Atheromatous Plaque Formation Research Articles

Impact of hypertension and arterial wall expansion on transport properties and atherosclerosis progression

This study explored the impact of hypertension on atheroma plaque formation through a mechanobiological model. The model incorporates blood flow via the Navier–Stokes equation. Plasma flow through the endothelium is determined by Darcy’s law and the Kedem-Katchalsky equations, which consider the three-pore model utilized for substance flow across the endothelium. The behavior of these substances within the arterial wall is described by convection–diffusion-reaction equations, while the arterial wall itself is modeled as a hyperelastic material using Yeoh’s model. To accurately evaluate hypertension’s influence, adjustments were made to incorporate wall compression-induced wall compaction by radial compression. This compaction impacts three key variables of the transport phenomena: diffusion, porosity, and permeability. Based on the obtained findings, we can conclude that hypertension significantly augments plaque growth, leading to an over 400% increase in plaque thickness. This effect persists regardless of whether wall mechanics are considered. Tortuosity, arterial wall permeability, and porosity have minimal impact on atheroma plaque growth under normal arterial pressure. However, the atheroma plaque growth changes dramatically in hypertensive cases. In such scenarios, the collective influence of all factors—tortuosity, permeability, and porosity—results in nearly a 20% increase in plaque growth. This emphasizes the importance of considering wall compression due to hypertension in patient studies, where elevated blood pressure and high cholesterol levels commonly coexist.

A Systematic Review and Meta-Analysis on the Role of Bempedoic Acid in Cardiovascular Outcomes for Patients With Statin Intolerance.

Atherosclerosis, a multifaceted pathogenic process affecting the arteries and aorta, poses a significant threat because of its potential to impede or entirely obstruct blood flow by narrowing blood vessels. This intricate progression involves various factors such as dyslipidemia, immunological responses, inflammation, and endothelial dysfunction. The initial phase manifests as the formation of fatty streaks, considered a pivotal hallmark in the inception of atherosclerotic plaques, a process that can commence as early as childhood. Over time, this process evolves, characterized by the thickening of the arterial inner layer (intima) and accumulation of lipid-laden macrophages, commonly known as foam cells, along with the buildup of the extracellular matrix. Subsequent stages witness the proliferation and aggregation of smooth muscle cells, culminating in the formation of atheroma plaques. As these lesions progress, apoptosis can occur in the deeper layers, further recruiting macrophages, which may undergo calcification and transform into atherosclerotic plaques. Notably, mechanisms such as arterial remodeling and intraplaque hemorrhage also contribute significantly to the progression of atherosclerotic cardiovascular disease, although these facets fall beyond the scope of this article. This study aimed to systematically review and conduct a meta-analysis of randomized controlled trials investigating the efficacy and safety of bempedoic acid in statin-intolerant patients with hyperlipidemia and to provide conclusions and recommendations accordingly. A systematic search of databases, such as PubMed, Web of Science, and Embase, will be performed. Only randomized trials will be included comparing bempedoic acid with placebo in statin-intolerant patients. This study aimed to provide a comprehensive understanding of the role of bempedoic acid in managing hyperlipidemia in statin-intolerant patients. In primary prevention, for patients unable to tolerate recommended statins, bempedoic acid was associated with a significant reduction in major adverse cardiovascular events (MACE) as the primary endpoint.

Mitochondria targeted esculetin administration improves insulin resistance and hyperglycemia-induced atherosclerosis in db/db mice.

