Aortic arterial stiffness associates with carotid intima-media thickness and carotid plaques in younger middle-aged healthy people.

PURPOSE: Aortic stiffness, assessed as estimated aortic pulse wave velocity (aPWV), and carotid intima-media thickness (cIMT) are markers of vascular age, and carotid plaques are a marker of early atherosclerosis. In this cross-sectional study we aimed to investigate the association between aPWV, cIMT and plaques across different age groups and in women and men, in a middle-aged healthy population. MATERIALS AND METHODS: Participants in the 6.5-year follow-up of the VIPVIZA trial who were aged 47, 57 and 67 underwent an oscillometric measurement which estimates aPWV between 2020 and 2023. Carotid ultrasound examinations were also performed. Linear and ordinal regression models were used to investigate how aPWV associates with cIMT and with carotid plaques, for the overall study group and stratified for age groups and sex. RESULTS: A total of 1046 subjects were included in the analyses. Linear associations between aPWV and cIMT (ß = 0.018, 95% CI: 0.006-0.030, p = 0.003), and between aPWV and plaques (OR: 1.19, 95% CI: 1.03-1.38, p = 0.018), were seen in the 57-year-olds. In the 47-year-olds a significant association was seen between aPWV and plaques (OR: 2.98 95% CI: 1.44-6.14, p = 0.003). No significant associations were seen in the 67-year-olds. For women, a significant association between aPWV and cIMT (ß = 0.011, 95% CI: 0.004-0.017, p = 0.002) was shown. CONCLUSION: Estimated aPWV was positively associated with increasing cIMT and the presence of carotid plaques in younger middle-aged individuals, and with cIMT in women, suggesting that measurement of estimated aPWV may improve cardiovascular risk assessment in younger middle-aged individuals and women.Clinical Trial Registration date 8 May 2013: URL: www.clinicaltrials.gov. Unique identifier: NCT01849575.

What is the context? Vascular ageing is a process where the arteries become stiff, leading to impaired function and organ damage. Stiff arteries increase the risk of cardiovascular disease. Aortic pulse wave velocity is a measurement of arterial stiffness and a marker of vascular age. Carotid intima-media thickness and carotid plaque presence are other markers of vascular age and early atherosclerosis. There are limited data on the association between aortic pulse wave velocity, carotid intima-media thickness and carotid plaques.What is new? We measured estimated aortic pulse wave velocity using an oscillometric device and performed carotid ultrasound examinations for assessment of carotid intima-media thickness and carotid plaques in healthy middle-aged individuals across three different age groups. The association between aortic pulse wave velocity, carotid intima-media thickness and carotid plaques was examined in the different age groups and in women and men separately.What is the impact? Estimated aortic pulse wave velocity was associated with carotid intima-media thickness and carotid plaques in younger middle-aged individuals and with carotid intima-media thickness in women. Suggesting that for these groups ­ healthy younger middle-aged people, and especially women ­ measurement of estimated aortic pulse wave velocity could improve evaluation of cardiovascular risk.

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 behaviour of these substances within the arterial wall is described by convection-diffusion-reaction equations, while the arterial wall itself is modelled 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.

Simulation of plaque formation in a realistic geometry of a human aorta: effects of endothelial layer properties, heart rate, and hypertension.

Nowadays, cardiovascular diseases are the most common cause of death worldwide. Besides, atherosclerosis is a cardiovascular disease that occurs with persistent narrowing of arteries, especially medium and large-sized arteries. Atherosclerosis begins with a local elevation in the permeability of the arterial wall as a result of endothelial inflammation. Subsequently, excess LDL permeates into the arterial wall. Then, through several chemical responses and reactions, foam cells are produced. These foam cells serve as a crucial indicator for assessing the development of atherosclerosis within the arteries. In this study, the effect of endothelial layer modeling, heart rate (HR) and hypertension on the foam cell accumulation is numerically investigated in a patient-specific geometry of the human thoracic aorta. Navier-Stokes, Darcy, and mass transfer equations are used to obtain the velocity and concentration field within the domain. Regarding the dependence of endothelial cell properties on time-averaged wall shear stress, it is observed that foam cells are mainly concentrated in the outer curvature of the aortic arch, downstream of the left subclavian artery. However, considering oscillatory-shear-rate as the determinant of endothelial cell properties leads to the accumulation of foam cells in the inner curvature of the descending aorta. Regarding the HR, with the increase of HR, the volume average concentration of the foam cell decreases. However, there is no substantial difference between the cases of different HRs. Moreover, foam cell concentration significantly increases in the hypertension case. This result implies that a slight increase in the blood pressure may induce irreparable problems in the circulatory system.

