Blood Vessel Wall Research Articles

Linking wall shear stress and vorticity topologies: Toward a unified theory of cardiovascular flow disturbances

Broadening current knowledge about the complex relationship at the blood-vessel wall interface is a main challenge in hemodynamics research. Moving from the consideration that wall shear stress (WSS) provides a signature for the near-wall velocity dynamics and vorticity is considered the skeleton of fluid motion, here we present a unified theory demonstrating the existing link between surface vorticity (SV) and WSS topological skeletons, the latter recently emerged as a predictor of vascular disease. The analysis focused on WSS and SV fixed points, i.e., points where the fields vanish, as they play a major role in shaping the main vector field features. The theoretical analysis proves that: (i) all SV fixed points on the surface must necessarily be WSS fixed points, although with differences in nature and stability and (ii) a WSS fixed point is not necessarily a SV fixed point. In the former case, WSS fixed points are the consequence of flow patterns where only shear contributes to vorticity; in the latter case, WSS fixed points are the consequence of flow impingement to/emanation from the vessel wall. Moreover, fluid structures interacting with the wall characterized by zero or non-zero rotational momentum generate WSS fixed points of different nature/stability. High-fidelity computational fluid dynamics simulations in intracranial aneurysm models confirmed the applicability of the theoretical considerations. The presented unified theory unambiguously explains the mechanistic link between near-wall flow disturbances and the underlying intravascular flow features expressed in terms of vorticity, ultimately facilitating a clearer interpretation of the role of local hemodynamics in vascular pathophysiology.

Suppression of neointimal hyperplasia induced by arteriovenous anastomosis and balloon injury in rats by multimeric tumor necrosis factor-related apoptosis-inducing ligand

Excessive blood vessel wall thickening, known as intimal hyperplasia, can result from injury or inflammation and increase the risk of vascular diseases. Tumor necrosis factor-related apoptosis-inducing factor (TRAIL) plays key roles in tumor surveillance, autoimmune diseases, and apoptosis; however, its role in vascular stenosis remains controversial. Treatment with recombinant isoleucine zipper hexamerization domain soluble TRAIL (ILz(6):TRAIL) significantly inhibited the progression of neointimal hyperplasia (NH) induced by anastomosis of the carotid artery and jugular vein (AAV) dose dependently, and adenovirus expressing secretable ILz(6):TRAIL also inhibited NH induced by balloon injury in the femoral artery of rats. This study demonstrated the preventive and partial regressive effects of ILz(6):TRAIL on AAV- or balloon-induced NH.

Vascular Damage and Repair - Are Small-Diameter Vascular Grafts Still the "Holy Grail" of Tissue Engineering?

Cardiovascular diseases are the most important cause of morbidity and mortality in the civilized world. Stenosis or occlusion of blood vessels leads not only to events that are directly life-threatening, such as myocardial infarction or stroke, but also to a significant reduction in quality of life, for example in lower limb ischemia as a consequence of metabolic diseases. The first synthetic polymeric vascular replacements were used clinically in the early 1950s. However, they proved to be suitable only for larger-diameter vessels, where the blood flow prevents the attachment of platelets, pro-inflammatory cells and smooth muscle cells on their inner surface, whereas in smaller-diameter grafts (6 mm or less), these phenomena lead to stenosis and failure of the graft. Moreover, these polymeric vascular replacements, like biological grafts (decellularized or devitalized), are cell-free, i.e. there are no reconstructed physiological layers of the blood vessel wall, i.e. an inner layer of endothelial cells to prevent thrombosis, a middle layer of smooth muscle cells to perform the contractile function, and an outer layer to provide innervation and vascularization of the vessel wall. Vascular substitutes with these cellular components can be constructed by tissue engineering methods. However, it has to be admitted that even about 70 years after the first polymeric vascular prostheses were implanted into human patients, there are still no functional small-diameter vascular grafts on the market. The damage to small-diameter blood vessels has to be addressed by endovascular approaches or by autologous vascular substitutes, which leads to some skepticism about the potential of tissue engineering. However, new possibilities of this approach lie in the use of modern technologies such as 3D bioprinting and/or electrospinning in combination with stem cells and pre-vascularization of tissue-engineered vascular grafts. In this endeavor, sex-related differences in the removal of degradable biomaterials by the cells and in the behavior of stem cells and pre-differentiated vascular cells need to be taken into account. Key words: Blood vessel prosthesis, Regenerative medicine, Stem cells, Footprint-free iPSCs, sr-RNA, Dynamic bioreactor, Sex-related differences.