The development and progression of hyperglycemia (HG) and HG-associated atherosclerosis are exacerbated by mitochondrial dysfunction due to dysregulated mitochondria-derived ROS generation. We recently synthesized a novel mitochondria-targeted esculetin (Mito-Esc) and tested its dose-response therapeutic efficacy in mitigating HG-induced atherosclerosis in db/db mice. In comparison to simvastatin and pioglitazone, Mito-Esc administration resulted in a considerable reduction in body weights and improved glucose homeostasis, possibly by reducing hepatic gluconeogenesis, as indicated by a reduction in glycogen content, non-esterified free fatty acids (NEFA) levels, and fructose 1,6-bisphosphatase (FBPase) activity. Interestingly, Mito-Esc treatment, by regulating phospho-IRS and phospho-AKT levels, greatly improved palmitate-induced insulin resistance, resulting in enhanced glucose uptake in adipocytes and HepG2 cells. Also, and importantly, Mito-Esc administration prevented HG-induced atheromatous plaque formation and lipid accumulation in the descending aorta. In addition, Mito-Esc administration inhibited the HG-mediated increase in VACM, ICAM, and MAC3 levels in the aortic tissue, as well as reduced the serum pro-inflammatory cytokines and markers of senescence. In line with this, Mito-Esc significantly inhibited monocyte adherence to human aortic endothelial cells (HAECs) treated with high glucose and reduced high glucose-induced premature senescence in HAECs by activating the AMPK-SIRT1 pathway. In contrast, Mito-Esc failed to regulate high glucose-induced endothelial cell senescence under AMPK/SIRT1-depleted conditions. Together, the therapeutic efficacy of Mito-Esc in the mitigation of hyperglycemia-induced insulin resistance and the associated atherosclerosis is in part mediated by potentiating the AMPK-SIRT1 axis. KEY MESSAGES: Mito-Esc administration significantly mitigates diabetes-induced atherosclerosis. Mito-Esc improves hyperglycemia (HG)-associated insulin resistance. Mito-Esc inhibits HG-induced vascular senescence and inflammation in the aorta. Mito-Esc-mediated activation of the AMPK-SIRT1 axis regulates HG-induced endothelial cell senescence.

N-Cadherin Targeted Melanin Nanoparticles Reverse the Endothelial-Mesenchymal Transition in Vascular Endothelial Cells to Potentially Slow the Progression of Atherosclerosis and Cancer.

Endothelial-mesenchymal transition (EndoMT) of vascular endothelial cells has recently been considered as a key player in the early progression of a variety of vascular and nonvascular diseases, including atherosclerosis, cancer, and organ fibrosis. However, current strategies attempting to identify pharmacological inhibitors to block the regulatory pathways of EndoMT suffer from poor selectivity, unwanted side effects, and a heterogeneous response from endothelial cells with different origins. Furthermore, EndoMT inhibitors focus on preventing EndoMT, leaving the endothelial cells that have already undergone EndoMT unresolved. Here, we report the design of a simple but powerful nanoparticle system (i.e., N-cadherin targeted melanin nanoparticles) to convert cytokine-activated, mesenchymal-like endothelial cells back to their original endothelial phenotype. We term this process "Reversed EndoMT" (R-EndoMT). R-EndoMT allows the impaired endothelial barriers to recover their quiescence and intactness, with significantly reduced leukocyte and cancer cell adhesion and transmigration, which could potentially stop atheromatous plaque formation and cancer metastasis in the early stages. R-EndoMT is achieved on different endothelial cell types originating from arteries, veins, and capillaries, independent of activating cytokines. We reveal that N-cadherin targeted melanin nanoparticles reverse EndoMT by downregulating an N-cadherin dependent RhoA activation pathway. Overall, this approach offers a different prospect to treat multiple EndoMT-associated diseases by designing nanoparticles to reverse the phenotypical transition of endothelial cells.

Transcription Factor Regulation of Gene Expression Network by ZNF385D and HAND2 in Carotid Atherosclerosis.

