Early Stages Of Atherosclerosis Research Articles

Improving of the biomechanical parameters in an experimental animal abdominal aorta model of early stage atherosclerosis using ultrasound- guided extracorporeal low- level focused sonotherapy

Improving of the biomechanical parameters in an experimental animal abdominal aorta model of early stage atherosclerosis using ultrasound- guided extracorporeal low- level focused sonotherapy

Allogeneic Adipose-Derived Mesenchymal Stem Cell Transplantation Alleviates Atherosclerotic Plaque by Inhibiting Ox-LDL Uptake, Inflammatory Reaction and Endothelial Damage in Rabbits.

Atherosclerosis (AS) is a chronic inflammatory disease of arteries fueled by lipids. It is a major cause of cardiovascular morbidity and mortality. Mesenchymal stem cells have been used for the treatment of atherosclerotic lesions. Adipose-derived stem cells (ADSCs) have been shown to regulate the activation state of macrophages and exhibit anti-inflammatory capabilities. However, the effect of allogeneic ADSCs in the treatment of AS have not been investigated. In this study, the early treatment effect and preliminary mechanism analysis of allogeneic rabbit ADSCs intravenous transplantation were investigated in a high-fat diet rabbit model. The polarization mechanism of rabbit ADSCs on the macrophage was further analyzed in vitro. Compared with the model group, blood lipid levels declined, the plaque area, oxidized low-density lipoprotein (ox-LDL) uptake, scavenger receptor A1 and cluster of differentiation (CD) 36 levels were all significantly reduced, and the accumulation of inflammatory M1 macrophages, apoptosis, interleukin (IL)-6 and tumor necrosis factor (TNF)-α expression were decreased. The endothelial cells (CD31), M2 macrophages, IL-10 and the transforming growth factor (TGF)-β levels increased. In vitro, ADSCs can promote the M1 macrophage phenotypic switch toward the M2 macrophage through their secreted exosomes, and the main mechanism includes increasing arginase 1 expression and IL-10 secretion, declining inducible nitric oxide synthase (iNOS) expression and TNF-α secretion, and activating the STAT6 pathway. Therefore, allogeneic rabbit ADSC transplantation can transmigrate to the aortic atherosclerotic plaques and show a good effect in lowering blood lipids and alleviating atherosclerotic plaque in the early stage of AS by inhibiting ox-LDL uptake, inflammatory response, and endothelial damage.

Early prediction of atherosclerosis diagnosis with medical ambient intelligence.

Atherosclerosis is a chronic vascular disease that poses a significant threat to human health. Common diagnostic methods mainly rely on active screening, which often misses the opportunity for early detection. To overcome this problem, this paper presents a novel medical ambient intelligence system for the early detection of atherosclerosis by leveraging clinical data from medical records. The system architecture includes clinical data extraction, transformation, normalization, feature selection, medical ambient computation, and predictive generation. However, the heterogeneity of examination items from different patients can degrade prediction performance. To enhance prediction performance, the "SEcond-order Classifier (SEC)" is proposed to undertake the medical ambient computation task. The first-order component and second-order cross-feature component are then consolidated and applied to the chosen feature matrix to learn the associations between the physical examination data, respectively. The prediction is lastly produced by aggregating the representations. Extensive experimental results reveal that the proposed method's diagnostic prediction performance is superior to other state-of-the-art methods. Specifically, the Vitamin B12 indicator exhibits the strongest correlation with the early stage of atherosclerosis, while several known relevant biomarkers also demonstrate significant correlation in experimental data. The method proposed in this paper is a standalone tool, and its source code will be released in the future.

Vascular Ageing: Mechanisms, Risk Factors, and Treatment Strategies.

