (20 kPa), and at the hypertensive hoop stress (66 kPa) the diseased vessels showed less variability in stiffness as compared to the controls. These findings and the methods developed in this study will be helpful in conducting and analyzing experiments to investigate the relationship between changes in biomechanical signals and the progression of PAH. R01HL151530 (KS), R01HL126514 (LS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 1054: Toll-like Receptor 4 Is A New Regulator Of Smooth Muscle Cell Phenotypic Transitions

Objectives: There is growing evidence that smooth muscle cell ( SMC ) phenotypic transitions have a critical role in cardiovascular pathologies, including atherosclerosis. However, molecular mechanisms regulating different aspects of these transitions are still not fully elucidated. We previously found that the pluripotency factor OCT4 plays a protective role in SMC in atherogenesis and neointioma formation after vascular injury. Using a bioinformatics approach, we identified Toll-like receptor 4 ( TLR4 ), an integral component of the innate immune system, pivotal in eliciting inflammatory responses, as an indirect target of OCT4 in SMC. However, it is not yet elucidated whether OCT4/TLR4 axis has a role in SMC transitions. Methods and Results: First, we used blocking siRNA against Oct4 and different downstream targets of the TLR4 signaling ( Trif , Irf3 ), as well as a TLR4 inhibitor TAK242 (Resatorvid) in cultured mouse aortic SMC treated with the oxidized phospholipid, POVPC. These experiments demonstrated that blocking TLR4 signaling in wild-type SMC resulted in suppression of SMC contractile genes and up-regulation of LGALS3 (SMC transition marker). In contrast, TAK242 treatment decreased LGALS3 levels in OCT4 deficient SMC, indicating that TLR4, at least in part, is responsible for the SMC phenotype in OCT4 deficient SMC. Next, using the bioinformatics approach and Chromatin Immunoprecipitation assays, we identified the EST Proto-oncogene 1 ( ETS1 ) transcriptional factor as a target of OCT4 that directly regulates TLR4. Interestingly, on the other hand, we found that overexpression of TLR4 led to OCT4 activation in SMC, and, oppositely, the inhibition of TLR4 signaling by TAK242 resulted in significant decreases in the POVPC-induced OCT4 activation, indicating that TLR4 signaling is critical for OCT4 activation in SMC. Using an SMC-lineage tracing mouse model combined with a TLR4-IRES-YFP reporter, we demonstrated that TLR4 is highly expressed in the healthy arteries of young mice but not in the phenotypically modulated SMC within the atherosclerotic plaques. Conclusions: These results suggest a negative feedback loop between TLR4 and OCT4 regulating SMC phenotypic transitions.

Computational Analysis of Blood Flow in Healthy Pulmonary Arteries in Comparison to Repaired Tetralogy of Fallot Results: A Small Cohort Study

Characterization of the physiological hemodynamic environment in normal pulmonary arteries is a key factor in understanding pathological conditions. This study aimed to analyze the morphology and hemodynamics in the healthy adult pulmonary bifurcation in comparison to age-matched repaired Tetralogy of Fallot (rTOF) geometries. The pulmonary trunk of five healthy volunteers was reconstructed from 4D Flow-MRI data and was compared to rTOF results. Subject-specific boundary conditions were assigned in both the inlet and outlets of the models, and flow characteristics were analyzed computationally. The morphological and flow features were consistent among the healthy geometries, highlighting the ability of an averaged geometry derived from this small cohort to capture the main flow characteristics. A slightly higher mean time-averaged wall shear stress (TAWSS) was found in the right pulmonary artery, which was also the branch with a higher mean curvature and local Reynolds number. Compared to rTOF results, the averaged healthy geometry demonstrated more than an 8-fold lower value in TAWSS, with the individual patient-specific healthy volunteers showing further reduced TAWSS than the rTOF patients. These observations could be useful in clinical assessment and decision making based on hemodynamic indices.