Carotid intima-media thickness (CIMT) is a surrogate indicator for atherosclerosis and has been shown to predict cardiovascular risk in multiple large studies. Identification of molecular markers for carotid atheroma plaque formation can be critical for early intervention and prevention of atherosclerosis. This study performed transcription factor (TF) network analysis of global gene expression data focusing on two TF genes, ZNF385D and HAND2, whose polymorphisms have been recently reported to show association with CIMT. Genome-wide gene expression data were measured from pieces of carotid endarterectomy collected from 34 hypertensive patients (atheroma plaque of stages IV and above according to the Stary classification) each paired with one sample of distant macroscopically intact tissue (stages I and II). Transcriptional regulation networks or the regulons were reconstructed for ZNF385D (5644 target genes) and HAND2 (781 target genes) using network inference. Their association with the progression of carotid atheroma was examined using gene-set enrichment analysis with extremely high statistical significance for regulons of both ZNF385D and HAND2 (p < 6.95 × 10-7) suggesting the involvement of expression quantitative loci (eQTL). Functional annotation of the regulon genes found heavy involvement in the immune system's response to inflammation and infection in the development of atherosclerosis. Detailed examination of the regulation and correlation patterns suggests that activities of the two TF genes could have high clinical and interventional impacts on impairing carotid atheroma plaque formation and preventing carotid atherosclerosis.

Relationship between Copper, Zinc, and Copper-to-Zinc Ratio in Hair and Severity of Coronary Artery Disease according to the SYNTAX Score.

Coronary artery disease (CAD) continues to be a foremost contributor to global mortality, and the quest for modifiable risk factors could improve prophylactic strategies. Recent studies suggest a significant role of zinc (Zn) and copper (Cu) deficiency in atheromatous plaque formation. Furthermore, hair was previously described as a valuable source of information on elemental burden during the 6-8 week period before sampling. The aim of this study was to investigate the possibility of correlation between the extent of CAD evaluated with the SYNergy Between PCI With TAXUS and the Cardiac Surgery (SYNTAX) score with Cu and Zn content in hair samples, as well as with the Cu/Zn ratio in a cohort of 130 patients. Our findings describe a statistically significant inverse correlation between Cu content and the Cu/Zn ratio in hair samples and the extent of CAD. In contrast, no significant correlation was found between Zn content and the extent of CAD. Considering the scarcity of existing data on the subject, the analysis of hair samples could yield a novel insight into elemental deficiencies and their potential influence on CAD extent.

Effect of Flavonoids on MCP-1 Expression in Human Coronary Artery Endothelial Cells and Impact on MCP-1-Dependent Migration of Human Monocytes.

The monocyte chemoattractant protein-1 (MCP-1), also known as chemokine (CC motif) ligand 2 (CCL2), is involved in the formation, progression, and destabilization of atheromatous plaques. Flavonoids, found in fruits and vegetables, have been associated with various health-promoting properties, including antioxidant, anti-inflammatory, and cardioprotective effects. In the present study, the flavonoids quercetin, kaempferol, and luteolin, but not cannflavin A, were shown to substantially inhibit interleukin (IL)-1β-induced MCP-1 mRNA and protein expression in human coronary artery endothelial cells (HCAEC). At the functional level, conditioned medium (CM) from IL-1β-stimulated HCAEC caused an increase in the migration of THP-1 monocytes compared with CM from unstimulated HCAEC. However, this induction was suppressed when IL-1β-treated HCAEC were coincubated with quercetin, kaempferol, or luteolin. The functional importance of MCP-1 in IL-1β-induced monocyte migration was supported by experiments showing that neutralization of MCP-1 in the CM of IL-1β-treated HCAEC led to a significant inhibition of migration. In addition, a concentration-dependent induction of monocyte migration in the presence of recombinant MCP-1 was demonstrated. Collectively, the flavonoids quercetin, kaempferol, and luteolin were found to exert potential antiatherogenic effects in HCAEC, challenging further studies with these compounds.

