scholarly journals Molecular Pathogenesis of Atherosclerosis and Implication for Therapy

2020 ◽  
Vol 9 (2) ◽  
Author(s):  
Jeanne AP
Keyword(s):  
Risk Factors ◽  
Foam Cell ◽  
Plaque Rupture ◽  
Cell Formation ◽  
Clinical Manifestations ◽  
Individual Risk ◽  
Foam Cell Formation ◽  
Initiation Factors ◽  
The Individual ◽  
Individual Risk Factors

A growing body of evidence supports the role of infl ammation in the pathogenesis of atherosclerosis. However, the supposed initiation factors of atherogenesis are infection and change in shear stress on certain location, leading to attachment of LDL and subsequent oxidation. The pathway activated are the NFkB and TGFβ leading to endothelial dysfunction and production of infl ammatory cytokines and adhesion factors followed by recruitment of infl ammatory cells to the site, oxLDL internalization and foam cell formation in the fatty streak that later develop into atherosclerotic plaque. Further, p53signaling causes apoptosis leading to plaque rupture, platelet activation and aggregation ending in clinical manifestations. Moreover, numerous individual risk factors might aggravate the condition, and the progress might take decades depending on the balance of pro and anti atherogenic factors. Therefore, management of atherosclerosis addressing the individual risk factors using drugs with various properties coping with the molecular basis especially infl ammation is beneficial.

scholarly journals Relationship Between Autophagy and Metabolic Syndrome Characteristics in the Pathogenesis of Atherosclerosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Jing Xu ◽  
Munehiro Kitada ◽  
Yoshio Ogura ◽  
Daisuke Koya
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Plaque Rupture ◽  
Cell Formation ◽  
Degradation Process ◽  
Vascular Wall ◽  
Foam Cell Formation ◽  
Plaque Instability

Atherosclerosis is the main cause of mortality in metabolic-related diseases, including cardiovascular disease and type 2 diabetes (T2DM). Atherosclerosis is characterized by lipid accumulation and increased inflammatory cytokines in the vascular wall, endothelial cell and vascular smooth muscle cell dysfunction and foam cell formation initiated by monocytes/macrophages. The characteristics of metabolic syndrome (MetS), including obesity, glucose intolerance, dyslipidemia and hypertension, may activate multiple mechanisms, such as insulin resistance, oxidative stress and inflammatory pathways, thereby contributing to increased risks of developing atherosclerosis and T2DM. Autophagy is a lysosomal degradation process that plays an important role in maintaining cellular metabolic homeostasis. Increasing evidence indicates that impaired autophagy induced by MetS is related to oxidative stress, inflammation, and foam cell formation, further promoting atherosclerosis. Basal and mild adaptive autophagy protect against the progression of atherosclerotic plaques, while excessive autophagy activation leads to cell death, plaque instability or even plaque rupture. Therefore, autophagic homeostasis is essential for the development and outcome of atherosclerosis. Here, we discuss the potential role of autophagy and metabolic syndrome in the pathophysiologic mechanisms of atherosclerosis and potential therapeutic drugs that target these molecular mechanisms.

Risk Factor Analysis for Injuries in Football Players

2000 ◽  
Vol 28 (5_suppl) ◽  
pp. 69-74 ◽  
Author(s):  
Jiri Dvorak ◽  
Astrid Junge ◽  
Jiri Chomiak ◽  
Toni Graf-Baumann ◽  
Lars Peterson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Wide Spectrum ◽  
Practical Experience ◽  
Individual Risk ◽  
Football Players ◽  
Psychosocial Characteristics ◽  
The Individual ◽  
Individual Risk Factors ◽  
Physical Findings ◽  
Baseline Examination

