Effective Treatment Of Atherosclerosis Research Articles

Mild phototherapy mediated by IR780-Gd-OPN nanomicelles suppresses atherosclerotic plaque progression through the activation of the HSP27-regulated NF-κB pathway

Reducing plaque lipid content and enhancing plaque stability without causing extensive apoptosis of foam cells are ideal requirements for developing a safe and effective treatment of atherosclerosis. In this study, we synthesized IR780-Gd-OPN nanomicelles by conjugating osteopontin (OPN) and loading a gadolinium-macrocyclic ligand (Gd-DOTA) onto near-infrared dye IR780-polyethylene glycol polymer. The nanomicelles were employed for mild phototherapy of atherosclerotic plaques and dual-mode imaging with near-infrared fluorescence and magnetic resonance. In vitro results reveal that the mild phototherapy mediated by IR780-Gd-OPN nanomicelles not only activates heat shock protein (HSP) 27 to protect foam cells against apoptosis but also inhibits the nuclear factor kappa-B (NF-κB) pathway to regulate lipid metabolism and macrophage polarization, thereby diminishing the inflammatory response. In vivo results further validate that mild phototherapy effectively reduces plaque lipid content and size while simultaneously enhancing plaque stability by regulating the ratio of M1 and M2-type macrophages. In summary, this study presents a promising approach for developing a safe and highly efficient method for the precise therapeutic visualization of atherosclerosis. Statement of significanceThe rupture of unstable atherosclerotic plaques is a major cause of high mortality rates in cardiovascular diseases. Therefore, the ideal outcome of atherosclerosis treatment is to reduce plaque size while enhancing plaque stability. To address this challenge, we designed IR780-Gd-OPN nanomicelles for mild phototherapy of atherosclerosis. This treatment can effectively reduce plaque size while significantly improving plaque stability by increasing collagen fiber content and elevating the ratio of M2/M1 macrophages, which is mainly attributed to the inhibition of the NF-κB signaling pathway by mild phototherapy-activated HSP27. In summary, our proposed mild phototherapy strategy provides a promising approach for safe and effective treatment of atherosclerosis.

Integration of 16S rRNA sequencing and metabolomics to investigate the modulatory effect of ginsenoside Rb1 on atherosclerosis

Background/aims: Atherosclerosis (AS) is the common pathological basis of a variety of cardiovascular diseases (CVD), and has become the main cause of human death worldwide, and the incidence is increasing and younger trend. Ginsenoside Rb1 (Rb1), an important monomer component of the traditional Chinese herb ginseng, known for its ability to improve blood lipid disorders and anti-inflammatory. In addition, Rb1 was proved to be an effective treatment for AS. However, the effect of Rb1 on AS remains to be elucidated. The aim of this study was to investigate the mechanisms of Rb1 in ameliorating AS induced by high-fat diet (HFD). Materials and methodsIn this study, we developed an experimental AS model in Sprague-Dawley rats by feeding HFD with intraperitoneal injection of vitamin D3. The potential therapeutic mechanism of Rb1 in AS rats was investigated by detecting the expression of inflammatory factors, microbiome 16S rRNA gene sequencing, short-chain fatty acids (SCFAs) targeted metabolomics and untargeted metabolomics. ResultsRb1 could effectively alleviate the symptoms of AS and suppress the overexpression of inflammation-related factors. Meanwhile, Rb1 altered gut microbial composition and concentration of SCFAs characterized by Bacteroidetes, Actinobacteria, Lactobacillus, Prevotella, Oscillospira enrichment and Desulfovibrio depletion, accompanied by increased production of acetic acid and propionic acid. Moreover, untargeted metabolomics showed that Rb1 considerably improved faecal metabolite profiles, particularly arachidonic acid metabolism and primary bile acid biosynthesis. ConclusionRb1 ameliorated the HFD-induced AS, and the mechanism is related to improving intestinal metabolic homeostasis and inhibiting systemic inflammation by regulating gut microbiota.