Therapeutic efficacy of mitochondria-targeted esculetin in the improvement of NAFLD-NASH via modulating AMPK-SIRT1 axis

Mitochondrial dysfunction due to deregulated production of mitochondria-derived ROS is implicated in the development and progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). Recently, we synthesized a novel mitochondria-targeted esculetin (Mito-Esc) and investigated its dose–response therapeutic efficacy in mitigating high-fat diet (HFD)-induced NAFLD and NASH in Apoe-/- mice. Mito-Esc administration, compared to simvastatin and pioglitazone, dose-dependently caused a significant reduction in body weight, improved lipid profile, glucose homeostasis, and pro-inflammatory cytokines level. Mito-Esc administration reduced adipose tissue hypertrophy and lipid accumulation presumably by regulating the levels of CD36, PPAR-γ, EBP-α, and their target genes. Mechanistically, Mito-Esc-induced activation of the AMPK1α-SIRT1 axis inhibited pre-adipocyte differentiation. Conversely, Mito-Esc failed to regulate pre-adipocyte differentiation under AMPK/SIRT1 depleted conditions. In parallel, Mito-Esc administration ameliorated HFD-induced steatosis, fibrosis of the liver, and NAFLD-associated atheromatous plaque formation in the aorta. Importantly, Mito-Esc administration inhibited HFD-induced infiltration of macrophages, a marker of steatohepatitis, in the adipose and liver tissues. The results of the in vitro studies showed that Mito-Esc treatment significantly inhibits TGF-β-induced hepatic stellate cell differentiation as well as the fibrotic markers. Consistent with the above observations, Mito-Esc treatment by activating the AMPK-SIRT1 pathway markedly reversed palmitate-induced mitochondrial superoxide production, depolarization of mitochondrial membrane potential, and lipid accumulation in HepG2 cells. Together, the therapeutic efficacy of Mito-Esc in the mitigation of HFD-induced lipotoxicity, and the associated NASH is in part, mediated by potentiating the AMPK-SIRT1 axis.

Effect of the Association of Fixed Oils from Abelmoschus esculentus (L.) Moench, Euterpe oleracea Martius, Bixa orellana Linné and Chronic SM® on Atherogenic Dyslipidemia in Wistar Rats.

Dyslipidemia presents high levels of serum cholesterol and is characterized as a risk factor for cardiovascular diseases, especially for the development of atherosclerosis. E. oleracea oil (OFEO), A. esculentus oil (OFAE), B. orellana oil (OFBO), and Chronic SM® granules (CHR) are rich in bioactive compounds with the potential to treat changes in lipid metabolism. This study investigated the effects of treatments with oils from A. esculentus, E. oleracea, B. orellana, and Chronic SM® on Cocos nucifera L. saturated-fat-induced dyslipidemia. The chromatographic profile showed the majority presence of unsaturated fatty acids in the tested oils. The quantification of tocotrienols and geranylgeraniol in OFBO and CHR was obtained. Treatments with OFEO, OFAE, OFBO, and CHR were able to significantly reduce glycemia, as well as hypertriglyceridemia, total cholesterol, and LDL-cholesterol, besides increasing HDL-cholesterol. The treatments inhibited the formation of atheromatous plaques in the vascular endothelium of the treated rats. The obtained results suggest that the OFEO, OFAE, OFBO, and CHR exhibit antidyslipidemic effects and antiatherogenic activity.

Novel Electrochemiluminescent Immunosensor Using Dual Amplified Signals from a CoFe Prussian Blue Analogue and Au Nanoparticle for the Detection of Lp-PLA2.