Impact of geometric and hemodynamic changes on a mechanobiological model of atherosclerosis.

BACKGROUND AND OBJECTIVE: In this work, the analysis of the importance of hemodynamic updates on a mechanobiological model of atheroma plaque formation is proposed. METHODS: For that, we use an idealized and axisymmetric model of carotid artery. In addition, the behavior of endothelial cells depending on hemodynamical changes is analyzed too. A total of three computational simulations are carried out and their results are compared: an uncoupled model and two models that consider the opposite behavior of endothelial cells caused by hemodynamic changes. The model considers transient blood flow using the Navier-Stokes equation. Plasma flow across the endothelium is determined with Darcy's law and the Kedem-Katchalsky equations, considering the three-pore model, which is also employed for the flow of substances across the endothelium. The behavior of the considered substances in the arterial wall is modeled with convection-diffusion-reaction equations, and the arterial wall is modeled as a hyperelastic Yeoh's material. RESULTS: Significant variations are noted in both the morphology and stenosis ratio of the plaques when comparing the uncoupled model to the two models incorporating updates for geometry and hemodynamic stimuli. Besides, the phenomenon of double-stenosis is naturally reproduced in the models that consider both geometric and hemodynamical changes due to plaque growth, whereas it cannot be predicted in the uncoupled model. CONCLUSIONS: The findings indicate that integrating the plaque growth model with geometric and hemodynamic settings is essential in determining the ultimate shape and dimensions of the carotid plaque.

Effect of variability of mechanical properties on the predictive capabilities of vulnerable coronary plaques.

BACKGROUND AND OBJECTIVE: Coronary plaque rupture is a precipitating event responsible for two thirds of myocardial infarctions. Currently, the risk of plaque rupture is computed based on demographic, clinical, and image-based adverse features. However, using these features the absolute event rate per single higher-risk lesion remains low. This work studies the power of a novel framework based on biomechanical markers accounting for material uncertainty to stratify vulnerable and non-vulnerable coronary plaques. METHODS: Virtual histology intravascular ultrasounds from 55 patients, 29 affected by acute coronary syndrome and 26 affected by stable angina pectoris, were included in this study. Two-dimensional vessel cross-sections for finite element modeling (10 sections per plaque) incorporating plaque structure (medial tissue, loose matrix, lipid core and calcification) were reconstructed. A Montecarlo finite element analysis was performed on each section to account for material variability on three biomechanical markers: peak plaque structural stress at diastolic and systolic pressure, and peak plaque stress difference between systolic and diastolic pressures, together with the luminal pressure. Machine learning decision tree classifiers were trained on 75% of the dataset and tested on the remaining 25% with a combination of feature selection techniques. Performance against classification trees based on geometric markers (i.e., luminal, external elastic membrane and plaque areas) was also performed. RESULTS: Our results indicate that the plaque structural stress outperforms the classification capacity of the combined geometric markers only (0.82 vs 0.51 area under curve) when accounting for uncertainty in material parameters. Furthermore, the results suggest that the combination of the peak plaque structural stress at diastolic and systolic pressures with the maximum plaque structural stress difference between systolic and diastolic pressures together with the systolic pressure and the diastolic to systolic pressure gradient is a robust classifier for coronary plaques when the intrinsic variability in material parameters is considered (area under curve equal to [0.91-0.93]). CONCLUSION: In summary, our results emphasize that peak plaque structural stress in combination with the patient's luminal pressure is a potential classifier of plaque vulnerability as it independently considers stress in all directions and incorporates total geometric and compositional features of atherosclerotic plaques.