Review of the literature shows that information concerning risk factors for football injuries is incomplete and partly contradictory. The aim of this study was to analyze the influence of medical history, physical findings, football skills, and football performance, as well as psychosocial characteristics on the occurrence and severity of football injuries. The prospective outline of the study was as follows: after a baseline examination was performed to ascertain possible predictors of injury, all players were followed up weekly for 1 year to register subsequent injuries and complaints. Two hundred sixty-four of 398 players (67%) had complete weekly follow-ups over 1 year. A majority of the players ( N = 216; 82%) were injured during the observation period. In comparing injured and uninjured players, several differences were observed. To create a multidimensional predictor score for football injuries, 17 risk factors were selected. These risk factors covered a wide spectrum, such as previous injuries, acute complaints, inadequate rehabilitation, poor health awareness, high life-event stress, playing characteristics, poor reaction time, poor endurance, and insufficient preparation for games. By summing up the individual risk factors, a predictive sum was calculated for each player. The more risk factors present at the baseline examination, the higher the probability of that player incurring an injury in the ensuing year. Using two risk factors as the cut-off score, more than 80% of the players were correctly classified as to whether they went on to incur an injury. Based on these findings, knowledge from the literature, and practical experience, possibilities for a prevention program are suggested.

Abstract P346: Modeling Novel Biomarkers with Individual Risk Factors and an “Improved” Bayes Approach are Preferred Strategies for Assessing Predictive Utility of Biomarkers

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Vanessa Xanthakis ◽  
Michael J Pencina ◽  
Lisa M Sullivan
Keyword(s):  
Risk Factors ◽  
Risk Score ◽  
Absolute Risk ◽  
Individual Risk ◽  
Composite Risk ◽  
The Individual ◽  
Individual Risk Factors ◽  
Standard Risk ◽  
Prior Risk ◽  
Bayes Approach

Given the rapid growth of new prognostic biomarkers, it is critical to assess their incremental utility for risk prediction while considering standard risk factors. This assessment may be influenced by the approach used to model new biomarkers. We hypothesized that the performance of a putative biomarker is best assessed by adding it to a model that includes standard risk factors as individual variables, as compared to adding it to a composite risk score (based on standard risk factors) estimated from the current study or to a composite risk score from a published study. We also compared 3 approaches of adjusting the prior absolute risk of an event using the information from a new biomarker, when data regarding prior risk are limited, hypothesizing that conditioning the biomarker residuals on prior risk (Improved Bayes approach) or adjusting the intercept of a model that includes the prior risk estimate are superior to the Naïve Bayes approach. Incremental performance was evaluated by comparing measures of improvement in discrimination. Using 1000 simulated datasets, similar incremental performance was observed when a putative biomarker was added to a model with the individual risk factors as compared to adding it to a model with a risk score estimated from the current study. Including a biomarker in a model with a published risk score resulted in an overestimation of its contribution ( Table ).These findings were supported by Framingham Heart Study data predicting incident atrial fibrillation using CRP and BNP.The Improved Bayes approach was a better strategy for updating the prior risk estimate as compared to the Naïve Bayes approach, using information from a new biomarker (Table). Our theoretical and empirical results identified that adding a new biomarker into a multivariable prediction model that includes the individual risk factors is the preferred strategy for assessing the incremental yield of a novel biomarker, and using the Naive Bayes approach (when information on the prior absolute risk of an event is scarce) is suboptimal.

scholarly journals Association of antecedent cardiovascular risk factor levels and trajectories with cardiovascular magnetic resonance-derived cardiac function and structure

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Roberto Lorbeer ◽  
Susanne Rospleszcz ◽  
Christopher L. Schlett ◽  
Sophia D. Rado ◽  
Barbara Thorand ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Cardiac Function ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Individual Risk ◽  
The Individual ◽  
And Function ◽  
Individual Risk Factors