Coronary heart disease (CHD) poses an important threat to human health, and its pathogenesis is the formation of atheromatous plaques in coronary ventricles. Compared to other biomarkers, lipoprotein-associated phospholipase A2 (Lp-PLA2), which is involved in multiple processes of atherosclerosis, is a noticeable inflammatory biomarker related to CHD. Herein, using a multifunctional nanocomposite containing a CoFe Prussian blue analogue (PBA) and Au nanoparticles (AuNPs) (AuNPs@CoFe PBA) as a sensing substrate, an electrochemiluminescent (ECL) immunosensor was developed for the highly sensitive detection of Lp-PLA2. Benefiting from the synergistic effect of the PBA and AuNPs, the nanocomposite exhibits excellent peroxidase-like activity and can catalyze the luminol-ECL reaction, amplifying the ECL signal by ∼29-fold. Meanwhile, the enlarged specific surface area of the nanocomposite and the presence of abundant AuNPs allow the immobilization of more antibody proteins, thereby improving the sensing response of the immunosensor. When the target Lp-PLA2 is captured by the antibody on the sensor surface, the sensor emits a reduced ECL signal because of the increased mass and electron transfer resistance due to the formation of the immune complex. Under optimized conditions, the constructed ECL immunosensor exhibits a broad linear range from 1 to 2200 ng/mL and a low detection limit of 0.21 ng/mL. Additionally, the ECL immunosensor exhibits high specificity, stability, and reproducibility. This work provides a new approach to diagnose CHD and broadened the application of the PBA in the field of ECL sensors.

Interplay Among Lipoproteins, Endothelial Cells and Platelets

Epidemiological studies have allowed variables related to coagulation to be implicated in the process of atheromatous plaque formation. These include fibrinogen, factors VIII, VII, and von Willebrand, as well as fibrinolytic activity. It is important to note that the reported changes are reversible and there is a reduction in atherosclerotic disease when hyperlipidemia is corrected. The interference that dyslipidemia makes in the hemostasis system is located in three fundamental points: the endothelial cell, platelets and circulating coagulation factors and fibrinolysis. The lumen of the vessels of the entire cardiovascular system is covered by a single layer of juxtaposed endothelial cells, which are in direct contact with the circulating blood. They separate the blood from the subendothelial matrix, where adhesive proteins important for activating coagulation such as collagen, von Willebrand factor and fibronectin are found. The endothelial cell has multiple functions that, as a whole, protect from the activation of coagulation and thrombus formation. The role of hemostasis in the initial phase of atherogenesis is mainly related to platelet activation. They have a lipoprotein cell membrane containing glycoproteins, which function as important receptors for platelet activation represented by the processes of adhesion, shape change, secretion of granules and aggregation for platelet plug formation.

Protective Effects of a Red Grape Juice Extract against Bisphenol A-Induced Toxicity in Human Umbilical Vein Endothelial Cells.

Human exposure to bisphenol A (BPA) occurs through the ingestion of contaminated food and water, thus leading to endothelial dysfunction, the first signal of atherosclerosis. Vitis vinifera L. (grape) juice is well known for its health-promoting properties, due to its numerous bioactive compounds among which are polyphenols. The aim of this study was to evaluate the protective effect of a red grape juice extract (RGJe) against the endothelial damage induced by BPA in human umbilical vein endothelial cells (HUVECs) as an in vitro model of endothelial dysfunction. Our results showed that RGJe treatment counteracted BPA-induced cell death and apoptosis in HUVECs, blocking caspase 3 and modulating p53, Bax, and Bcl-2. Moreover, RGJe demonstrated antioxidant properties in abiotic tests and in vitro, where it reduced BPA-induced reactive oxygen species as well as restored mitochondrial membrane potential, DNA integrity, and nitric oxide levels. Furthermore, RGJe reduced the increase of chemokines (IL-8, IL-1β, and MCP-1) and adhesion molecules (VCAM-1, ICAM-1, and E-selectin), caused by BPA exposure, involved in the primary phase of atheromatous plaque formation. Overall, our results suggest that RGJe prevents BPA-induced vascular damage modulating specific intracellular mechanisms, along with protecting cells, owing to its antioxidant capability.

Protective Effect of Olive Oil Microconstituents in Atherosclerosis: Emphasis on PAF Implicated Atherosclerosis Theory.