New Research Could Help Explain Anger's Link to Heart Attacks and Strokes.

This Medical News article discusses a randomized clinical trial that investigated the effects of negative emotions on blood vessel dilation.

Impact of endothelial shear stress on coronary atherosclerotic plaque progression and composition: A meta-analysis and systematic review.

BACKGROUND AND AIMS: Intracoronary pressure gradients and translesional flow patterns have been correlated with coronary plaque progression and lesion destabilization. In this study, we aimed to determine the relationship between endothelial shear stress and plaque progression and to evaluate the effect of shear forces on coronary plaque features. METHODS: A systematic review was conducted in medical on-line databases. Selected were studies including human participants who underwent coronary anatomy assessment with computational fluid dynamics (CFD)-based wall shear stress (WSS) calculation at baseline with anatomical evaluation at follow-up. A total of six studies were included for data extraction and analysis. RESULTS: The meta-analysis encompassed 31'385 arterial segments from 136 patients. Lower translesional WSS values were significantly associated with a reduction in lumen area (mean difference -0.88, 95% CI -1.13 to -0.62), an increase in plaque burden (mean difference 4.32, 95% CI 1.65 to 6.99), and an increase in necrotic core area (mean difference 0.02, 95% CI 0.02 to 0.03) at follow-up imaging. Elevated WSS values were associated with an increase in lumen area (mean difference 0.78, 95% CI 0.34 to 1.21) and a reduction in both fibrofatty (mean difference -0.02, 95% CI -0.03 to -0.01) and fibrous plaque areas (mean difference -0.03, 95% CI -0.03 to -0.03). CONCLUSION: This meta-analysis shows that WSS parameters were related to vulnerable plaque features at follow-up. These results emphasize the impact of endothelial shear forces on coronary plaque growth and composition. Future studies are warranted to evaluate the role of WSS in guiding clinical decision-making.

A parametric study of the effect of 3D plaque shape on local hemodynamics and implications for plaque instability.

The vast majority of heart attacks occur when vulnerable plaques rupture, releasing their lipid content into the blood stream leading to thrombus formation and blockage of a coronary artery. Detection of these unstable plaques before they rupture remains a challenge. Hemodynamic features including wall shear stress (WSS) and wall shear stress gradient (WSSG) near the vulnerable plaque and local inflammation are known to affect plaque instability. In this work, a computational workflow has been developed to enable a comprehensive parametric study detailing the effects of 3D plaque shape on local hemodynamics and their implications for plaque instability. Parameterized geometric 3D plaque models are created within a patient-specific coronary artery tree using a NURBS (non-uniform rational B-splines)-based vascular modeling pipeline. Realistic blood flow features are simulated by using a Navier-Stokes solver within an isogeometric finite-element analysis framework. Near wall hemodynamic quantities such as WSS and WSSG are quantified, and vascular distribution of an inflammatory marker (VCAM-1) is estimated. Results show that proximally skewed eccentric plaques have the most vulnerable combination of high WSS and high positive spatial WSSG, and the presence of multiple lesions increases risk of rupture. The computational tool developed in this work, in conjunction with clinical data, -could help identify surrogate markers of plaque instability, potentially leading to a noninvasive clinical procedure for the detection of vulnerable plaques before rupture.

Pathophysiology and Optimal Treatment of Intracranial Branch Atheromatous Disease.