Scavenger receptor-targeted plaque delivery of microRNA-coated nanoparticles for alleviating atherosclerosis

Atherosclerosis treatments by gene regulation are garnering attention, yet delivery of gene cargoes to atherosclerotic plaques remains inefficient. Here, we demonstrate that assembly of therapeutic oligonucleotides into a three-dimensional spherical nucleic acid nanostructure improves their systemic delivery to the plaque and the treatment of atherosclerosis. This noncationic nanoparticle contains a shell of microRNA-146a oligonucleotides, which regulate the NF-κB pathway, for achieving transfection-free cellular entry. Upon an intravenous injection into apolipoprotein E knockout mice fed with a high-cholesterol diet, this nanoparticle naturally targets class A scavenger receptor on plaque macrophages and endothelial cells, contributing to elevated delivery to the plaques (∼1.2% of the injected dose). Repeated injections of the nanoparticle modulate genes related to immune response and vascular inflammation, leading to reduced and stabilized plaques but without inducing severe toxicity. Our nanoparticle offers a safe and effective treatment of atherosclerosis and reveals the promise of nucleic acid nanotechnology for cardiovascular disease.

Atherosclerosis in HIV Patients: What Do We Know so Far?

For the past several decades, humanity has been dealing with HIV. This disease is one of the biggest global health problems. Fortunately, modern antiretroviral therapy allows patients to manage the disease, improving their quality of life and their life expectancy. In addition, the use of these drugs makes it possible to reduce the risk of transmission of the virus to almost zero. Atherosclerosis is another serious pathology that leads to severe health problems, including disability and, often, the death of the patient. An effective treatment for atherosclerosis has not yet been developed. Both types of immune response, innate and adaptive, are important components of the pathogenesis of this disease. In this regard, the peculiarities of the development of atherosclerosis in HIV carriers are of particular scientific interest. In this review, we have tried to summarize the data on atherosclerosis and its development in HIV carriers. We also looked at the classic therapeutic methods and their features concerning the concomitant diagnosis.

Research Progress of Atherosclerosis-Related Youth Stroke

In recent years, the incidence of ischemic stroke has shown a trend of younger people, which has caused serious harm to young people’s daily life and physical health. Therefore, youth ischemic stroke has also received more and more attention from the medical community. Atherosclerotic stroke is the main cause of stroke in young stroke patients. Therefore, early prevention, early diagnosis, early intervention and effective treatment of atherosclerosis are particularly important. In this paper, by reviewing domestic and foreign literature, a systematic overview of the risk factors of atherosclerotic stroke was carried out, and new ideas for atherosclerotic stroke were provided.

Black TiO2 nanoprobe-mediated mild phototherapy reduces intracellular lipid levels in atherosclerotic foam cells via cholesterol regulation pathways instead of apoptosis

Given that apoptosis increases the risk of plaque rupture, strategies that reduce intracellular lipid levels without killing foam cells are warranted for safe and effective treatment of atherosclerosis. In this study, a mild phototherapy strategy is carried out to achieve the hypothesis. Foam cell-targeted nanoprobes that allow photothermal therapy (PTT) and/or photodynamic therapy (PDT) were prepared by loading hyaluronan and porphine onto black TiO2 nanoparticles. The results showed that when temperatures below 45 °C, PTT alone and PTT + PDT significantly reduced the intracellular lipid burden without inducing evidently apoptosis or necrosis. In contrast, the use of PDT alone resulted in only a slight reduction in lipid levels and induced massive apoptosis or necrosis. The protective effect against apoptosis or necrosis after mild-temperature PTT and PTT + PDT was correlated with the upregulation of heat shock protein 27. Further, mild-temperature PTT and PTT + PDT attenuated intracellular cholesterol biosynthesis and excess cholesterol uptake via the SREBP2/LDLR pathway, and also triggered ABCA1-mediated cholesterol efflux, ultimately inhibiting lipid accumulation in foam cells. Our results offer new insights into the mechanism of lipid regulation in foam cells and indicate that the black TiO2 nanoprobes could allow safer and more effective phototherapy of atherosclerosis.