Ageing constitutes the biggest risk factor for poor health and adversely affects the integrity and function of all the cells, tissues, and organs in the human body. Vascular ageing, characterised by vascular stiffness, endothelial dysfunction, increased oxidative stress, chronic low-grade inflammation, and early-stage atherosclerosis, may trigger or exacerbate the development of age-related vascular diseases, which each year contribute to more than 3.8 million deaths in Europe alone and necessitate a better understanding of the mechanisms involved. To this end, a large number of recent preclinical and clinical studies have focused on the exponential accumulation of senescent cells in the vascular system and paid particular attention to the specific roles of senescence-associated secretory phenotype, proteostasis dysfunction, age-mediated modulation of certain microRNA (miRNAs), and the contribution of other major vascular risk factors, notably diabetes, hypertension, or smoking, to vascular ageing in the elderly. The data generated paved the way for the development of various senotherapeutic interventions, ranging from the application of synthetic or natural senolytics and senomorphics to attempt to modify lifestyle, control diet, and restrict calorie intake. However, specific guidelines, considering the severity and characteristics of vascular ageing, need to be established before widespread use of these agents. This review briefly discusses the molecular and cellular mechanisms of vascular ageing and summarises the efficacy of widely studied senotherapeutics in the context of vascular ageing.

Numerical study on biomechanics in bifurcated coronary artery with plaques of different scenarios considering cardiac motion

During the development of atherosclerosis, plaques of different scenarios are formed at the bifurcation of the coronary arteries, which causes patients to exhibit different symptoms. The purpose of this study was to analyze the effect of plaque in different scenarios on the biomechanics of the bifurcated left coronary artery. In order to reflect the blood flow in the atherosclerotic coronary arteries more exactly, five vivid coronary artery models with a plaque of different scenarios are created based on Computed Tomography (CT) and anatomical images. Furthermore, the three-dimensional artery motion equations are created and fitted to the distal end of the coronary artery to describe the cardiac motion. The reciprocal influence of fluid and solid is also taken into account, constituting a fluid–structure interaction study. The risk of plaques in different scenarios was assessed by analyzing different physical parameters of arteries and blood. The results show that the effect of plaque on arterial stress is concentrated in the proximal coronary artery while the impact on blood flow is mainly focused on the narrow area and downstream of plaque. Wall shear stress promotes plaque growth in the early stages of atherosclerosis and drives plaque rupture after stenosis formation. There is a negative correlation between relative residence time and the degree of coronary artery stenosis and stiffness.

Pengaruh Ekstrak Buah Bakau (Rhizophora sp) terhadap Ekspresi Monocyte Chemoattractant Protein-1 pada Aorta Tikus Aterosklerosis

Atherosclerosis is an atheromatous plaque that protrudes into and clogs blood vessels. This study aimed to analyze the effect of Rhizophora sp extract on the expression of Monocyte Chemoattractant Protein-1 (MCP-1) in the early stages of atherosclerosis in rats fed an atherogenic diet. Eighteen abdominal aortic paraffin blocks of white rats were used, consisting of 3 groups: normal diet (K1), atherogenic diet (K2), and atherogenic diet and Rhizophora sp extract (K3). The effect of Rhizophora sp extract was assessed by immunohistochemical examination. MCP-1 expression was calculated in 5 fields of view, then analyzed using Photoshop Image Analysis. The results of this study indicated that administration of Rhizophora sp extract reduced MCP-1 expression in K3 compared to K2 (0.155±0.075 vs 0.246±0.097) although this result was not statistically significant. In conclusion, Rhizophora sp extract has the ability to inhibit MCP-1 expression in the aorta of rats fed an atherogenic diet.

Association of Serum Cystatin C Level With Carotid Arterial Wall Elastic Resistance as a Potential Marker for Detection of Early Stage Atherosclerosis.

Early diagnosis of atherosclerosis is exigent in patients with known cardiovascular disease (CVD) risk factors. During the initial phases of atherosclerosis, appearance of plaques can be detected by the ultrasonic phased tracking method which measures the arterial wall elasticity. However, reliable and easily available biochemical markers are not evaluated in the diagnosis of early-stage atherosclerosis. So the current study was carried out to assess the serum cystatin C level as an atherosclerotic marker, by evaluating its association with carotid arterial elastic modulus using the phased tracking method. A cross-sectional study was conducted on 115 patients havingrisk factors for atherosclerosis but not meeting carotid intima-media thickness (IMT) criteria. The early-stage atherosclerosis was detected by using the ultrasonic phased tracking method and the patients were divided based onlow and high carotid elastic modulus. Serum levels of cystatin-C were measured in association with IMT, and elastic modulus was calculated using a novel method. This study also put forth the evaluation ofthe sensitivity and specificity of cystatin C for early diagnosis of atherosclerosis. Cystatin C was strongly related to carotid elasticity (r=0.650). Based on multi-linear regression analysis, cystatin C showed significant association with carotid elasticity (β=0.509; p<0.001). It also displayed significant positive association with high carotid elastic modulus (β=0.511; p=0.02). Cystatin C showed a sensitivity of 85% in the prediction ofhigh carotid elastic modulus. For patients who are at risk to evolve atherosclerosis but are not evident with arterial plaques, cystatin C exhibits a significant association with carotid wall elastic modulus, which eases the detection of atherosclerosis. Thus, cystatin C is a potential biochemical marker for early diagnosis of atherosclerosis.