Intracranial branch atheromatous disease (BAD) is a pathological condition characterized by the occlusion of a relatively large perforating branch (700-800 µm) near the orifice of a parent artery due to atherosclerotic plaque-based thrombus (microatheroma). BAD is refractory to treatment and follows a course of progressive exacerbation, especially motor paralysis. Uniform treatment for common atherothrombotic cerebral infarction or lacunar infarction does not prevent the progressive exacerbation of BAD, and consequently affects functional prognosis. To date, various combinations of treatments have been investigated and proposed to attenuate the worsening symptoms of BAD. However, no therapy with established efficacy is yet available for BAD. Since it is the most difficult condition to treat in the area of cerebral infarction, the establishment of optimal treatment methods for BAD is keenly awaited. This review presents an overview of the acute treatments available for BAD and discusses the prospects for optimal treatment.

Association of Coronary Plaque With Low-Density Lipoprotein Cholesterol Levels and Rates of Cardiovascular Disease Events Among Symptomatic Adults.

Importance: Atherosclerosis burden and coronary artery calcium (CAC) are associated with the risk for atherosclerotic cardiovascular disease (ASCVD) events, with absence of plaque and CAC indicating low risk. Whether this is true in patients with elevated levels of low-density lipoprotein cholesterol (LDL-C) is not known. Specifically, a high prevalence of noncalcified plaque might signal high risk. Objective: To determine the prevalence of noncalcified and calcified plaque in symptomatic adults and assess its association with cardiovascular events across the LDL-C spectrum. Design, Setting, and Participants: This cohort study included symptomatic patients undergoing coronary computed tomographic angiography from January 1, 2008, to December 31, 2017, from the seminational Western Denmark Heart Registry. Follow-up was completed on July 6, 2018. Data were analyzed from April 2 to December 2, 2021. Exposures: Prevalence of calcified and noncalcified plaque according to LDL-C strata of less than 77, 77 to 112, 113 to 154, 155 to 189, and at least 190 mg/dL. Severity of coronary artery disease was categorized using CAC scores of 0, 1 to 99, and ≥100, where higher numbers indicate greater CAC burden. Main Outcomes and Measures: Atherosclerotic cardiovascular disease events (myocardial infarction and stroke) and death. Results: A total of 23 143 patients with a median age of 58 (IQR, 50-65) years (12 857 [55.6%] women) were included in the analysis. During median follow-up of 4.2 (IQR, 2.3-6.1) years, 1029 ASCVD and death events occurred. Across all LDL-C strata, absence of CAC was a prevalent finding (ranging from 438 of 948 [46.2%] in patients with LDL-C levels of at least 190 mg/dL to 4370 of 7964 [54.9%] in patients with LDL-C levels of 77-112 mg/dL) and associated with no detectable plaque in most patients, ranging from 338 of 438 (77.2%) in those with LDL-C levels of at least 190 mg/dL to 1067 of 1204 (88.6%) in those with LDL-C levels of less than 77 mg/dL. In all LDL-C groups, absence of CAC was associated with low rates of ASCVD and death (6.3 [95% CI, 5.6-7.0] per 1000 person-years), with increasing rates in patients with CAC scores of 1 to 99 (11.1 [95% CI, 10.0-12.5] per 1000 person-years) and CAC scores of at least 100 (21.9 [95% CI, 19.9-24.4] per 1000 person-years). Among those with CAC scores of 0, the event rate per 1000 person-years was 6.3 (95% CI, 5.6-7.0) in the overall population compared with 6.9 (95% CI, 4.0-11.9) in those with LDL-C levels of at least 190 mg/dL. Across all LDL-C strata, rates were similar and low in those with CAC scores of 0, regardless of whether they had no plaque or purely noncalcified plaque. Conclusions and Relevance: The findings of this cohort study suggest that in symptomatic patients with severely elevated LDL-C levels of at least 190 mg/dL who are universally considered to be at high risk by guidelines, absence of calcified and noncalcified plaque on coronary computed tomographic angiography was associated with low risk for ASCVD events. These results further suggest that atherosclerosis burden, including CAC, can be used to individualize treatment intensity in patients with severely elevated LDL-C levels.

Normalized Subendocardial Myocardial Attenuation on Coronary Computed Tomography Angiography Predicts Postoperative Adverse Cardiovascular Events: Coronary CTA VISION Substudy.