209 Transcriptomic Analysis of the Post-mortem Brain in Intracranial Atherosclerosis Implicates Interferon Signaling

INTRODUCTION: Intracranial atherosclerotic stenosis (ICAS) is a common cause of ischemic stroke. Stroke patients manifesting symptomatic ICAS often have poor prognoses, including worsened functional outcome, increased morbidity, and mortality. Despite risk factor management, ICAS exhibits a nonlinear rise in incidence with age, with an increase in unstable lipid-rich plaques. Understanding mechanisms of ICAS is crucial to improve clinical outcomes and reduce stroke incidence. Previous studies have demonstrated that intracranial arteries demonstrate different histopathologic profiles compared to extracranial arteries, likely lowering their risk of atherosclerosis. However, these studies are limited to healthy intracranial arteries. Comprehensive multiomic data examining diseased intracranial arteries are limited. METHODS: We performed bulk transcriptomic analysis in 4 tissues in a post-mortem brain dataset (N=304), with 34 patients with cerebral atherosclerosis confirmed via autopsy, 90 patients with peripheral atherosclerosis, and 180 controls. Cell type deconvolution was conducted to identify differential expression signatures in 7 neuronal and glial subtypes. To examine interferon response further in glial cells, we generated human induced pluripotent stem cell (hiPSC)-derived astrocytes treated with 3 doses of interferon and performed transcriptomic analysis. RESULTS: Cerebral atherosclerosis was significantly (pathway enrichment p<10e-9) associated with interferon signaling compared to peripheral atherosclerosis and controls. Glial cells particularly expressed patterns associated with cerebral atherosclerosis. Astrocytes, oligodendrocytes, excitatory neurons, and endothelial cells were most impacted. In hiPSC-derived astrocytes treated with interferon, we identified upregulation of interferon-inducible genes matching those found in intracranial atherosclerosis in the post-mortem brain, implicating glial reactivity to interferon-related stress. CONCLUSIONS: Our study implicates interferon signaling as critical within the development of cerebral atherosclerosis. Protection of the intracranial arteries from atherosclerosis may occur due to reduced expression of interferon-inducible genes. Targeted treatment of cerebral atherosclerosis should consider interferon-signaling modulators.

Plausible Mechanisms of Causation of Immediate Stroke by Cervical Spine Manipulation: A Narrative Review.

It has been proposed that cervical spine manipulation (CSM) can cause dissection in healthy cervical arteries, with resultant immediate stroke. However, research does not support a causal association between CSM and cervical artery dissection (CAD) in healthy cervical arteries. The objective of this study was to review the literature to identify plausible mechanisms of causation of immediate stroke by CSM. Immediate stroke is defined as a stroke occurring within seconds or minutes of CSM. Our review found plausible thromboembolic and thrombotic mechanisms of causation of immediate stroke by CSM in the literature. The common premise of these mechanisms is CAD being present before CSM, not occurring as a result of CSM. These mechanisms of causation have clinical and medicolegal implications for physicians performing CSM.

Small nucleolar RNA host gene 18 controls vascular smooth muscle cell contractile phenotype and neointimal hyperplasia.

Long non-coding RNA (LncRNA) small nucleolar RNA host gene 18 (SNHG18) has been widely implicated in cancers. However, little is known about its functional involvement in vascular diseases. Herein, we attempted to explore a role for SNHG18 in modulating vascular smooth muscle cell (VSMC) contractile phenotype and injury-induced neointima formation. Analysis of single-cell RNA sequencing and transcriptomic datasets showed decreased levels of SNHG18 in injured and atherosclerotic murine and human arteries, which is positively associated with VSMC contractile genes. SNHG18 was upregulated in VSMCs by TGFβ1 through transcription factors Sp1 and SMAD3. SNHG18 gene gain/loss-of-function studies revealed that VSMC contractile phenotype was positively regulated by SNHG18. Mechanistic studies showed that SNHG18 promotes a contractile VSMC phenotype by up-regulating miR-22-3p. SNHG18 up-regulates miR-22 biogenesis and miR-22-3p production by competitive binding with the A-to-I RNA editing enzyme, adenosine deaminase acting on RNA-2 (ADAR2). Surprisingly, we observed that ADAR2 inhibited miR-22 biogenesis not through increasing A-to-I editing within primary miR-22, but by interfering with the binding of microprocessor complex subunit DGCR8 to primary miR-22. Importantly, perivascular SNHG18 overexpression in the injured vessels dramatically up-regulated the expression levels of miR-22-3p and VSMC contractile genes, and prevented injury-induced neointimal hyperplasia. Such modulatory effects were reverted by miR-22-3p inhibition in the injured arteries. Finally, we observed a similar regulator role for SNHG18 in human VSMCs and a decreased expression level of both SNHG18 and miR-22-3p in diseased human arteries; and we found that the expression level of SNHG18 was positively associated with that of miR-22-3p in both healthy and diseased human arteries. We demonstrate that SNHG18 is a novel regulator in governing VSMC contractile phenotype and preventing injury-induced neointimal hyperplasia. Our findings have important implications for therapeutic targeting snhg18/miR-22-3p signalling in vascular diseases.