Detection of atherosclerotic plaques with HDL-like porphyrin nanoparticles using an intravascular dual-modality optical coherence tomography and fluorescence system

Atherosclerosis is the build-up of fatty plaques within blood vessel walls, which can occlude the vessels and cause strokes or heart attacks. It gives rise to both structural and biomolecular changes in the vessel walls. Current single-modality imaging techniques each measure one of these two aspects but fail to provide insight into the combined changes. To address this, our team has developed a dual-modality imaging system which combines optical coherence tomography (OCT) and fluorescence imaging that is optimized for a porphyrin lipid nanoparticle that emits fluorescence and targets atherosclerotic plaques. Atherosclerosis-prone apolipoprotein (Apo)e-/- mice were fed a high cholesterol diet to promote plaque development in descending thoracic aortas. Following infusion of porphyrin lipid nanoparticles in atherosclerotic mice, the fiber-optic probe was inserted into the aorta for imaging, and we were able to robustly detect a porphyrin lipid-specific fluorescence signal that was not present in saline-infused control mice. We observed that the nanoparticle fluorescence colocalized in areas of CD68+ macrophages. These results demonstrate that our system can detect the fluorescence from nanoparticles, providing complementary biological information to the structural information obtained from simultaneously acquired OCT.

Association of inflammatory markers and ultrasonographic indicators of endothelial (dys)function in humans

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Austrian Science Fund (FWF) Introduction It has been widely known that chronic inflammation is a crucial factor in the process of atherogenesis and atherosclerosis. Also, endothelial dysfunction presents the first and still reversible step of that process.(1) It is a challenge to find a laboratory marker whose levels would be informative about the extent of endothelial dysfunction and atherogenesis in humans. Purpose The aim of the present study was to determine associations between markers of chronic, low-grade inflammation and ultrasonographic indicators of endothelial (dys)function in healthy volunteers (H) and in patients with metabolic syndrome (MS). Methods Any kind of clinically manifest acute inflammatory or infectious disease, as well as chronic inflammatory, autoimmune or malignant disease was an exclusion criterion for participation. Serum levels of C-reactive protein (CRP) were measured using standard clinical chemistry analyser, and serum levels of interleukin-6 (IL-6) using electro-chemiluminescence immunoassay. Blood vessel wall function was quantified as flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD), which were measured automatically and continuously using the ultrasound device with linear probe (10 MHz) and the software for ultrasound blood vessel diameter analysis,(2) following currently valid guidelines.(3,4,5) Results A total of 130 individuals were enrolled in the study (65 H and 65 MS), with a median age of 56 (IQR 50.0, 60.0) years and 47.7% women in each group. CRP and IL-6 levels, although being very low and within the intervals that are considered normal in everyday clinical practice for both groups [CRP - H: 1.2 (0.6, 2.3), MS: 2.4 (1.2, 5.5) μg/mL; IL-6 - H: 2.3 (1.7, 3.0), MS: 4.1 (2.7, 6.8) pg/mL], were significantly higher in the MS compared to H (both p<0.001). The MS group also had significantly lower FMD (p=0.013) and NMD (p=0.033) compared to H. In H, IL-6 levels were significantly negatively correlated with FMD (r=-0.46, p<0.001), but not with NMD; whereas no significant associations of IL-6 levels with FMD or NMD were observed in the MS group. CRP levels were not significantly associated with FMD or NMD in neither the H nor MS group. Conclusion Higher IL-6 serum levels in the absence of acute inflammatory or infectious disease are significantly associated with lower FMD values among individuals with low risk for cardiovascular diseases, who are still considered healthy. Direct correlation is attenuated and lost among individuals with developed clinical signs of metabolic syndrome, probably due to its complex pathophysiology, as well as redundant and interdependent mechanisms contributing to the occurrence of endothelial dysfunction in such an environment. Further investigation on larger cohorts is needed to determine whether IL-6 serum levels could serve as a marker of endothelial dysfunction in individuals without clinically developed traditional risk factors and symptoms of cardiovascular disease.