BACKGROUND: Abnormalities in computed tomography myocardial perfusion has been associated with coronary artery disease and major adverse cardiovascular events (MACE). We sought to investigate if subendocardial attenuation using coronary computed tomography angiography predicts MACE 30 days postelective noncardiac surgery. METHODS: Using a 17-segment model, coronary computed tomography angiography images were analyzed for subendocardial and transmural attenuation and the corresponding blood pool. The segment with the lowest subendocardial attenuation and transmural attenuation were normalized to the segment with the highest subendocardial and transmural attenuation, respectively (SUBnormalized, and TRANSnormalized, respectively). We evaluated the independent and incremental value of myocardial attenuation to predict the composite of cardiovascular death or nonfatal myocardial infarction. RESULTS: Of a total of 995 coronary CTA VISION (Coronary Computed Tomographic Angiography and Vascular Events in Noncardiac Surgery Patients Cohort Evaluation Study) patients, 735 had available images and complete data for these analyses. Among these patients, 60 had MACE. Based on Revised Cardiovascular Risk Index, 257, 302, 138, and 38 patients had scores of 0, 1, 2, and ≥3, respectively. On coronary computed tomography angiography, 75 patients had normal coronary arteries, 297 patients had nonobstructive coronary artery disease, 264 patients had obstructive disease, and 99 patients had extensive obstructive coronary artery disease. SUBnormalized was an independent and incremental predictor of events in the model that included Revised Cardiovascular Risk Index and coronary artery disease severity. Compared with patients in the highest tertile of SUBnormalized, patients in the second and first tertiles had an increased hazards ratio for events (2.23 [95% CI, 1.091-4.551] and 2.36 [95% CI, 1.16-4.81], respectively). TRANSnormalized, as a continuous variable, was also found to be a predictor of MACE (P=0.027). CONCLUSIONS: Our study demonstrates that SUBnormalized and TRANSnormalized are independent and incremental predictors of MACE 30 days after elective noncardiac surgery. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01635309.

Effect of Calcification Based on Computer-Aided System on CT-Fractional Flow Reserve in Diagnosis of Coronary Artery Lesion.

This study was to analyze the diagnostic value of coronary computed tomography angiography (CCTA) and fractional flow reserve (FFR) based on computer-aided diagnosis (CAD) system for coronary lesions and the possible impact of calcification. 80 patients who underwent CCTA and FFR examination in hospital were selected as the subjects. The FFR value of 0.8 was used as the dividing line and divided into the ischemic group (FFR ≤ 0.8) and nonischemic group (FFR > 0.8). The basic data and imaging characteristics of patients were analyzed. The maximum diameter stenosis rate (MDS %), maximum area stenosis rate (MAS %), and napkin ring sign (NRS) in the ischemic group were significantly lower than those in the nonischemic group (P < 0.05). Remodeling index (RI) and eccentric index (EI) compared with the nonischemic group had no significant difference (P > 0.05). The total plaque volume (TPV), total plaque burden (TPB), calcified plaque volume (CPV), lipid plaque volume (LPV), and lipid plaque burden (LPB) in the ischemic group were significantly different from those in the non-ischemic group (P < 0.05). MAS % had the largest area under curve (AUC) for the diagnosis of coronary myocardial ischemia (0.74), followed by MDS % (0.69) and LPV (0.68). CT-FFR had high diagnostic sensitivity, specificity, accuracy, truncation value, and AUC area data for patients in the ischemic group and nonischemic group. The diagnostic sensitivity, specificity, accuracy, cutoff value, and AUC area data of CT-FFR were higher in the ischemic group (89.93%, 92.07%, 95.84%, 60.51%, 0.932) and nonischemic group (93.75%, 90.88%, 96.24%, 58.22%, 0.944), but there were no significant differences between the two groups (P > 0.05). In summary, CT-FFR based on CAD system has high accuracy in evaluating myocardial ischemia caused by coronary artery stenosis, and within a certain range of calcification scores, calcification does not affect the diagnostic accuracy of CT-FFR.