ROS-Based Nanoparticles for Atherosclerosis Treatment.

Atherosclerosis (AS), a chronic arterial disease, is the leading cause of death in western developed countries. Considering its long-term asymptomatic progression and serious complications, the early prevention and effective treatment of AS are particularly important. The unique characteristics of nanoparticles (NPs) make them attractive in novel therapeutic and diagnostic applications, providing new options for the treatment of AS. With the assistance of reactive oxygen species (ROS)-based NPs, drugs can reach specific lesion areas, prolong the therapeutic effect, achieve targeted controlled release and reduce adverse side effects. In this article, we reviewed the mechanism of AS and the generation and removal strategy of ROS. We further discussed ROS-based NPs, and summarized their biomedical applications in scavenger and drug delivery. Furthermore, we highlighted the recent advances, challenges and future perspectives of ROS-based NPs for treating AS.

Targeting and deep-penetrating delivery strategy for stented coronary artery by magnetic guidance and ultrasound stimulation.

Stent placement is an effective treatment for atherosclerosis, but is suffered from in-stent restenosis (ISR) caused by stent mechanical damage. Conventional ISR treatment such as drug-eluting stents (DES) is challenged by the low therapeutic efficacy and severe complications, unchangeable drug dosage for individuals, and limited drug penetration in the vascular tissue. We hypothesize that magnetic targeting and deep-penetrating delivery strategy by magnetic guidance and ultrasound stimulation might be an effective approach for ISR treatment. In the present study, antiproliferative drug (paclitaxel, PTX) loaded poly (lactide-co-glycolide) (PLGA) nanoparticles (PLGA-PTX) were embedded within the shells of the magnetic nanoparticle coated microbubbles (MMB-PLGA-PTX). Once being targeted to the stent under a magnetic field, a low intensity focused ultrasound (LIFU) is applied to activate stable microbubble oscillations, thereby triggering the release of PLGA-PTX. The generated mechanical force and microstreaming facilitate the penetration of released PLGA-PTX into the thickened vascular tissue and enhance their internalization by smooth muscle cells (SMCs), thereby reducing the clearance by blood flow. In an ex vivo experiment, magnetic targeting improved the accumulation amount of MMB-PLGA-PTX by 10 folds, while the LIFU facilitated the penetration of released PLGA-PTX into the tunica media region of the porcine coronary artery, resulting in prolonged retention time at the stented vascular tissue. With the combination effects, this strategy holds great promise in the precision delivery of antiproliferative drugs to the stented vascular tissue for ISR treatment.

Percutaneous enzyme emulsification endarterectomy

HYPOTHESIS Open endarterectomy is an effective treatment for atherosclerosis,1 and, Percutaneous endovascular techniques are associated with faster recovery and reduced complication rates,2 and An atherosclerotic plaque is made up of broadly the same components across the population,3 so Endovascular application of an enzyme/emulsifier mixture to an isolated vessel will allow the degradation, emulsification and removal of the atherosclerotic plaque and intima. VASCULAR SURGICAL APPROACHES to atherosclerotic vessels involve physical methods to treat atherosclerotic arteries vary between the use of stents or balloons to endarterectomy or bypass. Open-vessel endarterectomy has been established as an effective technique for the surgical management of arteries severely stenosed by atherosclerosis.1 However, endarterectomy requires open dissection, and its success depends on the skill of the operator. Furthermore, this technique usually is feasible only for short lengths of affected arteries. If a percutaneous technique could be developed, it would allow for endarterectomy to be performed with less dissection, leading to decreased operating times, decreased operative trauma, and faster recovery rates.