Tuning Recombinant Perlecan Domain V to Regulate Angiogenic Growth Factors and Enhance Endothelialization of Electrospun Silk Vascular Grafts.

Synthetic vascular grafts are used to bypass significant arterial blockage when native blood vessels are unsuitable, yet their propensity to fail due to poor blood compatibility and progressive graft stenosis remains an intractable challenge. Perlecan is the major heparan sulfate (HS) proteoglycan in the blood vessel wall with an inherent ability to regulate vascular cell activities associated with these major graft failure modes. Here the ability of the engineered form of perlecan domain V (rDV) to bind angiogenic growth factors is tuned and endothelial cell proliferation via the composition of its glycosaminoglycan (GAG) chain is supported. It is shown that the HS on rDV supports angiogenic growth factor signaling, including fibroblast growth factor (FGF) 2 and vascular endothelial growth factor (VEGF)165, while both HS and chondroitin sulfate on rDV are involved in VEGF189 signaling. It is also shown that physisorption of rDV on emerging electrospun silk fibroin vascular grafts promotes endothelialization and patency in a murine arterial interposition model, compared to the silk grafts alone. Together, this study demonstrates the potential of rDV as a tunable, angiogenic biomaterial coating that both potentiates growth factors and regulates endothelial cells.

Computational study of haemodynamic change induced by the resuscitative endovascular balloon aortic occlusion

ABSTRACT Resusciative endovascular balloon aortic occlusion (REBOA) can be used in various surgical operations, especially in patients with hypotension and shock caused by traumatic main vascular rupture and massive haemorrhage. However, the hydrodynamic effects of surgery on aortic haemodynamics and organ perfusion are still unclear. Herein, computational fluid dynamic methods were used to evaluate the effect of balloon expansion and that of balloon-occluded aortic ratios on haemodynamics. The simulation shows that the balloon reduces the flow rate from the heart to the ruptured aorta. While reducing the flow rate of the aortic branches downstream of the balloon under conditions with fixed cardiac output, the balloon will increase the flow rate of the aortic branches upstream of the balloon. And the flow in the diastolic phase is more complicated than that of the systolic phase, and the vortex generated upstream of the balloon is more evident than that of the formed downstream. Moreover, when the inflation rate of the balloon changes rapidly, the flow rate of blood at the balloon changes suddenly accordingly, which generates a large additional pressure on the balloon. The pressure will spread upstream, thereby generating a blood hammer effect on the blood vessel wall.

Cationic Polysaccharides Bind to the Endothelial Cell Surface Extracellular Matrix Involving Heparan Sulfate.

Cationic polysaccharides have been extensively studied for drug delivery via the bloodstream, yet few have progressed to clinical use. Endothelial cells lining the blood vessel wall are coated in an anionic extracellular matrix called the glycocalyx. However, we do not fully comprehend the charged polysaccharide interactions with the glycocalyx. We reveal that the cationic polysaccharide poly(acetyl, arginyl) glucosamine (PAAG) exhibits the highest association with the endothelial glycocalyx, followed by dextran (neutral) and hyaluronan (anionic). Furthermore, we demonstrate that PAAG binds heparan sulfate (HS) within the glycocalyx, leading to intracellular accumulation. Using an in vitro glycocalyx model, we demonstrate a charge-based extent of association of polysaccharides with HS. Mechanistically, we observe that PAAG binding to HS occurs via a condensation reaction and functionally protects HS from degradation. Together, this study reveals the interplay between polysaccharide charge properties and interactions with the endothelial cell glycocalyx toward improved delivery system design and application.

Preparation of the new peptide drug ACTY116-loaded in situ forming implants and evaluation of its efficacy in pulmonary arterial hypertension and right ventricular hypertrophy induced by SU5416/hypoxia in mice.