Duplex Responsive Nanoplatform with Cascade Targeting for Atherosclerosis Photoacoustic Diagnosis and Multichannel Combination Therapy.

The culprits of atherosclerosis are endothelial damage, local disorders of lipid metabolism, and progressive inflammation. Early atherosclerosis is typically difficult to diagnose in time due to the lack of obvious symptoms, thus missing the best period of treatment. In this work, a π-conjugated polymer (PMeTPP-MBT) based on 3,6-bis(4-methylthiophen-2-yl)-2,5-bis(2-octyldodecyl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione is designed as a novel photoacoustic contrast agent. On this basis, an intelligent responsive theranostic nanoplatform (PA/ASePSD) combining astaxanthin and SS-31 peptide and loading with PMeTPP-MBT is developed. The high affinity between the dextran shell with the broken endothelial surface VCAM-1 and CD44 confers active targeting of PA/ASePSD to atherosclerotic lesions. High levels of ROS in the acidic plaque microenvironment act as an intelligent cascade switch to achieve controlled release of astaxanthin, SS-31 peptide, and PMeTPP-MBT for non-invasive photoacoustic diagnosis, as well as plaque inhibition mediated by anti-inflammation and multichannel regulation (including ABCA1, ABCG1, CD36, and LOX-1) of lipid metabolism. Both in vitro and in vivo evaluations confirm the impressive anti-atherosclerotic capability and the accurate photoacoustic diagnosis of PA/ASePSD nanoparticles, thus promising a candidate for early-stage atherosclerosis theranostics.

Millet shell polyphenols ameliorate atherosclerosis development by suppressing foam cell formation

Polyphenols are bioactive compounds that occur naturally in plants, and they are widely used for disease prevention and health maintenance. In present study, the effects of millet shell polyphenols (MSPs) in thwarting atherosclerosis were explored. The results found that MSPs effectively inhibited the ability of macrophages to phagocytose lipids, and reduced the secretion of inflammatory factors IL-1β and TNF-α by obstructing the expression of STAT3 and NF-κB in macrophages. Eventually, MSPs hindered the formation of macrophage-derived foam cells. On the other hand, MSPs promoted the transformation of HASMCs from synthesis to contraction by regulating the gene expression levels of smooth muscle myosin heavy chain (SMMHC), desmin (DES), smoothelin (SMTN) and elastin (ELN). Lipid phagocytosis inhibited along with this process, thereby reducing the formation of smooth muscle cell-derived foam cells. In addition, experiments in ApoE−/− mice also showed that MSPs increased high-density lipoprotein cholesterol (HDL-C). Collectively, MSPs play a role in preventing atherosclerosis by impeding foam cell production. This study offers an integrative strategy for thwarting plaque formation in the early stages of atherosclerosis in cardiovascular disease.

HClO-triggered interventional probe enabled early detection and intervention of atherosclerosis.

Foam cell formation and further accumulation in the subendothelial space of the vascular wall is a hallmark of early atherosclerosis (AS). Targeting foam cell formation can be a promising approach for the early detection and prevention of AS. However, only a few studies have actually examined foam cells in vivo, and most methods combined nanotechnology with angiography, which is complex and could cause further damage to the endothelium. Herein, based on methylene blue, a biosafe NIR dye approved by the FDA, an interventional probe (HMB-NA@Mp) triggered by hypochlorous acid (HClO) was designed for imaging foam cells easily, safely, and effectively in the early stage of AS. Here, encapsulation of the probe by foam cells targeted platelet membrane (Mp) increased probe targeting and reduced toxicity. Cell and animal experimental results showed that the probe could accumulate at the lesion site and significantly enhance fluorescence in the early AS model group. Remarkably, at the same time, it could also release the metabolite niacin, which played a role in inhibiting atherosclerosis. Thus, HMB-NA@Mp is expected to be a powerful means for the early detection and timely intervention of early AS in the absence of clinical symptoms.