Metabonomics Study of TCM Formula: Qutan Huayu Tongmai Granule as an Effective Treatment for Atherosclerosis in Mini-Pigs

To investigate the effects of QuTan HuaYu TongMai granule (QHTG) on the perturbed metabolism of atherosclerosis mini-pig model, a serum metabonomics method based on Liquid chromatography/mass spectrometry was developed. Principal component analysis and partial least squares-discriminate analysis models were established for the metabonomics analysis. The effect of high dose QHTG group is equivalent with those of positive drugs group in PCA score plots. Some significantly changed metabolites, including lyso-PCs, metabolites of vitamin D3 and fatty acids were found to be reasonable in explaining the anti-atherosclerosis mechanism of QHTG. Metabonomic approach is helpful to further understand the pathophysiology of atherosclerosis in mini-pigs and the therapeutic mechanism of QHTG. Our work also indicated that the LC–MS based metabonomics method is a potential tool for performing intervention and mechanism research of traditional Chinese medicine (TCM).

Inhibition of TLR4 signaling pathway: Molecular treatment strategy of periodontitis-associated atherosclerosis

The accumulation of epidemiologic, pathologic, and animal model studies suggests that periodontal infection may be a contributing risk factor for atherosclerosis. The Toll-like receptor-4 (TLR4) signaling pathway plays an important role in the initiation and progression of periodontitis-associated atherosclerotic disease. We postulate that suppression of TLR4 signaling pathway can be an effective treatment for atherosclerosis. These strategies include prevention of ligand binding to TLR4, blocking the interactions of TLR4s and adaptors in signaling pathways, blocking the enzymes in signaling pathways, and immunostimulation with vaccine adjuvants. However, we should be aware that there may be unknown risks about the new technologies and these drugs, which may cause some unknown side effects in long-term administration.

The significance of detection of preclinical atherosclerosis

Background: Atherosclerosis is a chronic disease, which can go on for many decades with no clinically noticable changes. When clinical symptoms appear, the disease has usually already significantly progressed. There is currently no effective treatment for atherosclerosis. The disease can only be prevented. This is why it is important to detect it in its early stages, when preventive measures are the most effective. Today, with a help of non-invasive investigation methods, mostly ultrasound based, we can detect changes in the structure and function of artery wall, which are typical for the early stages of atherosclerosis or predict the disease course. Conclusions: Such changes are: lower capability of artery expansion during an increased blood flow (endothelial dysfunction), intima-media thickening, artery walls, artery calcination and ankle-brachial index decrease. The research showed that these symptoms of preclinical atherosclerosis are tightly connected to authenticity of the risk factors, their number and duration, and that there is a tight connection between the general cardiovascular danger and the manifestation of preclinical and morphological changes of an artery wall. Preclinical atherosclerotic changes are very important signals of cardiovascular changes and are independent of classical atherosclerotic risk factors. Contrary to the current means of evaluating risks (see tables) that enable us to evaluate statistical values concerning risks for the population based on present risk factors, assessing the preclinical forms of atherosclerosis enables us to recognize those individuals who are at greatest risk, i.e. those where a process of atherosclerosis has already begun and who need immediate elimination of the risk factors. In this way, the finding of a disturbance in the vein wall (endothelial dysfunction) or its structure (intima-media thickening) can help choose the right preventive measure, meaning that in patients, where the general risk is, according to classical risk factors, which were established to be low or medium, suggesting the usage of intensive preventive measures, including the usage of drugs, used for treating current risk factors, even though there is a borderline or a minor increase of their values.

Th-P16:406 Effective treatment of atherosclerosis by dosage optimization of atorvastatin

Th-P16:406 Effective treatment of atherosclerosis by dosage optimization of atorvastatin

Combining β-adrenergic and peroxisome proliferator–activated receptor γ stimulation improves lipoprotein composition in healthy moderately obese subjects