There is a lack of effective therapeutic drugs for pulmonary arterial hypertension. Previous studies have demonstrated the positive cardiovascular system protective effects of the new peptide ACTY116. However, its stability in ordinary aqueous solution injections is poor and its half-life in the body is short, which has hindered the development of preparations. This study aimed to prepare in situ forming implants (ISFIs) of the peptide ACTY116 and investigate its impact on pulmonary arterial hypertension. We prepared ISFIs using NMP/TA as a solvent and PLGA as a polymer. These ISFIs exhibited low viscosity, low toxicity and sustained release properties. In a mouse model of pulmonary hypertension induced by SU5416/hypoxia, both ISFIs and ACTY116 peptides effectively reduced pulmonary hypertension, cardiac hypertrophy and pulmonary blood vessel wall thickness. In conclusion, this study highlights the potential of ACTY116 as a treatment for pulmonary arterial hypertension and suggests that incorporating it into an in-situ gel implant could be a promising option.

Ultrastructural investigation of iron oxide nanoparticles accumulation in the liver of common carp (Cyprinus carpio Linnaeus, 1758)

In recent years, the intensive production of nanoparticles with a wide application has led to their transfer to the environment, including the water ecosystem. The accumulation of nanoparticles in fish, causing various pathological changes in the host, raises certain concerns. In the current study, we investigated the penetration and bioaccumulation of Fe3O4 nanoparticles, in the liver of common carp (Cyprinus carpio Linnaeus, 1758). Common carp juveniles were exposed to Fe3O4 nanoparticles at concentrations of 10 and 100 mg. After 7 days, their livers were examined by light and transmission electron microscopes. Compared to normal fish's liver, after using a small concentration (10 mg) of nanoparticles, changes were observed in erythrocytes, hepatocytes, intracellular canaliculi, and bile ducts of the liver. At a high concentration (100 mg), the intensity of changes increased significantly. The liver's capsule was damaged, and a considerable number of hepatocytes were completely destroyed. Additionally, the walls of blood vessels and biliary ductule walls was notably disturbed. It was found that the intensity of pathologies occurring in the liver, increases proportionally with higher concentrations of nanoparticles. Confirmation via electron microscopic methods revealed that Fe3O4 nanoparticles, when administered with food to common carp, enter the fish's liver through erythrocytes localized in the lumen of blood vessels. From there, they traverse through the endothelium of vessels, proceed to hepatocytes, including cytoplasmic organelles, intracellular canaliculi, biliary ductules, and eventually reach the bile ducts. Fe3O4 nanoparticles in all structural elements of fish liver was up to 20 nm. Therefore, high concentrations of nanoparticles in the environment harms the bodies of aquatic organisms, including fish. The changes identified in the liver of common carp in the present study are valuable information in assessing possible risks to other components of the aquatic ecosystem and organisms.

Melatonin and mesenchymal stem cells co-administration alleviates chronic obstructive pulmonary disease via modulation of angiogenesis at the vascular-alveolar unit

Chronic obstructive pulmonary disease (COPD) is considered a severe disease mitigating lung physiological functions with high mortality outcomes, insufficient therapy, and pathophysiology pathways which is still not fully understood. Mesenchymal stem cells (MSCs) derived from bone marrow play an important role in improving the function of organs suffering inflammation, oxidative stress, and immune reaction. It might also play a role in regenerative medicine, but that is still questionable. Additionally, Melatonin with its known antioxidative and anti-inflammatory impact is attracting attention nowadays as a useful treatment. We hypothesized that Melatonin may augment the effect of MSCs at the level of angiogenesis in COPD. In our study, the COPD model was established using cigarette smoking and lipopolysaccharide. The COPD rats were divided into four groups: COPD group, Melatonin-treated group, MSC-treated group, and combined treated group (Melatonin–MSCs). We found that COPD was accompanied by deterioration of pulmonary function tests in response to expiratory parameter affection more than inspiratory ones. This was associated with increased Hypoxia inducible factor-1α expression and vascular endothelial growth factor level. Consequently, there was increased CD31 expression indicating increased angiogenesis with massive enlargement of airspaces and thinning of alveolar septa with decreased mean radial alveolar count, in addition to, inflammatory cell infiltration and disruption of the bronchiolar epithelial wall with loss of cilia and blood vessel wall thickening. These findings were improved significantly when Melatonin and bone marrow-derived MSCs were used as a combined treatment proving the hypothesized target that Melatonin might augment MSCs aiming at vascular changes.