Abstract Background The association of longitudinal trajectories of cardiovascular risk factors with cardiovascular magnetic resonance (CMR)-measures of cardiac structure and function in the community is not well known. Therefore we aimed to relate risk factor levels from different examination cycles to CMR-measures of the left ventricle (LV) and right ventricle in a population-based cohort. Methods We assessed conventional cardiovascular disease risk factors in 349 participants (143 women; aged 25–59 years) at three examination cycles (Exam 1 [baseline], at Exam 2 [7-years follow-up] and at Exam 3 [14-years follow-up]) of the KORA S4 cohort and related single-point measurements of individual risk factors and longitudinal trajectories of these risk factors to various CMR-measures obtained at Exam 3. Results High levels of diastolic blood pressure, waist circumference, and LDL-cholesterol at the individual exams were associated with worse cardiac function and structure. Trajectory clusters representing higher levels of the individual risk factors were associated with worse cardiac function and structure compared to low risk trajectory clusters of individual risk factors. Multivariable (combining different risk factors) trajectory clusters were associated with different cardiac parameters in a graded fashion (e.g. decrease of LV stroke volume for middle risk cluster β = − 4.91 ml/m2, 95% CI − 7.89; − 1.94, p < 0.01 and high risk cluster β = − 7.00 ml/m2, 95% CI − 10.73; − 3.28, p < 0.001 compared to the low risk cluster). The multivariable longitudinal trajectory clusters added significantly to explain variation in CMR traits beyond the multivariable risk profile obtained at Exam 3. Conclusions Cardiovascular disease risk factor levels, measured over a time period of 14 years, were associated with CMR-derived measures of cardiac structure and function. Longitudinal multivariable trajectory clusters explained a greater proportion of the inter-individual variation in cardiac traits than multiple risk factor assessed contemporaneous with the CMR exam.

scholarly journals Deletion or Inhibition of NOD1 Favors Plaque Stability and Attenuates Atherothrombosis in Advanced Atherogenesis

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2067 ◽  
Author(s):  
Silvia González-Ramos ◽  
Victoria Fernández-García ◽  
Miriam Recalde ◽  
Cristina Rodríguez ◽  
José Martínez-González ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Foam Cell ◽  
Plaque Rupture ◽  
Primary Cultures ◽  
Cell Formation ◽  
Thin Layers ◽  
Foam Cell Formation ◽  
Aortic Sinus ◽  
Apoptotic Activity ◽  
Detection Of Biomarkers

Atherothrombosis, the main cause of acute coronary syndromes (ACS), is characterized by the rupture of the atherosclerotic plaque followed by the formation of thrombi. Fatal plaque rupture sites show large necrotic cores combined with high levels of inflammation and thin layers of collagen. Plaque necrosis due to the death of macrophages and smooth muscle cells (SMCs) remains critical in the process. To determine the contribution of the innate immunity receptor NOD1 to the stability of atherosclerotic plaque, Apoe−/− and Apoe−/− Nod1−/− atherosclerosis prone mice were placed on a high-fat diet for 16 weeks to assess post-mortem advanced atherosclerosis in the aortic sinus. The proliferation and apoptosis activity were analyzed, as well as the foam cell formation capacity in these lesions and in primary cultures of macrophages and vascular SMCs obtained from both groups of mice. Our results reinforce the preeminent role for NOD1 in human atherosclerosis. Advanced plaque analysis in the Apoe−/− atherosclerosis model suggests that NOD1 deficiency may decrease the risk of atherothrombosis by decreasing leukocyte infiltration and reducing macrophage apoptosis. Furthermore, Nod1−/− SMCs exhibit higher proliferation rates and decreased apoptotic activity, contributing to thicker fibrous caps with reduced content of pro-thrombotic collagen. These findings demonstrate a direct link between NOD1 and plaque vulnerability through effects on both macrophages and SMCs, suggesting promising insights for early detection of biomarkers for treating patients before ACS occurs.