Targeting Theranostics of Atherosclerosis by Dual-Responsive Nanoplatform via Photoacoustic Imaging and Three-In-One Integrated Lipid Management.

Atherosclerosis, as a life-threatening cardiovascular disease with chronic inflammation and abnormal lipid enrichment, is often difficult to treat timely due to the lack of obvious symptoms. In this work, a theranostic nanoplatform is constructed for the noninvasive in vivo diagnosis, plaque-formation inhibition, and the lesion reversal of atherosclerosis. A three-in-one therapeutic complex is constructed and packaged along with a polymeric photoacoustic probe into nanoparticles named as PLCDP@PMH, which indicates an atherosclerosis-targeting accumulation and a reactive oxygen species (ROS)/matrix metalloproteinase (MMP) dual-responsive degradation. The photoacoustic probe suggests a lesion-specific imaging on atherosclerotic mice with an accurate and distinct recognition of plaques. At the same time, the three-in-one complex performs an integrated lipid management through the inhibition of macrophages M1-polarization, liver X receptor (LXR)-mediated up-regulation of ATP-binding cassette transporter A1/G1 (ABCA1/G1) and the cyclodextrin-assisted lipid dissolution, which lead to the reduced lipid uptake, enhanced lipid efflux, and actuated lipid removal. The in vivo evaluations reveal that PLCDP@PMH can suppress the lesion progression and further reverse the formed plaques under a diet without high fat. Hence, PLCDP@PMH provides a candidate for the theranostics of early-stage atherosclerosis and delivers an impressive potential on the reversal of formed atherosclerotic lesions.

Assessing the Progression of Early Atherosclerosis Mice Using a Fluorescence Nanosensor for the Simultaneous Detection and Imaging of pH and Phosphorylation

AbstractThe inflammatory microenvironment involves changes in pH and protein phosphorylation state and is closely related to the occurrence and development of atherosclerosis (AS). Herein, we constructed a dual‐detection fluorescence nanosensor PCN‐NP‐HPZ based on post modification of MOFs, which realized the simultaneous detection and imaging of pH and phosphorylation through the pH‐sensitive group piperazine and the ZrIV node of the MOFs. The sensors were used to monitor changes in blood pH and phosphate levels at different time stages during atherosclerotic plaque formation. Two‐photon fluorescence imaging was also performed in the vascular endothelium. Blood tests combined with two‐photon fluorescence images indicated that in the early stage of AS, blood and tissue pH levels were lower than that of the normal mice, while phosphate and tissue phosphorylation levels were higher than that of the normal mice. The present study provides a new analysis method for the assessment of early atherosclerotic disease.

Assessing the Progression of Early Atherosclerosis Mice Using a Fluorescence Nanosensor for the Simultaneous Detection and Imaging of pH and Phosphorylation.

The inflammatory microenvironment involves changes in pH and protein phosphorylation state and is closely related to the occurrence and development of atherosclerosis (AS). Herein, we constructed a dual-detection fluorescence nanosensor PCN-NP-HPZ based on post modification of MOFs, which realized the simultaneous detection and imaging of pH and phosphorylation through the pH-sensitive group piperazine and the ZrIV node of the MOFs. The sensors were used to monitor changes in blood pH and phosphate levels at different time stages during atherosclerotic plaque formation. Two-photon fluorescence imaging was also performed in the vascular endothelium. Blood tests combined with two-photon fluorescence images indicated that in the early stage of AS, blood and tissue pH levels were lower than that of the normal mice, while phosphate and tissue phosphorylation levels were higher than that of the normal mice. The present study provides a new analysis method for the assessment of early atherosclerotic disease.

