Rapid inhibition of atherosclerotic plaque progression by sonodynamic therapy

2018 ◽  
Vol 115 (1) ◽  
pp. 190-203 ◽  
Author(s):  
Xin Sun ◽  
Shuyuan Guo ◽  
Jianting Yao ◽  
Huan Wang ◽  
Chenghai Peng ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Standard Of Care ◽  
Atherosclerotic Plaques ◽  
Plaque Progression ◽  
Peripheral Artery ◽  
Sonodynamic Therapy ◽  
Non Invasive ◽  
Atherosclerotic Burden ◽  
Artery Disease ◽  
Apoe Deficient Mouse

Abstract Aims Currently, efficient regimens to reverse atherosclerotic plaques are not available in the clinic. Herein, we present sonodynamic therapy (SDT) as a novel methodology to rapidly inhibit progression of atherosclerotic plaques. Methods and results In atherosclerotic rabbit and apoE-deficient mouse models, SDT efficiently decreased the atherosclerotic burden within 1 week, revealing a decrease in the size of the atherosclerotic plaque and enlarged lumen. The shrunken atherosclerotic plaques displayed compositional alterations, with a reduction in lesional macrophages and lipids. The rapid efficacy of SDT may be due to its induction of macrophage apoptosis, enhancement of efferocytosis, and amelioration of inflammation in the atherosclerotic plaque. Compared with atorvastatin, the standard of care for atherosclerosis, SDT showed more significant plaque shrinkage and lumen enlargement during 1 week treatment. Furthermore, SDT displayed good safety without obvious side effects. In a pilot clinical trial recruiting the patients suffering atherosclerotic peripheral artery disease, combination therapy of SDT with atorvastatin efficiently reduced progression of atherosclerotic plaque within 4 weeks, and its efficacy was able to last for at least 40 weeks. Conclusion SDT is a non-invasive and efficacious regimen to inhibit atherosclerotic plaque progression.

scholarly journals Non-Lethal Sonodynamic Therapy Inhibits Atherosclerotic Plaque Progression in ApoE-/- Mice and Attenuates ox-LDL-mediated Macrophage Impairment by Inducing Heme Oxygenase-1

2017 ◽  
Vol 41 (6) ◽  
pp. 2432-2446 ◽  
Author(s):  
Yu Wang ◽  
Wei Wang ◽  
Haobo Xu ◽  
Yan Sun ◽  
Jing Sun ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Western Blotting ◽  
Heme Oxygenase ◽  
Atherosclerotic Plaque ◽  
Heme Oxygenase 1 ◽  
Atherosclerotic Plaques ◽  
Protective Effects ◽  
Plaque Progression ◽  
Sonodynamic Therapy ◽  
Low Intensity

Background: Previous studies from our group showed that low-intensity sonodynamic therapy (SDT) has protective effects on atherosclerosis (AS). However, because the intensity of ultrasound passing through tissue is attenuated, the consequences of very low-intensity SDT, referred to as non-lethal SDT (NL-SDT), on atherosclerotic plaques are unclear. The aim of this study was to determine whether NL-SDT affects atherosclerotic plaques and to elucidate the possible underlying mechanisms. Methods: An AS model was established using ApoE-/- mice fed a western diet. En face Oil Red O staining was used to measure atherosclerotic plaque size. Hematoxylin and eosin staining and immunohistochemical staining were used to observe plaque morphology and assess the location of macrophages and heme oxygenase 1 (HO-1). HO-1 mRNA and protein levels in AS plaques were evaluated by real-time PCR and western blotting. Human THP-1 cells and mouse peritoneal macrophages were used in this study. Western blotting was used to investigate the expression of cellular proteins after NL-SDT. Macrophage apoptosis was evaluated by TUNEL assays and flow cytometry with Annexin V/PI double staining. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were measured with 2′-7′-dichlorofluorescein diacetate (DCFH-DA) and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl benzimidazolyl carbocyanine iodide (JC-1) staining, respectively. Results: NL-SDT significantly inhibited AS progression and reduced the necrotic core area. NL-SDT induced HO-1 expression in lesional macrophages and in cultured macrophages. NL-SDT activated the protein kinase B (AKT) and extracellular signal-related protein kinase (ERK) pathways and the transcription factor NF-E2-related factor 2 (Nrf2).NL-SDT significantly reduced oxidized LDL (ox-LDL)-induced macrophage MMP collapse, ROS production and cell apoptosis. Zinc protoporphyrin (ZnPP), a HO-1-specific inhibitor, reversed the protective effects of NL-SDT. Conclusion: NL-SDT inhibits atherosclerotic plaque progression and increases plaque stability. In vitro, NL-SDT has a protective effect on ox-LDL-induced macrophage impairment via HO-1.