The impact of temperature on vascular function in connection with vascular laser treatment

Pulsed dye lasers are used effectively in the treatment of psoriasis with long remission time and limited side effects. It is, however, not completely understood which biological processes underlie its favorable outcome. Pulsed dye laser treatment at 585-595 nm targets hemoglobin in the blood, inducing local hyperthermia in surrounding blood vessels and adjacent tissues. While the impact of destructive temperatures on blood vessels has been well studied, the effects of lower temperatures on the function of several cell types within the blood vessel wall and its periphery are not known. The aim of our study is to assess the functionality of isolated blood vessels after exposure to moderate hyperthermia (45 to 60°C) by evaluating the function of endothelial cells, smooth muscle cells, and vascular nerves. We measured blood vessel functionality of rat mesenteric arteries (n=19) by measuring vascular contraction and relaxation before and after heating vessels in a wire myograph. To this end, we elicited vascular contraction by addition of either high potassium solution or the thromboxane analogue U46619 to stimulate smooth muscle cells, and electrical field stimulation (EFS) to stimulate nerves. For measurement of endothelium-dependent relaxation, we used methacholine. Each vessel was exposed to one temperature in the range of 45-60°C for 30 seconds and a relative change in functional response after hyperthermia was determined by comparison with the response per stimulus before heating. Non-linear regression was used to fit our dataset to obtain the temperature needed to reduce blood vessel function by 50% (Half maximal effective temperature, ET50). Our findings demonstrate a substantial decrease in relative functional response for all three cell types following exposure to 55°C-60°C. There was no significant difference between the ET50 values of the different cell types, which was between 55.9°C and 56.9°C (P>0.05). Our data show that blood vessel functionality decreases significantly when exposed to temperatures between 55°C-60°C for 30 seconds. The results show functionality of endothelial cells, smooth muscle cells, and vascular nerves is similarly impaired. These results help to understand the biological effects of hyperthermia and may aid in tailoring laser and light strategies for selective photothermolysis that contribute to disease modification of psoriasis after pulsed dye laser treatment.

Shear and normal stresses of electroosmotic magnetized physiological nanofluid on curved artery with moderate Reynolds number: application on electroshock therapy

PurposeStudying the shear stress and pressure resulting on the walls of blood vessels, especially during high-pressure cases, which may lead to the explosion or rupture of these vessels, can also lead to the death of many patients. Therefore, it was necessary to try to control the shear and normal stresses on these veins through nanoparticles in the presence of some external forces, such as exposure to some electromagnetic shocks, to reduce the risk of high pressure and stress on those blood vessels. This study aims to examines the shear and normal stresses of electroosmotic-magnetized Sutterby Buongiorno’s nanofluid in a symmetric peristaltic channel with a moderate Reynolds number and curvature. The production of thermal radiation is also considered. Sutterby nanofluids equations of motion, energy equation, nanoparticles concentration, induced magnetic field and electric potential are calculated without approximation using small and long wavelengths with moderate Reynolds numbers.Design/methodology/approachThe Adomian decomposition method solves the nonlinear partial differential equations with related boundary conditions. Graphs and tables show flow features and biophysical factors like shear and normal stresses.FindingsThis study found that when curvature and a moderate Reynolds number are present, the non-Newtonian Sutterby fluid raises shear stress across all domains due to velocity decay, resulting in high shear stress. Additionally, modest mobility increases shear stress across all channel domains. The Sutterby parameter causes fluid motion resistance, which results in low energy generation and a decrease in the temperature distribution.Originality/valueEquations of motion, energy equation, nanoparticle concentration, induced magnetic field and electric potential for Sutterby nano-fluids are obtained without any approximation i.e. the authors take small and long wavelengths and also moderate Reynolds numbers.

Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction.