scholarly journals DETERMINANTS OF NEET (NOT IN EMPLOYMENT, EDUCATION OR TRAINING) ON THE POLISH LABOUR MARKET

2022 ◽  
Author(s):  
Anna M. Rak
Keyword(s):  
Risk Factors ◽  
Young People ◽  
Labour Market ◽  
Formal Education ◽  
Individual Risk ◽  
Job Seeking ◽  
Employment Education ◽  
The Individual ◽  
Individual Risk Factors ◽  
The Eu

The principal purpose of the study is to identify the individual risk factors of young people becoming the NEET generation on the Polish labour market. The first part of the paper comprises a literature-based overview of definitions of the NEET category based and a presentation of the risk factors of young people becoming NEET. The second part presents the results of empirical analyses conducted employing a questionnaire on a group of 120 individuals, aged 15 through 30, who met all criteria of the NEET definition set forth by the Employment Committee of the EU. The research demonstrates that among the major determinants of young people becoming NEET are financial hardship of their households, low motivation to continue formal education or change professional qualifications, and low level of job-seeking activity.

scholarly journals The Initial Human Atherosclerotic Lesion and Lipoprotein Modification—A Deep Connection

2021 ◽  
Vol 22 (21) ◽  
pp. 11488
Author(s):  
Michael Torzewski
Keyword(s):  
Plasma Levels ◽  
Foam Cell ◽  
Hydrolytic Enzymes ◽  
Cell Formation ◽  
Clinical Manifestations ◽  
Atherosclerotic Lesion ◽  
Foam Cell Formation ◽  
Lysosomal Storage ◽  
Atherosclerotic Lesions ◽  
Micro Rnas

Atherosclerosis research typically focuses on the evolution of intermediate or advanced atherosclerotic lesions rather than on prelesional stages of atherogenesis. Yet these early events may provide decisive leads on the triggers of the pathologic process, before lesions become clinically overt. Thereby, it is mandatory to consider extracellular lipoprotein deposition at this stage as the prerequisite of foam cell formation leading to a remarkable accumulation of LDL (Low Density Lipoproteins). As progression of atherosclerosis displays the characteristic features of a chronic inflammatory process on the one hand and native LDL lacks inflammatory properties on the other hand, the lipoprotein must undergo biochemical modification to become atherogenic. During the last 25 years, evidence was accumulated in support of a different concept on atherogenesis proposing that modification of native LDL occurs through the action of ubiquitous hydrolytic enzymes (enzymatically modified LDL or eLDL) rather than oxidation and contending that the physiological events leading to macrophage uptake and reverse transport of eLDL first occur without inflammation (initiation with reversion). Preventing or reversing initial atherosclerotic lesions would avoid the later stages and therefore prevent clinical manifestations. This concept is in accordance with the response to retention hypothesis directly supporting the strategy of lowering plasma levels of atherogenic lipoproteins as the most successful therapy for atherosclerosis and its sequelae. Apart from but unquestionable closely related to this concept, there are several other hypotheses on atherosclerotic lesion initiation favoring an initiating role of the immune system (‘vascular-associated lymphoid tissue’ (VALT)), defining foam cell formation as a variant of lysosomal storage disease, relating to the concept of the inflammasome with crystalline cholesterol and/or mitochondrial DAMPs (damage-associated molecular patterns) being mandatory in driving arterial inflammation and, last but not least, pointing to miRNAs (micro RNAs) as pivotal players. However, direct anti-inflammatory therapies may prove successful as adjuvant components but will likely never be used in the absence of strategies to lower plasma levels of atherogenic lipoproteins, the key point of the perception that atherosclerosis is not simply an inevitable result of senescence. In particular, given the importance of chemical modifications for lipoprotein atherogenicity, regulation of the enzymes involved might be a tempting target for pharmacological research.

scholarly journals Exploration of the risk factors contained within the UK’s existing domestic abuse risk assessment tool (DASH): do these risk factors have individual predictive validity regarding recidivism?