Atherosclerosis is a progressive vascular multifactorial process. The mechanisms underlining the initiating event of atheromatous plaque formation are inflammation and oxidation. Among the modifiable risk factors for cardiovascular diseases, diet and especially the Mediterranean diet (MedDiet), has been widely recognized as one of the healthiest dietary patterns. Olive oil (OO), the main source of the fatty components of the MedDiet is superior to the other "Mono-unsaturated fatty acids containing oils" due to the existence of specific microconstituents. In this review, the effects of OO microconstituents in atherosclerosis, based on data from in vitro and in vivo studies with special attention on their inhibitory activity against PAF (Platelet-Activating Factor) actions, are presented and critically discussed. In conclusion, we propose that the anti-atherogenic effect of OO is attributed to the synergistic action of its microconstituents, mainly polar lipids that act as PAF inhibitors, specific polyphenols and α-tocopherol that also exert anti-PAF activity. This beneficial effect, also mediated through anti-PAF action, can occur from microconstituents extracted from olive pomace, a toxic by-product of the OO production process that constitutes a significant ecological problem. Daily intake of moderate amounts of OO consumed in the context of a balanced diet is significant for healthy adults.

Injury to the tunica media initiates atherogenesis in the presence of hyperlipidemia.

Fatty streaks initiating the formation of atheromatous plaque appear in the tunica intima. The tunica media is not known to be a nidus for lipid accumulation initiating atherogenesis. We assessed changes to the tunica media in response to a micro-injury produced in the pig aorta. In addition, we assessed human carotid endarterectomy plaques for indication of atheroma initiation in the tunica media. Three healthy landrace female pigs underwent laparotomy to inject autologous blood and create micro-hematomas at 6 sites within the tunica media of the infrarenal abdominal aorta. These pigs were fed a high-fat diet (HFD) for 4-12 weeks. Post-mortem aortas from all pigs, including a control group of healthy pigs, were serially stained to detect lipid deposits, vasa vasora (VV), immune cell infiltration and inflammatory markers, as well as changes to the vascular smooth muscle cell (vSMC) compartment. Moreover, 25 human carotid endarterectomy (CEA) specimens were evaluated for their lipid composition in the tunica media and intima. High lipid clusters, VV density, and immune cell infiltrates were consistently observed at 5 out of 6 injection sites under prolonged hyperlipidemia. The hyperlipidemic diet also affected the vSMC compartment in the tunica media adjacent to the tunica adventitia, which correlated with VV invasion and immune cell infiltration. Analysis of human carotid specimens post-CEA indicated that 32% of patients had significantly greater atheroma in the tunica media than in the arterial intima. The arterial intima is not the only site for atherosclerosis initiation. We show that injury to the media can trigger atherogenesis.

Curcumin-Based Nanomedicines in the Treatment of Inflammatory and Immunomodulated Diseases: An Evidence-Based Comprehensive Review

Curcumin (CUR) is a polyphenol extracted from the rhizome of Curcuma longa that possesses potent anti-inflammatory and antioxidant potential. Despite CUR's numerous beneficial effects on human health, it has limitations, such as poor absorption. Nano-based drug delivery systems have recently been applied to improve CUR's solubility and bioavailability and potentialize its health effects. This review investigated the effects of different CUR-based nanomedicines on inflammatory and immunomodulated diseases. PUBMED, EMBASE, COCHRANE, and GOOGLE SCHOLAR databases were searched, and the Scale for Assessment of Narrative Review Articles (SANRA) was used for quality assessment and PRISMA guidelines. Overall, 66 studies were included comprising atherosclerosis, rheumatoid arthritis (RA), Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), inflammatory bowel diseases (IBD), psoriasis, liver fibrosis, epilepsy, and COVID-19. The available scientific studies show that there are many known nanoformulations with curcumin. They can be found in nanosuspensions, nanoparticles, nanoemulsions, solid lipid particles, nanocapsules, nanospheres, and liposomes. These formulations can improve CUR bioavailability and can effectively be used as adjuvants in several inflammatory and immune-mediated diseases such as atheroma plaque formation, RA, dementia, AD, PD, MS, IBD, psoriasis, epilepsy, COVID-19, and can be used as potent anti-fibrotic adjuvants in fibrotic liver disease.