Early stage atherosclerosis regression using combined sonotherapy and mitoxantrone-mediated sonoporation therapy

Abstract Background In atherosclerosis, local inflammation and associated macrophage activity can lead to foam cell-rich plaque formation, which results to plaque rupture and thrombosis, making inflammation an important therapeutic target in cardiovascular disease. The early stage of atherosclerosis is characterized by the accumulation of low-density lipoprotein (LDL) droplets, leading to the creation of foam cells. Foam cells are generated by uncontrolled uptake of modified LDL, especially oxidized LDL (oxLDL). Purpose In this study, we developed an experimental focused ultrasound-based combined sonotherapy and sonoporation therapy system, and investigated its effectiveness on macrophage-derived foam cells reduction, wherein a high resolution diagnostic ultrasound is adjuncted with combination therapy system, with a goal of increased safety. Methods Briefly, New Zealand white rabbits underwent primary balloon dilatation injury at the right common carotid artery followed by a 1.5% cholesterol-rich diet injury for three weeks. Histopathology results showed the early stage atherosclerosis formation in all of the rabbits' arteries. Then common carotid arteries of the treatment group at the lesion region, treated using extracorporeal low-level pulsed-focused ultrasound (P=11 W, F=1.1 MHz, DF=50%) sonotherapy accompanied by mitoxantrone-loaded PESDA (Perfluorocarbon-Exposed Sonicated Dextrose Albumin) microbubbles (100 ml/kg, 2–5x105 bubbles/ml)-mediated sonoporation therapy. Foam cells density were evaluated in the treatment group compared with the other groups using B-mode ultrasonography and histopathology. Results Results from B-mode ultrasonography and histopathology showed a significant reduction in the mean value for immune cells and foam cells density within the early stage atherosclerotic lesion in the treatment group compared with the other groups (p&amp;lt;0.05). Conclusion Enhanced sonoporation effect of ultrasound, induced by collapsed PESDA microbubbles accompanied by anti-inflammatory effect of sonotherapy and antineoplastic and cytotoxic effect of mitoxantrone can cause to reduce the immune cells and foam cells density within the lesion. These finding provide the basis for developing low-level pulsed-focused ultrasound-based combined sonotherapy and sonoporation therapy for a successful clinical application in the treatment of the early stage atherosclerosis. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Mehrad Research Lab

High- vs. low-intensity statin therapy and changes in coronary artery calcification density after one year

Abstract Introduction High-dose statin therapy (HIST) halts coronary plaque progression and reduces the risk of cardiovascular events by increasing atheroma calcification. The Agatston score is well established in the clinical routine for assessment of coronary artery calcification using non-contrast computed tomography. However, randomized controlled trials failed to detect an influence of HIST vs. low-to-intermediate statin therapy (LIST) on the Agatston and CAC volume score after one year. Coronary plaques with lower density including spotty calcifications may represent dynamic and early stages of atherosclerosis. We evaluated whether CAC density differentiates in HIST- vs. LIST-treated patients after one year. Methods The meta-analysis contains data from two prospective, randomized, double-blind studies (BELLES, EBEAT) that were designed to detect CAC changes after one year comparing HIST vs. LIST. In both studies, patient's coronary calcification burden was measured at baseline and one-year follow-up using electron beam computed tomography (EBCT). Patients data were pooled and stratified by intensity of statin therapy. Furthermore, the cohort was divided into several subgroup analyses, accounting for LDL-Cholesterol reduction, initial Agatston score and a consistent number of lesions. Results Data from 852 patients, 66% female were included. The amount of CAC overall increased after 1 year [Agatston score: 169.3 (80.0, 377.1) vs. 214.9 (95.4, 450.0); p&amp;lt;0.0001NP; volume score: 292.1±445.4 vs. 355.5±482.4; p&amp;lt;0.0001; number of lesions: 6 (3,10) vs. 7 (4,12); p&amp;lt;0.0001NP, at baseline and follow-up, respectively]. Likewise, the average CAC density was higher at follow-up [CAC density: 228.8±35.4 vs. 232.6±37.0; p&amp;lt;0.0001]. HIST vs. LIST more effectively reduced LDL-cholesterol (annualized change: −58.6±50.9 vs. −44.4±43.7 mg/dL, p=0.005). Comparing patients on HIST vs. LIST, CAC density at follow-up (231.9±36.1 HU vs. 233.3±37.7, p=0.59) and its change from baseline (4.0±19.1 HU vs. 3.6±19.6 HU, p=0.73) did not differ. Subgroup analyses, stratifying by LDL-reduction ( Conclusion HIST vs. LIST leads to a higher reduction in cholesterol levels, which does not translate into relevant differences in the change of CAC density at one-year follow-up. Funding Acknowledgement Type of funding sources: None.