Abstract 11: Effects of Canakinumab in Patients With Peripheral Artery Disease

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Kerry S Russell ◽  
Denise Yates ◽  
Andrea Feller ◽  
Tianke Wang ◽  
Ping Chen ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Vascular Function ◽  
Cardiovascular Events ◽  
Ankle Brachial Index ◽  
Unmet Need ◽  
Walking Distance ◽  
Plaque Progression ◽  
Peripheral Artery ◽  
Plaque Volume ◽  
Artery Disease

Background: Peripheral artery disease (PAD) affects 8.5 million people in the US. PAD patients are at high risk for cardiovascular events, and their quality of life is often significantly impaired by decreased mobility. Interleukin-1β (IL-1β) may play an important role in this disease by promoting inflammatory responses that drive atherosclerotic plaque progression and impair vascular function. We sought to test whether interruption of IL-1β signaling would improve patient mobility and decrease plaque progression in the lower extremities. Methods: 38 patients (mean age 65; 71% male) with symptomatic PAD (confirmed by ankle-brachial index) were randomized 1:1 to receive Canakinumab (150 mg subcutaneously) or placebo monthly for up to 12 months. Plaque volume in the superficial femoral artery (SFA) was assessed serially using 3.0T MRI. Mobility was assessed serially using the 6-minute walk test (maximum and pain-free walking distance). Results: Canakinumab was safe and well-tolerated. 12 patients discontinued (8 placebo, 4 Canakinumab). MRI data (from 31 patients at 3 months; 21 patients at 12 months) showed no evidence of plaque progression in the SFA at either time point in placebo-treated patients; nor was there a change in plaque volume in the Canakinumab-treated group. There was a serial and significant improvement in placebo-adjusted maximum and pain-free walking distance observed as early as 3 months after treatment with Canakinumab (58-meter improvement over placebo in pain-free distance at 3 months, P=0.01). Two placebo-treated patients required peripheral vascular interventions due to progression of disease; however, no Canakinumab-treated patients required revascularization during the study. Canakinumab decreased markers of systemic inflammation (IL-6 and hsCRP). Conclusions: Treatment with Canakinumab may improve maximum and pain-free walk distance in patients with symptomatic PAD. In conjunction with results soon to be reported for the CANTOS trial of Canakinumab for secondary prevention of cardiovascular events, additional studies may provide support that inhibition of IL-1β signaling can improve symptoms and function in this patient population with high unmet need.

Non-invasive evaluation of extracellular matrix remodeling in peripheral artery disease

2017 ◽  
Vol 263 ◽  
pp. e68
Author(s):  
Anna Hernández Aguilera ◽  
Signe H. Nielsen ◽  
Salvador Fernández-Arroyo ◽  
Vicente Martín-Paredero ◽  
Morten A. Karsdal ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Peripheral Artery Disease ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Peripheral Artery ◽  
Non Invasive ◽  
Artery Disease ◽  
Invasive Evaluation

PET-CT and detection of coronary artery disease

2021 ◽  
pp. 421-434
Author(s):  
Marcelo F. Di Carli
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Microvascular Dysfunction ◽  
Quantitative Information ◽  
Left Ventricular ◽  
Coronary Microvascular Dysfunction ◽  
Non Invasive ◽  
Atherosclerotic Burden ◽  
Pet Ct ◽  
Artery Disease