Tongxinluo enhances the effect of atorvastatin on the treatment of atherosclerosis with chronic obstructive pulmonary disease by maintaining the pulmonary microvascular barrier.

Atherosclerosis (AS) is a common comorbidity of chronic obstructive pulmonary disease (COPD), and systemic inflammation is an important mechanism of COPD with AS. Tongxinluo (TXL) improves the function of vascular endothelial cells. We aimed to prove that impairment of pulmonary microvascular barrier function is involved in COPD-mediated aggravation of AS and investigate whether TXL enhances the effect of Ato (atorvastatin) on COPD with AS by protecting pulmonary microvascular endothelial barrier function. In vivo, a COPD with atherosclerotic apolipoprotein E knockout (AS ApoE-/-) mouse model was established by cigarette smoke combined with a high-fat diet. The animals were administered TXL, Ato, and TXL + Ato once a day for 20 weeks. Lung function, lung microvascular permeability, lung inflammation, systemic inflammation, serum lipid levels, atheromatous plaque formation, and endothelial damage biomarkers were measured. In vitro, human pulmonary microvascular endothelial cells (HPMECs) were pretreated with TXL and incubated with cigarette smoke extract to establish the model. The permeability of the endothelial monolayer, inflammatory cytokines, endothelial damage biomarkers, and tight junction (Tj) proteins were determined. Cigarette smoking significantly exacerbated the high-fat diet-induced pulmonary function decline, pulmonary microvascular endothelial barrier dysfunction, inflammation, and atherosclerotic plaques. These changes were reversed by TXL-Ato; the combination was more effective than Ato alone. Furthermore, TXL protected the HPMEC barrier and inhibited inflammation in HPMECs. COPD aggravates AS, possibly through the destruction of pulmonary microvascular barrier function; thus, lung inflammation triggers systemic inflammation. In treating COPD with AS, TXL enhances the antiatherosclerotic effect of Ato, protecting the pulmonary microvascular barrier.

Pretreatment of macrophage-membrane-coated nanoparticles for therapeutical targeting of P. gingivalis-accelerated atherosclerosis

Atherosclerosis (AS) as a chronically inflammatory disease is the mainly cause of mortality worldwide. Porphyromonas gingivalis (P. gingivalis, Pg), one primary pathogen in periodontitis (PD), has been reported to promote the progression of atherosclerosis via inducing infectiously triggered immune response, thus accelerating atheromatous plaque formation. However, limited therapeutic potency has been achieved using traditional drug treatment due to the existence of Pg and low concentration of drug reached in AS, reminding us to develop a new drug delivery strategy. In this study, to simultaneously realize the pathogen elimination and inflammation resolution in Pg-infected region, the PLGA-simvastatin-chitosan-metronidazole nanoparticles (STNPs) were coated with Pg-treated macrophage membranes (MM/STNPs). These nanoparticles obviously eliminated the amount of Pg and effectively switched the activation of macrophages from an inflammatory M1-like state to a more immunosuppressive M2-like phenotype. Using Pg-treated macrophage membrane (MM), the MM/STNPs were efficiently targeted in both atheromatous plaque and periodontal tissue in vivo. Importantly, MM/STNPs injection simultaneously diminished the atheromatous plaque formation in AS and rejuvenated the alveolar bone loss in PD. Based on this specific Pg-targeted delivery, the biomimetic nanoparticles provide a new approach for the targeting strategy in the treatment of Pg-accelerated AS.

Synopsis of Biomarkers of Atheromatous Plaque Formation, Rupture and Thrombosis in the Diagnosis of Acute Coronary Syndromes.