Sigmar1 is a ubiquitously expressed, multifunctional protein known for its cardioprotective roles in cardiovascular diseases. While accumulating evidence indicate a critical role of Sigmar1 in cardiac biology, its physiological function in the vasculature remains unknown. In this study, we characterized the expression of Sigmar1 in the vascular wall and assessed its physiological function in the vascular system using global Sigmar1 knockout (Sigmar1-/-) mice. We determined the expression of Sigmar1 in the vascular tissue using immunostaining and biochemical experiments in both human and mouse blood vessels. Deletion of Sigmar1 globally in mice (Sigmar1-/-) led to blood vessel wall reorganizations characterized by nuclei disarray of vascular smooth muscle cells, altered organizations of elastic lamina, and higher collagen fibers deposition in and around the arteries compared to wildtype littermate controls (Wt). Vascular function was assessed in mice using non-invasive time-transit method of aortic stiffness measurement and flow-mediated dilation (FMD) of the left femoral artery. Sigmar1-/- mice showed a notable increase in arterial stiffness in the abdominal aorta and failed to increase the vessel diameter in response to reactive-hyperemia compared to Wt. This was consistent with reduced plasma and tissue nitric-oxide bioavailability (NOx) and decreased phosphorylation of endothelial nitric oxide synthase (eNOS) in the aorta of Sigmar1-/- mice. Ultrastructural analysis by transmission electron microscopy (TEM) of aorta sections showed accumulation of elongated shaped mitochondria in both vascular smooth muscle and endothelial cells of Sigmar1-/- mice. In accordance, decreased mitochondrial respirometry parameters were found in ex-vivo aortic rings from Sigmar1 deficient mice compared to Wt controls. These data indicate a potential role of Sigmar1 in maintaining vascular homeostasis.

Ethyl alcohol. Influence on the dynamics of blood supply of skin and other soft tissues during their sudden cooling

It is shown that in norm (i.e. in sober people in the absence of ethyl alcohol in blood) sudden local cooling of skin and soft tissues of different parts of the body from +37 to +18 °С and below (but not below 0 °С) causes in the cooled tissues 2-phase change in the value of blood vessels tone, their blood filling, intensity of blood supply and feeling of painfulness. Thus from the first seconds of cooling the tone of blood vessels of muscular type begins to increase, their blood filling begins to decrease, skin color lightens and soon in the cooled area of the body there is a feeling of acute soreness. After a few tens of seconds of cooling, the spasm of blood vessels reaches maximum values, their filling with blood decreases to a minimum, the skin turns white, and the soreness reaches maximum values. These changes persist at their peak for a few minutes, after which they begin to disappear, despite the persisting hypothermia. But then, after 10-15 minutes of cooling, hyperemia inevitably develops in the hypothermia zone, as a result of which the soreness disappears and the skin reddens. It is established that in the norm, sudden cooling of tissues causes irritation of temperature receptors located in them. The resulting excitation of temperature receptors causes reflex spasm of blood vessels, which has an adaptive value, as it is evolutionarily developed for temperature homeostasis of warm-blooded organism. It has been found out that acute painfulness accompanying cold spasm of blood vessels arises due to mechanical squeezing of pain receptors located under the muscular layer in the wall of blood vessels. On the other hand, the presence of ethyl alcohol in the blood (the presence of alcohol intoxication) fundamentally changes the dynamics of blood supply of tissues at their sudden cooling: during cooling, blood vessels expand and overflow with blood without the initial phase of spasm and the appearance of a sense of pain. At the same time, hyperemia persists not only throughout the cooling period, but also after it. In other words, alcohol intoxication is manifested by the immediate development of hyperemia and redness of the skin in the cooled area of the body without the initial spasm of blood vessels, the appearance of a feeling of soreness and pallor of the skin in the area of cooling.

Inhibition of vascular calcification by Compound Danshen Dripping Pill through multiple mechanisms