Biological differences of three paclitaxel- and sirolimus-coated balloons on coronary lesions in a rabbit model.

Drug-coated balloons (DCBs) are important treatment options for coronary artery disease; however, randomised controlled trials comparing various DCB technologies are sparse, and further investigations are needed. This preclinical study aimed to histologically and biologically compare the drug effects and safety of a low-dose paclitaxel-coated DCB (PCB; AGENT), a regular-dose PCB (SeQuent Please NEO) and a sirolimus-coated DCB (SCB; MagicTouch). The DCBs were inflated in the healthy iliac arteries of 18 rabbits, which were euthanised after 28 days. The treated iliac arteries and distal skeletal muscles were histopathologically evaluated, and drug concentrations were measured. In the histopathological evaluation, the medial smooth muscle cell loss score regarding depth, an indicator of drug efficacy, was significantly higher with AGENT and SeQuent Please NEO than with MagicTouch (4.0 [3.6-4.0] vs 3.7 [3.7-4.0] vs 2.2 [2.0-2.4]), with significant differences in comparisons between AGENT and MagicTouch (p<0.01) and between SeQuent Please NEO and MagicTouch (p<0.01). AGENT and SeQuent Please NEO showed comparable drug concentrations in the treated artery (p=0.61). In contrast, the drug concentrations in distal skeletal muscles were the highest for MagicTouch, followed by SeQuent Please NEO and AGENT (28.07 [13.19-52.46] ng/mg vs 0.66 [0.22-3.76] ng/mg vs 0.25 [0.04-3.23] ng/mg, respectively). This study demonstrated that PCBs might have higher efficacy and lower drug concentrations in distal skeletal muscles than the MagicTouch SCB. The efficacy of the AGENT low-dose PCB and the SeQuent Please NEO regular-dose PCB was comparable.

Cascaded Plane Wave Ultrasound for Blood Velocity Vector Imaging in the Carotid Artery.

Cascaded dual-polarity waves (CDWs) imaging increases the signal-to-noise ratio (SNR) by transmitting trains of pulses with different polarity order, which are combined via decoding afterward. This potentially enables velocity vector imaging (VVI) in more challenging SNR conditions. However, the motion of blood in between the trains will influence the decoding process. In this work, the use of CDW for blood VVI is evaluated for the first time. Dual-angle, plane wave (PW) ultrasound, CDW-coded, and noncoded conventional PW (cPW), was acquired using a 7.8 MHz linear array at a pulse repetition frequency (PRF) of 8 kHz. CDW-channel data were decoded prior to beamforming and cross correlation-based compound speckle tracking for VVI. Simulations of single scatterer motion show a high dependence of amplitude gain on the velocity magnitude and direction for CDW-coded transmissions. Both simulations and experiments of parabolic flow show increased SNRs for CDW imaging. As a result, CDW outperforms cPW VVI in low SNR conditions, based on both bias and standard deviation (SD). Quantitative linear regression and qualitative analyses of simulated realistic carotid artery blood flow show a similar performance of CDW and cPW for high SNR (14 dB) conditions. However, reducing the SNR to 6 dB, results in a root-mean-squared error 2.7× larger for cPW versus CDW, and an R2 of 0.4 versus 0.9. Initial in vivo evaluation of a healthy carotid artery shows increased SNR and more reliable velocity estimates for CDW versus cPW. In conclusion, this work demonstrates that CDW imaging facilitates improved VVI of deeper located carotid arteries.