Acute coronary syndrome is the main cause of mortality and morbidity worldwide and early diagnosis is a challenge for clinicians. Though cardiac Troponin, the most commonly used biomarker, is the gold standard for myocardial necrosis, it is blind for ischemia without necrosis. Therefore, ideal biomarkers are essential in the care of patients presenting with symptoms suggestive of cardiac ischemia. The ideal biomarker or group of biomarkers of atheromatous plaque formation, rupture and thrombosis for timely and accurate diagnosis of acute coronary syndrome is a current need. Therefore, we discuss the existing understanding and future of biomarkers of atheromatous plaque formation, rupture and thrombosis of acute coronary syndrome in this review. Keywords were searched from Medline, ISI, IBSS and Google Scholar databases. Further, the authors conducted a manual search of other relevant journals and reference lists of primary articles. The development of high-sensitivity troponin assays facilitates earlier exclusion of acute coronary syndrome, contributing to a reduced length of stay at the emergency department, and earlier treatment resulting in better outcomes. Although researchers have investigated biomarkers of atheromatous plaque formation, rupture and thrombosis to help early diagnosis of cardiac ischemia, most of them necessitate validation from further analysis. Among these biomarkers, pregnancy-associated plasma protein-A, intercellular adhesion molecule-1, and endothelial cell-specific molecule- 1(endocan) have shown promising results in the early diagnosis of acute coronary syndrome but need further evaluation. However, the use of a combination of biomarkers representing varying pathophysiological mechanisms of cardiac ischemia will support risk assessment, diagnosis and prognosis in these patients and this is the way forward.

Bioimpedance Sensing of Implanted Stent Occlusions: Smart Stent.

Coronary artery disease is one of the most common diseases in developed countries and affects a large part of the population of developing countries. Preventing restenosis in patients with implanted stents is an important current medical problem. The purpose of this work is to analyse the viability of bioimpedance sensing to detect the formation of atheromatous plaque in an implantable stent. Simulations in COMSOL Multiphysics were performed to analyse the performance of the proposed bioimpedance sensing system, based on the Sheffield technique. Both non-pathological and pathological models (with atheromatous plaque), including the flow of blood were considered. Simulations with the non-pathological model showed a homogeneous distribution of the measured current intensity in the different electrodes, for every configuration. On the other hand, simulations with the pathological model showed a significant decrease of the measured current intensity in the electrodes close to the simulated atheromatous plaque. The presence of the atheromatous plaque can, therefore, be detected by the system with a simple algorithm, avoiding the full reconstruction of the image and the subsequent computational processing requirements.

Proliferation and apoptosis of smooth muscle and endothelial cells with immune inflammation in cerebrovascular diseases on atherosclerosis background

The aim – to determine the role of vascular wall cells proliferation and apoptosis with the participation of immune inflammation, and their impact on the development of cerebrovascular disease (CVD) development on the atherosclerosis (AS) background. Materials and methods. We studied 50 cases of death with ischemic stroke and 50 cases of death with hemorrhagic stroke on the cerebral vessels AS background. Outcomes. Lymphocytes are one of the atheroma components and are mainly localised at the sites of plaque rupture in close contact with macrophages and smooth muscle cells. Smooth muscle cells are able to synthesize important collagen and elastin for the vascular wall, but potentiated apoptosis of smooth muscle cells may contribute to destabilisation and plaque rupture. Smooth muscle cells apoptosis was triggered by proinflammatory factors and took place with the participation of cytotoxic T-lymphocytes (T-killers) therefore in the atherosclerotic lesions focus we registered an accumulation of multitude cytotoxic T-lymphocytes. Conclusions. The macrophages and smooth muscle cells susceptibility to apoptosis was significantly higher directly in the atheroma, but macrophage apoptosis is a useful process for the atherosclerotic plaque stability. Desquamation and endothelial cell apoptosis are interrelated processes that play an important role in atheromatous plaque formation.