BackgroundVascular calcification refers to the abnormal accumulation of calcium in the walls of blood vessels and is a risk factor often overlooked in cardiovascular disease. However, there is currently no specific drug for treating vascular calcification. Compound Danshen Dripping Pill (CDDP) is widely used to treat cardiovascular diseases, but its effect on vascular calcification has not been reported. PurposeWe investigated the effects of CDDP on vascular calcification in ApoE−/− mice and in vitro and elucidated its mechanism of action. Study designFirstly, we found that CDDP has the potential to improve calcification based on network pharmacology analysis. Then, we performed the following experiments: in vivo, ApoE−/− mice were fed a high-fat diet randomly supplemented with CDDP for 16 weeks. Atherosclerosis and vascular calcification were determined. In vitro, human aortic smooth muscle cells (HASMCs), human umbilical vein endothelial cells (HUVECs), and human aortic endothelial cells (HAECs) were used to determine the mechanisms for CDDP-inhibited vascular calcification. ResultsIn this study, we observed that CDDP reduced intimal calcification in atherosclerotic lesions of ApoE-deficient mice fed a high-fat diet, as well as the calcification in cultured SMCs and ECs. Mechanistically, CDDP inhibited the Wnt/β-catenin pathway by up-regulating the expression of DKK1 and LRP6, which are upstream inhibitors of Wnt, leading to a reduction in the expression of osteoblastic transition markers (ALP, OPN, BMP2, and RUNX2). Furthermore, CDDP enhanced the secretion of DKK1, which plays a role in mediating EC-SMC crosstalk in calcification. Additionally, VC contributes to vascular aging by inhibiting Sirt1 and increasing senescence parameters (SA-β-gal, p21, and p16). However, CDDP reversed these changes by activating Sirt1. CDDP also reduced the levels of pro-inflammatory cytokines and the senescence-associated secretory phenotype in vivo and in vitro. ConclusionsOur study suggests that CDDP reduces vascular calcification by regulating the DKK1/LRP6/β-catenin signaling pathway in ECs/SMCs and interactions with the crosstalk of ECs and SMCs. It also reduces the senescence of ECs/SMCs, contributing to the Sirt1 activation, indicating CDDP's novel role in ameliorating vascular calcification.

Critical gene signature and immunological characterization in peripheral vascular atherosclerosis: novel insights from mendelian randomization and transcriptomics.

Peripheral vascular atherosclerosis (PVA) is a chronic inflammatory disease characterized by lipid accumulation in blood vessel walls, leading to vessel narrowing and inadequate blood supply. However, the molecular mechanisms underlying PVA remain poorly understood. In this study, we employed a combination of Mendelian randomization (MR) analysis and integrated transcriptomics to identify the critical gene signature associated with PVA. This study utilized three public datasets (GSE43292, GSE100927 and GSE28829) related to peripheral vascular atherosclerosis obtained from the Gene Expression Omnibus database. Instrumental variables (IVs) were identified through expression quantitative trait loci (eQTL) analysis, and two-sample MR analysis was performed using publicly available summary statistics. Disease critical genes were identified based on odds ratios and intersected with differentially expressed genes in the disease dataset. GSE28829 dataset was used to validate the screened disease critical genes. Functional enrichment analysis, GSEA analysis, and immune cell infiltration analysis were performed to further characterize the role of these genes in peripheral vascular atherosclerosis. A total of 26,152 gene-related SNPs were identified as IVs, and 242 disease-associated genes were identified through MR analysis. Ten disease critical genes (ARHGAP25, HCLS1, HVCN1, RBM47, LILRB1, PLAU, IFI44L, IL1B, IFI6, and CFL2) were significantly associated with peripheral vascular atherosclerosis. Functional enrichment analysis using KEGG pathways revealed enrichment in the NF-kappa B signaling pathway and osteoclast differentiation. Gene set enrichment analysis further demonstrated functional enrichment of these genes in processes related to vascular functions and immune system activation. Additionally, immune cell infiltration analysis showed differential ratios of B cells and mast cells between the disease and control groups. The correlations analysis highlights the intricate interplay between disease critical genes and immune cells associated with PVA. In conclusion, this study provides new insights into the molecular mechanisms underlying PVA by identifying ten disease critical genes associated with the disease. These findings, supported by differential expression, functional enrichment, and immune system involvement, emphasize the role of these genes in vascular function and immune cell interactions in the context of PVA. These findings contribute to a better understanding of PVA pathogenesis and offer potential targets for further mechanistic exploration and therapeutic interventions.

Accurate Temperature Reconstruction in Radiofrequency Ablation for Atherosclerotic Plaques Based on Inverse Heat Transfer Analysis.