Current pharmacological regimens for hypertriglyceridemia and low high-density lipoprotein (HDL) are limited to the peroxisome proliferator–activated receptor (PPAR) α activating fibrates, niacin, and statins. This pilot study examined the impact of simultaneous stimulation of cyclic adenosine monophosphate with a β-adrenergic agonist and PPAR γ with pioglitazone (PIO) on lipoprotein composition in moderately obese, healthy subjects. Subjects were treated with PIO (45 mg) to stimulate PPAR γ or a combination of ephedrine (25 mg TID), a β-agonist, with caffeine (200 mg TID), a phosphodiesterase inhibitor (ephedrine plus caffeine), or both for 16 weeks. Lipoproteins were separated by gradient ultracentrifugation into very low-density lipoprotein (VLDL), intermediate-density lipoprotein, low-density lipoprotein (LDL), and 3 HDL (L, M, and D) subfractions. Apolipoproteins were measured by high-performance liquid chromatography. PIO alone reduced the core triglyceride (TG) content relative to cholesterol ester (CE) in VLDL (−40%), IDL (−25%), and HDL-M (−38%). Ephedrine plus caffeine alone reduced LDL CE (−13%), phospholipids (−9%), and apolipoprotein (apo) B (−13%); increased HDL-M LpA-I (HDL containing apoA-I without apoA-II, 28%), CE/TG (23%), and CE/apoA-I (8%) while reducing apoA-II (−10%); and increased HDL-L LpA-I (29%). Combination therapy reduced total plasma TG (−28%), LDL cholesterol (LDL-C, −10%), apoB (−16%), apoB/apoA-I ratio (−21%) while increasing HDL cholesterol (HDL-C, 21%), total plasma apoA-I (12%), LpA-I (43%), and apoC-I (26%). It also reduced VLDL total mass (−34%) and apoC-III (−39%), LDL CE (−13%), apoB (−13%), and total mass (−11%). Combination therapy increased HDL-L CE/TG (32%), apoC-I (30%), apoA-I (56%), and LpA-I (70%), as well as HDL-M CE (35%), phospholipids (24%), total mass (19%), apoC-I (25%), apoA-I (18%), and LpA-I (56%). In conclusion, simultaneous β-adrenergic and PPAR γ activation produced beneficial effects on VLDL, LDL, HDL-L, and HDL-M. Perhaps the most important impact of combination therapy was dramatic increases in LpA-I and apoC-I in HDL-L and HDL-M, which were much greater than the sum of the monotherapies. Because LpA-I appears to be the most efficient mediator of reverse-cholesterol transport and a major negative risk factor for cardiovascular disease, this combination therapy may provide very effective treatment of atherosclerosis.

Antiatherogenic Effects of <i>Phyllanthus Emblica</i> Associated with Corilagin and its Analogue

Oxidized low-density lipoprotein (ox-LDL) is the main etiologic factor in atherogenesis, and antioxidants are accepted as effective treatment of atherosclerosis. The aim of this study was to clarify whether the mechanism of the antiatherogenic effects of the herb Phyllanthus Emblica, which is widely used to treat atherosclerosis-related diseases, is associated with ox-LDL via its compounds of soluble tannin, corilagin (beta-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), and its analogue Dgg16 (1,6-di-O-galloyl-beta-d-glucose). Human umbilical vein endothelial cells, ECV-304, were incubated with ox-LDL (50 mg/l), treated with corilagin or Dgg16 at different doses (0.0001-0.1 mmol/l), and then incubated with monocytes. Malondialdehyde (MDA) in the culture media was determined and the number of monocytes adhering to ECV-304 cells was counted with cytometry. In another experiment, the rat vascular smooth muscular cells (VSMC) were incubated in media with or without ox-LDL (50 mg/l), and with corilagin or Dgg16 also at different doses (0.0001-0.1 mol/l), the proliferation of which was assayed with MTT. The results showed that both corilagin and Dgg16 were able to decrease MDA, prevented ECV-304 cells from being adhering to by monocytes, and inhibited VSMC proliferation activated by ox-LDL. The results suggest that the two compounds are effective in inhibiting the progress of atherosclerosis by alleviating oxidation injury or by inhibiting ox-LDL-induced VSMC proliferation, which may be promising mechanisms for treating atherosclerosis.