Brussels Chicory Stabilizes Unstable Atherosclerotic Plaques and Reshapes the Gut Microbiota in Apoe−/− Mice

Adherence to a Mediterranean dietary pattern can protect against atherosclerosis in part by reducing intestinal permeability and gut microbial LPS production. Brussels chicory, a typical Mediterranean vegetable, has been shown to inhibit the formation of early-stage atherosclerosis in mice. We evaluated whether Brussels chicory affects advanced atherosclerosis progression, intestinal permeability, and gut microbial LPS production. Thirty-week-old male apoE-deficient mice with unstable atherosclerotic plaques in the brachiocephalicarterywere fed the AIN-93G diet alone (control) or supplemented with 0.5% freeze-dried Brussels chicory for 20 wk. Plaque volume and features of plaque stability, plaque macrophage polarization, fecal and serum LPS concentrations, serum lipid profiles and inflammation-related cytokines, and gut microbial profiles were measured. Compared with the control treatment, Brussels chicory consumption did not significantly change plaque volume and serum lipid profiles. However, it increased plaque stability (P < 0.05), as evidenced by reduced necrotic core size (42.3%), and increased fibrous cap thickness (55.0%) and collagen content (68.4%). Moreover, Brussels chicory consumption reduced intestinal permeability (56.3%), fecal and serum LPS concentrations (52.2% and 39.4%), serum IL1β and TNFα (52.0% and 33.8%), promoted plaquemacrophage polarization towards the M2-likephenotype, and altered gut microbial composition, the latter indicated by increased relative abundance of certain members of the Ruminococcaceae family, such as Ruminiclostridium_9, Ruminiclostridium_5, and Intestinimonas (P < 0.05). Spearman correlation analyses further showed that these bacterial genera were significantly correlated with intestinal permeability, fecal and serum LPS, serum proinflammatory cytokines, and several features of plaque stability. Brussels chicory might help stabilize atherosclerotic plaques in mice by reducing intestinal permeability and gut microbial LPS production. This study provides a promising approach to slow the progression of atherosclerosis.

Effect of B-mode ultrasound- guided extracorporeal low- level focused sonotherapy on early stage atherosclerosis regression using color doppler ultrasonography and histopathology

