Plaque stabilisation

Understanding the pathways involved in the formation and stability of the core and shell regions of a platelet-rich arterial thrombus may result in new ways to treat arterial thrombosis. The distinguishing feature between these two regions is the absence of fibrin in the shell which indicates that in vitro flow-based assays over thrombogenic surfaces, in the absence of coagulation, can be used to resemble this region. In this study, we have investigated the contribution of Syk tyrosine kinase in the stability of platelet aggregates (or thrombi) formed on collagen or atherosclerotic plaque homogenate at arterial shear (1000 s-1 )...

One of the hallmarks of Alzheimer's disease (AD) are deposits of amyloid-beta (Aβ) protein in amyloid plaques in the brain. The Aβ peptide exists in several forms, including full-length Aβ1-42 and Aβ1-40 - and the N-truncated species, pyroglutamate Aβ3-42 and Aβ4-42, which appear to play a major role in neurodegeneration. We previously identified a murine antibody (TAP01), which binds specifically to soluble, non-plaque N-truncated Aβ species. By solving crystal structures for TAP01 family antibodies bound to pyroglutamate Aβ3-14, we identified a novel pseudo β-hairpin structure in the N-terminal region of Aβ and show that this underpins its unique binding properties...

BACKGROUND: Abdominal aortic calcifications were already ubiquitous in ancient populations from all continents. Although nowadays generally considered as an innocent end stage of stabilised atherosclerotic plaques, increasing evidence suggests that arterial calcifications contribute to cardiovascular risk. In this review we address abdominal aortic calcification from an evolutionary perspective and review the literature on histology, prevalence, risk factors, clinical outcomes and pharmacological interventions of abdominal aortic calcification...

In this review, we discuss the synaptic aspects of Tau pathology occurring during Alzheimer's disease (AD) and how this may relate to memory impairment, a major hallmark of AD. Whilst the clinical diagnosis of AD patients is a loss of working memory and long-term declarative memory, the histological diagnosis is the presence of neurofibrillary tangles of hyperphosphorylated Tau and Amyloid-beta plaques. Tau pathology spreads through synaptically connected neurons to impair synaptic function preceding the formation of neurofibrillary tangles, synaptic loss, axonal retraction and cell death...

Reduction of glucose is the hallmark of diabetes therapy proven to reduce micro- and macro-vascular risk in patients with type 1 diabetes. However glucose-lowering efficacy trials in type 2 diabetes didn't show major cardiovascular benefit. Then, a paradigm change in the treatment of patients with type 2 diabetes has emerged due to the introduction of new blood glucose-lowering agents. Cardiovascular endpoint studies have proven HbA1c-independent cardioprotective effects for GLP-1 receptor agonists and SGLT-2 inhibitors...

Collagen is an important protein in various biological functions such as providing elasticity and waterproofing to the skin, structural stability to the cells in connective tissues (e.g. tendons, and bone) and stabilisation of atherosclerotic plaques. Collagen as a peptide with a peculiar triple helical structure is majorly composed of glycine and proline amino acids and is synthesised by fibroblasts via intracellular and extracellular mechanisms. Collagen plays an important role in wound healing, bone repair and plaque build-up during atherosclerosis...

BACKGROUND AND AIM: Aβ1-42 is an amyloidogenic peptide found within senile plaques extracted from those who died with a diagnosis of Alzheimer's disease. The potent neurotoxicity of this peptide is related to its propensity to form aggregated conformations in vivo, a process that is influenced by the species and concentration of metal ions present within the local environment. This study examines the impact of different metals upon the early aggregatory behaviour and size of Aβ1-42 under simulated physiological conditions...

Vascular smooth muscle cells (VSMCs) are key participants in both early and late-stage atherosclerosis. VSMCs invade the early atherosclerotic lesion from the media, expanding lesions, but also forming a protective fibrous cap rich in extracellular matrix to cover the 'necrotic' core. Hence, VSMCs have been viewed as plaque-stabilising, and decreased VSMC plaque content - often measured by expression of contractile markers - associated with increased plaque vulnerability. However, the emergence of lineage-tracing and transcriptomic studies has demonstrated that VSMCs comprise a much larger proportion of atherosclerotic plaques than originally thought, demonstrate multiple different phenotypes in vivo, and have roles that might be detrimental...

The rupture of unstable/vulnerable atherosclerotic plaques is the major cause of cardiovascular mortality/morbidity. Despite significant limitations in our understanding and ability to identify unstable plaque pathology and prevent plaque rupture, most atherosclerosis research utilises preclinical animal models exhibiting stable atherosclerosis. Here, we introduce the Tandem Stenosis (TS) mouse model that reflects plaque instability/rupture as seen in patients. The TS model involves dual ligation of the right carotid artery, leading to locally predefined unstable atherosclerosis in hypercholesterolaemic mice...

BACKGROUND: Sevoflurane may reduce the occurrence of major adverse cardiovascular events (MACCEs) in surgical patients, although the mechanisms are poorly understood. We hypothesised that sevoflurane stabilises atherosclerotic plaques by inhibiting inflammation and enhancing prolyl-4-hydroxylase α1 (P4Hα1), the rate-limiting subunit for the P4H enzyme essential for collagen synthesis. METHODS: We established a vulnerable arterial plaque model in apolipoprotein E-knockout mice (ApoE-/- ) fed a high-fat diet that underwent daily restraint/noise stress, with/without a single prior exposure to sevoflurane for 6 h (1-3%; n=30 per group)...