2017 ◽  
Vol 9 (1) ◽  
pp. 58-68 ◽  
Author(s):  
Louise Almond ◽  
Michelle McManus ◽  
David Brian ◽  
Daniel Peter Merrington
Keyword(s):  
Risk Factors ◽  
Risk Assessment ◽  
Assessment Tool ◽  
Domestic Abuse ◽  
Criminal History ◽  
Risk Assessment Tool ◽  
Individual Risk ◽  
Content Type ◽  
The Individual ◽  
Individual Risk Factors

Purpose The purpose of this paper is to explore risk factors contained in the existing UK domestic abuse (DA) risk assessment tool: domestic abuse, stalking and harassment and honour-based violence (DASH) for individual predictive validity of DA recidivism using data from Devon and Cornwall Constabulary. Design/methodology/approach In total, 1,441 DA perpetrators were monitored over a 12-month period, and 270 (18.7 per cent) went on to commit a further DA offence. The individual risk factors which were associated and predictive of increased risk of recidivism were identified. Findings Only four of the individual risk factors were significantly associated with an increased risk of DA recidivism: “criminal history”, “problems with alcohol”, “separation” and “frightened”. Therefore, 21 of the risk factor items analysed could not discriminate between non-recidivist and recidivist perpetrators. Only two risk factors were able to significantly predict the recidivist group when compared to the non-recidivist group. These were identified as “criminal history” and “separated”. Of those who did commit a further DA offence in the following 12 months, 133 were violent and 137 were non-violent. The risk factors associated with these types of recidivism are identified. Practical implications The implications for UK police practice and the DASH risk assessment tool are discussed. By identifying key individual factors that can prioritise those individuals likely to recidivate and the severity of that recidivism, this could assist police decision making regarding the response and further prevention of DA incidents. The validation of association between individual factors and DA recidivism should improve the accuracy of risk levels. Originality/value This is the first large-scale validation of the individual risk factors contained within the UK’s DA risk assessment tool. It should be noted that the validity of the DASH tool itself was not examined within the current study.

Update on lipids, inflammation and atherothrombosis

2011 ◽  
Vol 105 (S 06) ◽  
pp. S34-S42 ◽  
Author(s):  
Robert Storey ◽  
Gemma Vilahur ◽  
Lina Badimon
Keyword(s):  
Smooth Muscle ◽  
Tissue Factor ◽  
Foam Cell ◽  
Plaque Rupture ◽  
Thrombus Formation ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Local Inflammatory Response ◽  
Endothelial Layer ◽  
Ldl Particles

SummaryAtherosclerosis is an inflammatory disease that involves the arterial wall and is characterised by the progressive accumulation of lipids in the vessel wall. The first step is the internalisation of lipids (LDL) in the intima with endothelial activation which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. These events increase LDL particles accumulation in the extracellular matrix where they aggregate/fuse, are retained by proteoglycans and become targets for oxidative and enzymatic modifications. In turn, retained pro-atherogenic LDLs enhance selective leukocyte recruitment and attachment to the endothelial layer inducing their transmigration across the endothelium into the intima. While smooth muscle cell numbers decline with the severity of plaque progression, monocytes differentiate into macrophages, a process associated with the upregulation of pattern recognition receptors including scavenger receptors and Toll-like receptors leading to foam cell formation. Foamcells release growth factors, cytokines, metalloproteinases and reactive oxygen species all of which perpetuate and amplify the vascular remodelling process. In addition, macrophages release tissue factor that, upon plaque rupture, contributes to thrombus formation. Smooth muscle cells exposed in eroded lesions are also able to internalise LDL through LRP-1 receptors acquiring a pro-thrombotic phenotype and releasing tissue factor. Platelets recognise ligands in the ruptured or eroded atherosclerotic plaque, initiate platelet activation and aggregation leading to thrombosis and to the clinical manifestation of the atherothrombotic disease. Additionally, platelets contribute to the local inflammatory response and may also participate in progenitor cell recruitment.

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