Assessment of the nano-mechanical properties of healthy and atherosclerotic coronary arteries by atomic force microscopy.

Nano-indentation techniques might be better equipped to assess the heterogeneous material properties of plaques than macroscopic methods but there are no bespoke protocols for this kind of material testing for coronary arteries. Therefore, we developed a measurement protocol to extract mechanical properties from healthy and atherosclerotic coronary artery tissue sections. Young's modulus was derived from force-indentation data. Metrics of collagen fibre density were extracted from the same tissue, and the local material properties were co-registered to the local collagen microstructure with a robust framework. The locations of the indentation were retrospectively classified by histological category (healthy, plaque, lipid-rich, fibrous cap) according to Picrosirius Red stain and adjacent Hematoxylin & Eosin and Oil-Red-O stains. Plaque tissue was softer (p < 0.001) than the healthy coronary wall. Areas rich in collagen within the plaque (fibrous cap) were significantly (p < 0.001) stiffer than areas poor in collagen/lipid-rich, but less than half as stiff as the healthy coronary media. Young's moduli correlated (Pearson's ρ = 0.53, p < 0.05) with collagen content. Atomic force microscopy (AFM) is capable of detecting tissue stiffness changes related to collagen density in healthy and diseased cardiovascular tissue. Mechanical characterization of atherosclerotic plaques with nano-indentation techniques could refine constitutive models for computational modelling.

Spatial lipidomics of coronary atherosclerotic plaque development in a familial hypercholesterolemia swine model

Coronary atherosclerosis is caused by plaque build-up, with lipids playing a pivotal role in its progression. However, lipid composition and distribution within coronary atherosclerosis remain unknown. This study aims to characterize lipids and investigate differences in lipid composition across disease stages to aid in the understanding of disease progression. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to visualize lipid distributions in coronary artery sections (n = 17) from hypercholesterolemic swine. We performed histology on consecutive sections to classify the artery segments and to investigate colocalization between lipids and histological regions of interest in advanced plaque, including necrotic core and inflammatory cells. Segments were classified as healthy (n = 6), mild (n = 6), and advanced disease (n = 5) artery segments. Multivariate data analysis was employed to find differences in lipid composition between the segment types, and the lipids' spatial distribution was investigated using non-negative matrix factorization (NMF). Through this process, MALDI-MSI detected 473 lipid-related features. NMF clustering described three components in positive ionization mode: triacylglycerides (TAG), phosphatidylcholines (PC), and cholesterol species. In negative ionization mode, two components were identified: one driven by phosphatidylinositol(PI)(38:4), and one driven by ceramide-phosphoethanolamine(36:1). Multivariate data analysis showed the association between advanced disease and specific lipid signatures like PC(O-40:5) and cholesterylester(CE)(18:2). Ether-linked phospholipids and LysoPC species were found to colocalize with necrotic core, and mostly CE, ceramide, and PI species colocalized with inflammatory cells. This study, therefore, uncovers distinct lipid signatures correlated with plaque development and their colocalization with necrotic core and inflammatory cells, enhancing our understanding of coronary atherosclerosis progression.

Optimization of resting tension for wire myography in male rat pulmonary arteries.

Wire myography to test vasomotor functions of blood vessels ex-vivo are well-established for the systemic circulation, however, there is no consensus on protocols for pulmonary arteries. We created a standardized wire myography protocol for healthy rat PAs and validated this in a pulmonary hypertension (PH) model. Vessels stretched to higher initial tensions (5.0, 7.5 and 10.0 mN) exhibited a uniform response to phenylephrine, a larger dynamic range, and lower EC50 values. The endothelium-mediated relaxation showed that moderate tensions (7.5 and 10.0 mN) produced robust responses with higher maximum relaxation and lower EC50 values. For endothelium independent responses, the higher initial tension groups had lower and more consistent EC50 values than the lower initial tension groups. Pulmonary arteries from rats with PH were more responsive to vasoactive drugs when subjected to a higher initial tension. Notably, vessels in the PH group subjected to 15.0 mN exhibited high dynamic ranges in contractile and relaxation responses without tearing. Lastly, we observed attenuated cholinergic responses in these vessels-consistent with endothelial dysfunction in PH. Therefore, a moderate initial tension of 7.5-10.0 mN is optimal for healthy rat pulmonary arteries and a higher initial tension of 15.0 mN is optimal for pulmonary arteries from animals with PH.