Background and Aims : Excessive lipid accumulation by macrophages plays a crucial role in atherosclerosis. Foam cells are generated by uncontrolled uptake of modified LDL, especially oxidized LDL. We developed an experimental sonotherapy system and investigated its effectiveness on macrophage- derived foam cells density reduction and arterial hemodynamic parameters improvement, wherein diagnostic B- mode ultrasound is combined with the therapy system, with a goal of increased safety.Methods: Briefly, New Zealand white rabbits underwent primary balloon dilatation injury at the right common carotid artery followed by a 1.5% cholesterol-rich diet injury for three weeks. Histopathology and B- mode ultrasonography results showed the early stage atherosclerosis formation in all of the rabbits' arteries. Then, treatment group underwent extracorporeal low- level focused sonotherapy (F= 1 MHz, I= 2 w/cm2, PD= 100 ms). Foam cells density and arterial hemodynamic parameters were evaluated in the treatment group compared with the control group using histopathology and color Doppler ultrasonography, respectively.Results: from histopathology and color Doppler ultrasonography showed a significant reduction in the mean value for immune and foam cells density, Resistive Index (RI), Pulsatility Index (PI), Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV), Mean Velocity (MV) and significant increase in the mean value for volume Flow (VF) in the treatment group compared with the control group (p < 0.05).Conclusions: Anti- inflammatory, lipid effluxion, reverse cholesterol transport and machrophages egress effect of sonotherapy reduces the immune and foam cells density and increase the endothelial Nitric Oxide synthase (eNOS), resulting in arterial hemodynamic parameters improvement and early stage atherosclerosis regression. Background and Aims : Excessive lipid accumulation by macrophages plays a crucial role in atherosclerosis. Foam cells are generated by uncontrolled uptake of modified LDL, especially oxidized LDL. We developed an experimental sonotherapy system and investigated its effectiveness on macrophage- derived foam cells density reduction and arterial hemodynamic parameters improvement, wherein diagnostic B- mode ultrasound is combined with the therapy system, with a goal of increased safety. Methods: Briefly, New Zealand white rabbits underwent primary balloon dilatation injury at the right common carotid artery followed by a 1.5% cholesterol-rich diet injury for three weeks. Histopathology and B- mode ultrasonography results showed the early stage atherosclerosis formation in all of the rabbits' arteries. Then, treatment group underwent extracorporeal low- level focused sonotherapy (F= 1 MHz, I= 2 w/cm2, PD= 100 ms). Foam cells density and arterial hemodynamic parameters were evaluated in the treatment group compared with the control group using histopathology and color Doppler ultrasonography, respectively. Results: from histopathology and color Doppler ultrasonography showed a significant reduction in the mean value for immune and foam cells density, Resistive Index (RI), Pulsatility Index (PI), Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV), Mean Velocity (MV) and significant increase in the mean value for volume Flow (VF) in the treatment group compared with the control group (p < 0.05). Conclusions: Anti- inflammatory, lipid effluxion, reverse cholesterol transport and machrophages egress effect of sonotherapy reduces the immune and foam cells density and increase the endothelial Nitric Oxide synthase (eNOS), resulting in arterial hemodynamic parameters improvement and early stage atherosclerosis regression.

Early stage atherosclerosis regression, using b- mode ultrasound- guided chlor- aluminium sulfonated phthalocyanine - mediated catheter- based low level red laser photodynamic therapy

Background and Aims : Excessive lipid accumulation by macrophages plays a crucial role in atherosclerosis. Foam cells are generated by uncontrolled uptake of modified LDL, especially oxidized LDL (oxLDL). Photodynamic therapy is a treatment that uses photosensitizing agents, along with light to kill cancerous and hyperplasia cells.The aim of this study was to evaluate the effect of chlor- aluminium sulfonated phthalocyanine (CASPc)- mediated photodynamic therapy on early stage atherosclerotic regression, wherein diagnostic B- mode ultrasound is combined with laser system, with a goal of increased safety.

Sinoporphyrin sodium (DVDMS)- loaded nanoliposomes- mediated B-mode ultrasound- guided sono- photodynamic combination therapy of early stage atherosclerosis

Background and Aims : Excessive lipid accumulation by macrophages plays a crucial role in atherosclerosis. Sinoporphyrin sodium (DVDMS) is a novel sensitizer and widely used in photodynamic and sonodynamic therapy. We developed an experimental sono- photodynamic combination therapy system and investigated its effectiveness on macrophages- derived foam cells density (inflammation) reduction.

Isobavachalcone attenuates TNF-α-induced ICAM-1 and VCAM-1 expression in human umbilical vein endothelial cells by regulating the NF-κB signaling pathway

Vascular inflammation activated by pro-inflammatory cytokines is an inflammatory response that occurs in the early stages of atherosclerosis. Endothelial dysfunction in vascular inflammation begins with the expression of cell surface adhesion molecules by pro-inflammatory cytokines. The purpose of this study was to evaluate and verify the vascular inflammatory effects of isobavachalcone. In this study, we investigated the effects of isobavachalcone on inflammatory responses in vascular inflammation induced by the tumor necrosis factor-α (TNF-α) in human umbilical vein endothelial cells (HUVECs). TNF-α stimulation significantly increased the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) proteins, and concentration-dependently decreased by isobavachalcone in HUVECs. Isobavachalcone suppressed TNF-α-induced ICAM-1 and VCAM-1 expression in HUVECs, thereby inhibiting TNF-α-induced increase in monocyte adhesion. In addition, isobavachalcone decreased the phosphorylation of the NF-κB (necrosis factor κB) p65 subunit. The findings of this study demonstrate that isobavachalcone prevents TNF-α-induced vascular inflammation and has the potential to protect against the early progression of atherosclerosis.