Predictive mouse model reflects distinct stages of human atheroma in a single carotid artery.

Identification of patients with high-risk asymptomatic atherosclerotic plaques remains an elusive but essential step in preventing stroke. However, there is a lack of animal model that provides a reproducible method to predict where, when and what types of plaque formation, which fulfils the American Heart Association (AHA) histological classification of human plaques. We have developed a predictive mouse model that reflects different stages of human plaques in a single carotid artery by means of shear-stress modifying cuff. Validated with over 30000 histological sections, the model generates a specific pattern of plaques with different risk levels along the same artery depending on their position relative to the cuff. The further upstream of the cuff-implanted artery, the lower the magnitude of shear stress, the more unstable the plaques of higher grade according to AHA classification; with characteristics including greater degree of vascular remodeling, plaque size, plaque vulnerability and inflammation, resulting in higher risk plaques. By weeks 20 and 30, this model achieved 80% and near 100% accuracy respectively, in predicting precisely where, when and what stages/AHA types of plaques develop along the same carotid artery. This model can generate clinically-relevant plaques with varying phenotypes fulfilling AHA classification and risk levels, in specific locations of the single artery with near 100% accuracy of prediction. The model offers a promising tool for development of diagnostic tools to target high-risk plaques, increasing accuracy in predicting which individual patients may require surgical intervention to prevent stroke, paving the way for personalized management of carotid atherosclerotic disease.

Prolonged sitting time links to subclinical atherosclerosis.

BACKGROUND: This study investigates the association between daily sitting time and subclinical atherosclerosis by using coronary computed tomography angiography (CCTA). METHODS: The study enrolled 203 subjects (age 57.6 ± 8.8 years) who underwent CCTA at annual medical checkups. Sitting time was categorized as < 5 hours/day (short), 5 to 9 hours/day (moderate) and ≥10 hours/d (long). We analyzed the coronary calcium score, plaque characteristics, and severity of coronary artery stenosis, including the segment involvement score (SIS) and segment stenosis score (SSS). RESULTS: Subjects with longer sitting times tended to be male gender and have lower levels of high-density lipoprotein cholesterol (p for trend < 0.05). In addition, those with longer sitting time had higher SIS (1.2 ± 1.5 vs. 1.6 ± 2.1 vs. 2.3 ± 2.0 for short, moderate, and long sitting time, respectively) (p for trend = 0.015) and SSS (1.4 ± 2.0 vs. 1.9 ± 2.7 vs. 2.7 ± 2.6) (p for trend = 0.015), suggesting longer sitting time-correlated with the severity of coronary atherosclerosis. When considering the coronary plaque patterns, subjects with shorter sitting time (<5 hours/d) tended to have more calcified plaque and subjects with longer sitting time (≥10 hours/d) had more mixed plaque (p for trend = 0.018). After adjusting for age, gender, comorbidities, body mass index, and lipid profiles, increased sitting time was independently associated with the presence of mixed plaque, suggesting longer sitting time may be associated with higher risk of the formation of vulnerable plaque. CONCLUSION: Longer sitting time was linked to the severity of subclinical atherosclerosis and the presence of high-risk vulnerable plaque in the general population.

The Key Genes Underlying Pathophysiology Association between Plaque Instability and Progression of Myocardial Infarction.