Radio frequency ablation has emerged as a widely accepted treatment for atherosclerotic plaques. However, monitoring the temperature field distribution in the blood vessel wall during this procedure presents challenges. This limitation increases the risk of endothelial cell damage and inflammatory responses, potentially leading to lumen restenosis. The aim of this study is to accurately reconstruct the transient temperature distribution by solving a stochastic heat transfer model with uncertain parameters using an inverse heat transfer algorithm and temperature measurement data. The nonlinear least squares optimization method, Levenberg-Marquardt (LM), was employed to solve the inverse heat transfer problem for parameter estimation. Then, to improve the convergence of the algorithm and reduce the computational resources, a method of parameter sensitivity analysis was proposed to select parameters mainly affecting the temperature field. Furthermore, the robustness and accuracy of the algorithm were verified by introducing random noise to the temperature measurements. Despite the high level of temperature measurement noise (ξ = 5%) and larger initial guess deviation, the parameter estimation results remained closely aligned with the actual values, with an overall ERMS consistently below 0.05. The absolute errors between the reconstruction temperature at the measurement points TC1, TC2, and TC3, and the actual temperature, remained within 0.33 °C, 2.4 °C, and 1.17 °C, respectively. The Levenberg-Marquardt algorithm employed in this study proficiently tackled the ill-posed issue of inversion process and obtained a strong consistency between the reconstructed temperature the actual temperature.

Design of composite puncture blood collection system and research on puncture force.

Venous blood collection testing is one of the most commonly used medical diagnostic methods. Compared with conventional venous blood collection, robotic collection can reduce needle-stick injuries, medical staff workload, and infection risk; allow doctor-patient isolation; and improve collection reliability. Existing venous blood collection robots use rigid puncture needles, which can easily puncture the lower wall of blood vessels, causing vessel damage and collection failure. This paper proposes a bionic blood collection strategy based on a composite puncture needle that mimics the structure and function of mosquito mouthparts. A bionic composite puncture needle insertion system with puncture-force sensing was designed, and venipuncture forces were simulated and mathematically modelled. A prototype insertion system was built and used in an experiment, which demonstrated effective composite puncture blood collection and explored the factors influencing puncture force. Puncture force decreases with increased puncture speed and angle and with a decreased needle diameter. This provides a basis for optimising the parameters of blood collection robots.

Modeling pulsed dye laser treatment of psoriatic plaques by combining numerical methods and image-derived lesion morphologies.

Knowledge of the physical effects of pulsed dye laser (PDL) treatment of psoriatic lesions is essential in unraveling the remedial mechanisms of this treatment and hence also in maximizing in its disease-modifying potential. Therefore, the main objective of this study was to provide estimates of these physical effects (for laser wavelengths of 585and 595 nm), with the aim of identifying pathogenic processes that may be affected by these conditions. We modeled the laser light propagation and subsequent photothermal heating by numerically solving the transient diffusion and heat equations simultaneously. To this end, we used the finite element method in conjunction with an image-derived psoriatic lesion morphology (which was defined by segmenting blood vessels from a confocal microscopy image of a fluorescently labeled section of a 3 mm punch biopsy of a psoriatic lesion). The resulting predictions of the generated temperature field within the lesion were then used to assess the possibility of stalling or arresting some suspected pathogenic processes. According to our results, it is conceivable that perivascular nerves are thermally denatured, as almost all locations that reach 60°C were found to be within 18 µm (at 585 nm) and 11 µm (at 595 nm) of a blood vessel wall. Furthermore, activation of TRPV1 and TRPV2 channels in perivascular neuronal and immune cells is highly likely, since a critical temperature of 43°C is generated at locations within up to 350 µm of a vessel wall (at both wavelengths) and sustained for up to 700 ms (at 585 nm) and 40 ms (at 595 nm), while a critical temperature of 52°C is reached by locations within 80 µm (at 585 nm) and 30 µm (at 595 nm) of a vessel wall and sustained for up to 100 ms (at 585 nm) and 30 ms (at 595 nm). Finally, we found that the blood vessel coagulation-inducing temperature of 70°C is sustained in the vascular epithelium for up to 19and 5 ms at 585and 595 nm, respectively, rendering partial or total loss of vascular functionality a distinct possibility. The presented approach constitutes a useful tool to provide realistic estimates of the photothermal effects of PDLtreatment of psoriatic plaques (as well as other selective photothermolysis-based treatments), yielding information that is essential in guiding future experimental studies towardunraveling the remedial mechanisms of these treatments.