Effects of hematocrit levels on flow structures and stress levels in the healthy and diseased carotid arteries

Flow structures and wall shear stress (WSS) distribution in human arteries depend strongly on blood rheology. Blood viscosity undergoes significant alterations due to varying hematocrit (Hct) levels. Hematocrit levels can change from the normal level (45%) due to numerous disorders such as leukemia, lymphoma, and congenital heart disease. However, the effects of Hct levels on the flow features and WSS levels in large stenotic arteries are not well reported in literature. The present study computationally assesses the variation in flow features in healthy and stenosed carotid arteries due to changes in blood Hct levels. We have reported variations in axial and secondary flow characteristics, vortex structures, and WSS-based parameters for different Hct levels. Specifically, we consider high (65%) and low (25%) Hct levels in addition to a normal Hct level. Our results reveal that both high and low Hct levels have adverse effects on the hemodynamic features inside a healthy carotid artery model. The low Hct level displays a much more widespread low time-averaged WSS (TAWSS) area, while the high Hct shows an increased oscillatory shear index (OSI) zone at the carotid sinus wall. In stenotic arteries, low Hct enhances the spread of the low TAWSS zone in the post-stenotic carotid sinus, whereas high Hct increases the risk of plaque rupture. The high Hct level also increases the spread of high OSI zone at the inner wall of internal carotid artery for the moderately stenosed artery.

Delineating the effects of morphological changes on retinal hemodynamics in diabetic human retinas: An invitro investigation

Diabetes-related vascular abnormalities are commonly encountered in the retinal vasculature, the most common being the increased tortuosity and reduced lumen diameter. These morphological changes significantly affect the underlying hemodynamics and remain unexplored. The current study examines the changes produced by the altered morphology on the blood flow velocity and wall shear stress (WSS) using particle streak velocimetry (PSV) experiments and numerical simulations and compares it with the healthy scenario. The diabetic and healthy retinal arteries are extracted from patient-specific fundus images and transparently printed using stereolithography (SLA) in three dimensions. Flow visualization experiments are performed using the blood-mimicking fluid (BMF) with three different flow rates, whose values are evaluated using the similarity analysis. Experimental and simulation results illustrate a significant reduction in the average axial velocity and WSS due to tortuosity with maximum percentage reductions of 10% and 11%, respectively, compared to healthy. Additionally, a strong correlation is observed between a particular artery's local tortuosity and the WSS, with a higher tortuosity index leading to the development of low-shear regions inside the diabetic artery. A 14% diameter reduction in the diabetic arteries leads to approximately 65% and 63% increase in the velocity and WSS, respectively, compared to healthy. Moreover, the experiments also capture the effect of decreased blood viscosity on the WSS in the case of diabetic arteries, illustrating a significant decrease in WSS values. The experiments performed in the current study may help ophthalmologists estimate the induced damage that the arterial morphological changes may create and facilitate an accurate prognosis of retinal vascular diseases.

Blood shear stress during the cardiac cycle and endothelial cell orientation and polarity in the carotid artery of male and female mice.