Improvements in oral health including increased retention of natural teeth have given rise to a partially dentate older population. Replacement of missing natural teeth is important to improve function, aesthetics and quality of life for this patient group. A variety of options are available to replace missing teeth in partially dentate older adults, including fixed, removable and implant retained prostheses. This article will discuss the provision of removable partial dentures including treatment planning and denture design...

Ion-releasing materials (containing fluoride and boron, for example) have shown caries-preventive effects in vitro. The purpose of the present study was to investigate the impact of multi-ion-releasing coating material on pH stabilisation, plaque accumulation and the bacterial composition of dental plaque during a time period of 90 days. The null hypothesis tested here was that the evaluated material would not show any differences in pH stabilisation, plaque accumulation or bacterial composition compared with control material...

Current data suggest that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing corona virus disease-19 (COVID-19) seems to follow a more severe clinical course in patients with cardiovascular disease (CVD), hypertension, and overweight/obesity. It appears that lipid-lowering pharmacological interventions, in particular statins, might reduce the risk of cardiovascular complications caused by COVID-19 and might potentially have an additional antiviral activity. It has been shown that high cholesterol levels are associated with more lipid rafts, subdomains of the plasma membrane that can harbour angiotensin-converting enzyme 2 (ACE2) receptors for the S-protein of SARS-CoV-2...

BACKGROUND: In patients with stable coronary heart disease, it is not known whether achievement of standard of care (SOC) targets in addition to evidence-based medicine (EBM) is associated with lower major adverse cardiovascular events (MACE): cardiovascular death, myocardial infarction, and stroke. METHODS: EBM use was recommended in the STabilisation of Atherosclerotic plaque By Initiation of darapLadIb TherapY trial. SOC targets were blood pressure (BP) <140/90 mm Hg and low-density lipoprotein-cholesterol (LDL-C) <100 mg/dL and <70 mg/dL...

BACKGROUND: An increasing body of evidence suggests that inflammation plays a key role in stroke, in particular stroke of atherosclerotic origin. Anti-inflammatory medications are a widely heterogeneous group of drugs that are used to suppress the innate inflammatory pathway and thus prevent persistent or recurrent inflammation. Anti-inflammatory agents have the potential to stabilise atherosclerotic plaques by impeding the inflammatory pathway. By targeting specific cytokines, the inflammatory pathway may be interrupted at various stages...

BACKGROUND: Abdominal aortic calcifications were already ubiquitous in ancient populations from all continents. Although nowadays generally considered as an innocent end stage of stabilised atherosclerotic plaques, increasing evidence suggests that arterial calcifications contribute to cardiovascular risk. In this review we address abdominal aortic calcification from an evolutionary perspective and review the literature on histology, prevalence, risk factors, clinical outcomes and pharmacological interventions of abdominal aortic calcification...

Background: In patients with non-cardio-embolic stroke, atorvastatin 80 mg/day reduced the relative risk of recurrent stroke by 16%, and a post hoc analysis showed that achieving an LDL-c of less than 70 mg/dL reduced the relative risk by 28% as compared to an on-treatment LDL of 100 mg/dL or more. Current guidelines from the French drug agency recommend treating with a statin after an ischaemic stroke to a target of less than 100 mg/dL, but no study directly tested LDL-c targets. The Treat Stroke to Target (TST) trial will compare the efficacy of achieving an LDL-c of less than 70 mg/dL versus an achieved LDL-c of 100 ± 10 mg/dL for secondary prevention in patients with recent ischaemic stroke of atherosclerotic origin...

Objectives The primary objective of this review was to determine the effectiveness of interdental cleaning per se as a stand-alone treatment, and then with the addition of tooth-brushing or a brushing device as a comparator. The ecological plaque model within which biofilm modification is key to stabilisation of periodontal inflammation. Thus, the control of plaque biofilms has a positive impact on reducing periodontal diseases and caries in the population.1 A secondary objective of the review was to carry out cross-sectional analysis of the effectiveness of different interdental cleaning aid groups (ICA) to ascertain which ICA emerged as the most effective in removing bacterial plaque...

Dysglycaemia (i.e. type 2 diabetes mellitus or impaired glucose tolerance) is not only common in patients with cardiovascular disease but increases the risk for future cardiovascular complications. Hyperglycaemia, the hallmark of diabetes, has since long been considered to be the link between diabetes and cardiovascular disease. Diabetes is, however, a complex, multifactorial disorder to which, for example, insulin resistance, endothelial dysfunction and factors such as increased thrombogenicity, hypertension and dyslipidaemia contribute...

OBJECTIVES: To determine if chewing gum containing casein phosphopeptide stabilised amorphous calcium phosphate (CPP-ACP) promoted an increase in the abundance ofStreptococcus sanguinis and other species associated with dental health in supragingival plaque in a clinical study. MATERIALS AND METHODS: Nineteen participants were recruited for a three-leg cross-over, randomised, controlled clinical trial. Participants chewed a sugar-free gum with or without CPP-ACP six times daily for 20 min over two weeks...