Myocardial perfusion PET/CT imaging has emerged as a powerful and comprehensive non-invasive approach for the management of patients with suspected or known coronary artery disease (CAD). The multiparametric PET/CT approach provides quantitative information about the extent and severity of focal and diffuse CAD, coronary microvascular dysfunction (CMD), atherosclerotic burden, and left ventricular function. Contemporary evidence demonstrates that this comprehensive approach is one of the most accurate non-invasive tools for diagnosis, risk prediction, and guiding management in patients with CAD. This chapter summarizes the versatility of the integrated PET/CT scan to provide detailed quantitative information tailored to the patient and clinical question. I then review patient-centred clinical applications using case vignettes to illustrate indications of PET/CT and how to present the findings into clinically actionable information for the practising cardiologist. In each case, I review the available data highlighting the diagnostic and prognostic value of the integrated PET/CT protocol.

scholarly journals PEMERIKSAAN FUNGSI ENDOTEL PADA PENYAKIT KARDIOVASKULAR

2020 ◽  
Vol 5 (3) ◽  
pp. 638
Author(s):  
Adhi Kurniawan ◽  
Mefri Yanni
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Endothelial Dysfunction ◽  
Early Stage ◽  
Endothelial Damage ◽  
Vascular Endothelial ◽  
Peripheral Artery ◽  
Non Invasive ◽  
Artery Disease ◽  
Initial Process

<p>Cardiovascular risk factors have been known to play a role in vascular endothelial damage. Endothelial damage can cause a condition called endothelial dysfunction. Endothelial dysfunction  is the initial process of various cardiovascular problems such as coronary heart disease, stroke, peripheral artery disease, and  others. Early stage endothelial damage can actually be detected, but often patients present at the stage of cardiovascular problems. Various examinations of endothelial function start from invasive, non invasive, until biomarkers marking the occurrence of dysfunction can be done. So that we can prevent or reduce the occurrence of further damage</p>

scholarly journals Increased miR-142 Levels in Plasma and Atherosclerotic Plaques from Peripheral Artery Disease Patients with Post-Surgery Cardiovascular Events

2020 ◽  
Vol 21 (24) ◽  
pp. 9600
Author(s):  
Teodora Barbalata ◽  
Oriana E. Moraru ◽  
Camelia S. Stancu ◽  
Yvan Devaux ◽  
Maya Simionescu ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Plasma Levels ◽  
Cardiovascular Events ◽  
Plasma Lipids ◽  
Artery Bypass ◽  
Atherosclerotic Plaques ◽  
Peripheral Artery ◽  
Disease Evolution ◽  
Post Surgery ◽  
Artery Disease

There is an intensive effort to identify biomarkers to predict cardiovascular disease evolution. We aimed to determine the potential of microRNAs to predict the appearance of cardiovascular events (CVEs) in patients with peripheral artery disease (PAD) following femoral artery bypass surgery. Forty-seven PAD patients were enrolled and divided into two groups, without CVEs (n = 35) and with CVEs (n = 12), during 1 year follow-up. Intra-surgery atherosclerotic plaques from femoral arteries were collected and the levels of miR-142, miR-223, miR-155, and miR-92a of the primary transcripts of these microRNAs (pri-miRNAs), and gene expression of Drosha and Dicer were determined. Results showed that, in the plaques, miR-142, miR-223, and miR-155 expression levels were significantly increased in PAD patients with CVEs compared to those without CVEs. Positive correlations between these miRNAs and their pri-miRNAs levels and the Dicer/Drosha expression were observed. In the plasma of PAD patients with CVEs compared to those without CVEs, miR-223 and miR-142 were significantly increased. The multiple linear regression analyses revealed significant associations among several plasma lipids, oxidative and inflammatory parameters, and plasma miRNAs levels. Receiver operator characteristic (ROC) analysis disclosed that plasma miR-142 levels could be an independent predictor for CVEs in PAD patients. Functional bioinformatics analyses supported the role of these miRNAs in the regulation of biological processes associated with atherosclerosis. Taken together, these data suggest that plasma levels of miR-142, miR-223, miR-155, and miR-92a can significantly predict CVEs among PAD patients with good accuracy, and that plasma levels of miR-142 can be an independent biomarker to predict post-surgery CVEs development in PAD patients.

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