Introduction: Blood flow produces fluid shear stress (SS), a frictional force parallel to the blood flow, on the endothelial cell (EC) layer of the lumen of the vessels. ECs themselves are sensitive to this frictional force in terms of directionality and intensity. The aim of this study was to determine the physiological shear stress value during the cardiac cycle and EC polarity and orientation from blood flow in healthy male and female mouse carotid artery. Methods: Experimentation is done on anesthetized male and female 8-week-old C5BL/6J mice. In vivo measurements of maximum blood velocity and vessel diameter in diastole and systole were performed on the right common carotid artery by Doppler ultrasound imaging. Blood viscosity (total and plasmatic) and hematocrit were determined on blood samples. For SS calculation, we developed a new method assuming heterogenous blood flow, i.e., a red cell central plug flow surrounded by a peripheral plasma sheath flow, and computing SS from vessel diameter and hemodynamical measurements (maximal blood velocity, hematocrit and plasmatic viscosity). Results: Results were compared with the classical method assuming a homogenous blood flow with constant apparent total blood viscosity. EC polarity and orientation were determined ex vivo on the carotid endothelium by confocal imaging after labeling of the EC nucleus and Golgi apparatus. Diastolic and systolic SS were 6 ± 2.5 Pa and 30 ± 6.5 Pa, respectively. Total blood and plasmatic viscosity was 4 ± 0.5 cP and 1.27 cP, respectively. ECs were polarized and significantly oriented against blood flow. No sex difference was identified.

Giant right coronary artery aneurysm: the saphenous vein bridge technique

A giant coronary artery aneurysm is defined as an irreversible dilation that is 1.5-times more than the diameter of a healthy adjacent coronary artery. It is a rare disease with an incidence of 0.2% to 4.9%. Coronary artery aneurysms are usually corrected with a coronary artery bypass graft. We describe how to perform a saphenous vein bridge to repair a giant coronary artery aneurysm. When applicable, this technique allows sparing of the coronary artery ostia and restores the coronary anatomy.

Vascular reactivity is altered in the placentas of fetuses with congenital diaphragmatic hernia

IntroductionInfants with congenital diaphragmatic hernia (CDH) often develop pulmonary hypertension but frequently fail to respond to vasodilator therapy, for instance because of an altered pulmonary vasoreactivity. Investigating such alterations in vivo is impossible. We hypothesised that these alterations are also present in fetoplacental vessels, since both vasculatures are exposed to the same circulating factors (e.g. endothelin-1) and respond similarly to certain stimuli (e.g. hypoxia). As proof-of-concept, we compared fetoplacental vasoreactivity between healthy and CDH-affected placentas. MethodsFetoplacental vascular function of healthy and antenatally diagnosed left-sided CDH fetuses was assessed by wire myography. Placental expression of enzymes and receptors involved in the altered vasoreactive pathways was measured using quantitative PCR. ResultsCDH arteries (n = 6) constricted more strongly to thromboxane A2 agonist U46619 (p < 0.001) and dilated less to bradykinin (p = 0.01) and nitric oxide (NO)-donor sodium nitroprusside (p = 0.04) than healthy arteries (n = 8). Vasodilation to prostacyclin analogue iloprost and adenylate cyclase stimulator forskolin, and vasoconstriction to endothelin-1 were not different between both groups. Angiotensin II did not induce vasoconstriction. Phosphodiesterase inhibitors sildenafil and milrinone did not affect responses to sodium nitroprusside, forskolin, or U46619. The mRNA expression of guanylate cyclase 1 soluble subunit alpha 1 (p = 0.003) and protein kinase cyclic guanine monophosphate (cGMP)-dependent 1 (p = 0.02) were reduced in CDH versus healthy placentas. DiscussionThe identified changes in the thromboxane and NO-cGMP pathways in the fetoplacental vasculature correspond with currently described alterations in the pulmonary vasculature in CDH. Therefore, fetoplacental arteries may provide an opportunity to predict pulmonary therapeutic responses in infants with CDH.

Impact on hemodynamics in carotid arteries with carotid webs at different locations: A Numerical Study Integrating Thrombus Growth Model

ObjectiveCarotid webs (CWs), lesions in the carotid arteries, are gaining research interest due to the unclear link to ischemic stroke. Similarity to atherosclerosis in lesion location adds the complexity. The main purpose of study is to investigate the hemodynamic effects of CWs at different locations in carotid arteries. MethodsThree types of models with CWs were reconstructed from the CTA dataset of 8 healthy carotid arteries (Models A: CWs at the common carotid artery; B: at the origin of internal carotid artery; C: at the carotid sinus). Wall shear stress (WSS)-based parameters, including time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and endothelial cell activation potential (ECAP) were analyzed. A thrombus growth model was also incorporated to assess long-term thrombus formation across different carotid webs locations. ResultsModels A exhibited helical flow, whereas models B and C showed disturbed flow in the carotid sinus. Recirculation in Models A and B was mainly downstream of CWs, while Models C had both upstream and downstream recirculation. In addition, models A had higher overall TAWSS levels, with the smallest region of TAWSS < 0.4 pa (7.78 ± 8.35%). In contrast, Models C had larger areas with TAWSS < 0.4 pa, RRT > 100, and ECAP > 1.5, accounting for 14.18 ± 5.28%, 1.51 ± 1.17%, and 10.36 ± 4.10%, respectively. Noting that thrombus volume was highest in Models C (7.20 ± 3.95%). ConclusionsNumerical simulations indicate that: 1) CWs have less hemodynamic impact when located in the CCA, but may increase flow resistance leading to distal branch ischemia; 2) CWs contribute to thrombus formation, primarily downstream in the common carotid artery and internal carotid artery origin, and both upstream and downstream in the sinus; 3) CWs at the origin of the ICA are more likely to result in disturbed blood flow patterns and thrombus aggregation than the other two locations, which may increase the risk of ischemic stroke in distal cerebral arteries.

In vivo evaluation of intravascular lithotripsy in a healthy porcine coronary model

Abstract Objectives In this study, we aimed to investigate the vascular response to an intravascular lithotripsy (IVL) shockwave balloon in a healthy porcine coronary artery model. Background IVL is a novel clinical technique for modifying heavily calcified atherosclerotic plaques. Methods A total of 24 porcine coronary arteries were treated with IVL or plain old balloon angioplasty (POBA). Histology, histomorphometry, quantitative coronary angiography analysis (QCA), and optical coherence tomography (OCT) were performed post-procedure and at 1-month follow-up (1M-FU). Results There was no significant difference in the late lumen loss and diameter stenosis (determined by QCA) and the minimal lumen area (evaluated by OCT) of the IVL and POBA groups at 1M-FU. Pathological analysis revealed that the lumen and neointima areas were similar between the two groups. However, the medial and adventitial layers were more prominent in the IVL than in the POBA group. The injury score and inflammation of the media and adventitia increased dramatically in the IVL group post-procedure and at 1M-FU. At 1M-FU, media fibrin deposition and adventitial fibrosis were also significantly increased in the IVL group. However, there was no significant difference in neointima fibrin deposition, endothelialization, and thrombosis between both groups. Layered separation of the media and adventitia was observed in the IVL group. Conclusion The findings indicate that the IVL balloon did not cause serious intimal hyperplasia and endothelial damage compared with the effects of POBA in the healthy coronary artery. However, shock waves may cause unique damage to the vascular media and adventitia in the coronary artery, which was not observed in the peripheral artery.Device introductionPathological image at 1M FU

Successful Application of PTRA in a Patient with AKI Due to Severe Unilateral Renal Artery Stenosis: A Case Report with 4-Year Follow-up and Review of Literature

Introduction: Renal artery stenosis (RAS) is defined by a decrease in the internal diameter of one or both of the renal arteries. This can lead to renal insufficiency. RAS mostly occurs due to atherosclerosis; however, other conditions can cause this complication. Case Presentation: We present a 66-year-old man who was initially presented with abrupt bilateral lower limbs and scrotal edema in Shahid Beheshti Hospital of Qom. The patient had been regularly visiting the nephrology clinic for mild CKD. Due to the increased levels of creatinine (Cr) and urea in serum, he underwent angiography with suspicion of RAS, and 99% stenosis was confirmed in the left renal artery. Immediately after the diagnosis, we subjected the patient to angioplasty. After removing the arterial stenosis, the patient passed 8 liters of urine during one day, and his symptoms, including generalized edema, weight gain, and dyspnea, were improved gradually. The patient was discharged after 8 days of hospitalization with dramatically improved kidney function and relatively good general conditions. Conclusions: This patient had an uncommon presentation for a unilateral RAS and significant narrowing in the healthy renal artery. Angioplasty and stenting yielded a satisfactory result as a definite and effective treatment, and the patient enjoyed a relatively normal life with preserved kidney function during 4 years of follow-up.