Young patients with type 2 diabetes and myocardial infarction (MI) have higher long-term all-cause and cardiovascular mortality. In addition, the observed increased, mildly abnormal baseline lipid levels, but not lipid variability, are associated with an increased risk of atherosclerotic cardiovascular disease events, particularly MI. This study investigated differentially expressed genes (DEGs), which might be potential targets for young patients with MI and a high-fat diet (HFD). GSE114695 and GSE69187 were downloaded and processed using the limma package. A Venn diagram was applied to identify the same DEGs, and further pathway analysis was performed using Metascape. Protein-protein interaction (PPI) network analysis was then applied, and the hub genes were screened out. Pivotal miRNAs were predicted and validated using the miRNA dataset in GSE114695. To investigate the cardiac function of the screened genes, an MI mouse model, echocardiogram, and ELISA of hub genes were applied, and a correlation analysis was also performed. From aged mice fed HFD, 138 DEGs were extracted. From aged mice fed with chow, 227 DEGs were extracted. Pathway enrichment analysis revealed that DEGs in aging mice fed HFD were enriched in lipid transport and lipid biosynthetic process 1 d after MI and in the MAPK signaling pathway at 1 w after MI, suggesting that HFD has less effect on aging with MI. A total of 148 DEGs were extracted from the intersection between plaques fed with HFD and chow in young mice and MI_1d, respectively, which demonstrated increased inflammatory and adaptive immune responses, in addition to myeloid leukocyte activation. A total of 183 DEGs were screened out between plaques fed with HFD vs. chow in young mice and MI_1w, respectively, which were mainly enriched in inflammatory response, cytokine production, and myeloid leukocyte activation. After validation, PAK3, CD44, CD5, SOCS3, VAV1, and PIK3CD were demonstrated to be negatively correlated with LVEF; however, P2RY1 was demonstrated to be positively correlated. This study demonstrated that the screened hub genes may be therapeutic targets for treating STEMI patients and preventing MI recurrence, especially in young MI patients with HFD or diabetes.

Impact of H-Type Hypertension on Pericarotid Adipose Tissue and Plaque Characteristics Based on Computed Tomography (CT) Angiography: A Propensity Score Matching Study.

BACKGROUND We analyzed the correlation among the inflammatory changes in pericarotid adipose tissue (PCAT), plaque characteristics, and H-type hypertension on CT angiography (CTA) and explored the utility of CTA in the prevention and treatment of carotid atherosclerosis. MATERIAL AND METHODS A total of 135 patients who underwent head and neck CTA to investigate carotid artery atherosclerosis were retrospectively analyzed. The plaque characteristic parameters (plaque burden and remodeling index), PCAT attenuation value, and net enhancement value around the carotid artery, where the plaques were located, were recorded, and confounding factors were matched by propensity score analysis. A paired t test was used to compare the differences in fat tissue inflammatory changes and plaque characteristic parameters between the 2 groups, and logistic regression analysis was used to evaluate the relationship between plaque characteristics and the attenuation values and net enhancement values of PCAT. The correlation coefficient was calculated between type H hypertension and plaque risk grade. RESULTS The results of the experiment indicate that PCAT attenuation values and net enhancement values gradually increased as the degree of hypertension increased. Compared with those of patients in the normal Hcy group, these values increased more clearly in patients with high Hcy (HHcy) (r=0.641, P<0.001, r=0.581, P<0.001), although, regardless of whether the Hcy value increased, there were significant differences between the groups. However, this effect was more pronounced in patients with H-type hypertension. Logistic regression analysis of risk factors for carotid atherosclerotic plaque suggests that Hcy (OR=1.391, 95% CI 1.146-1.689, P=0.001), PCAT attenuation values (OR=1.212, 95% CI 1.074-1.367, P=0.002), and net enhancement values (OR=1.201, 95% CI 1.042-1.383, P=0.011) were independent risk factors for plaque vulnerability. CONCLUSIONS Our results suggest that H-type hypertension is significantly associated with PCAT attenuation and net enhancement and that PCAT net enhancement values are useful in predicting plaque risk as attenuation.

Inflammation Drives Stiffness Mediated Uptake of Lipoproteins in Primary Human Macrophages and Foam Cell Proliferation.

Macrophage to foam cell transition and their accumulation in the arterial intima are the key events that trigger atherosclerosis, a multifactorial inflammatory disease. Previous studies have linked arterial stiffness and cardiovascular disease and have highlighted the use of arterial stiffness as a potential early-stage marker. Yet the relationship between arterial stiffness and atherosclerosis in terms of macrophage function is poorly understood. Thus, it is pertinent to understand the mechanobiology of macrophages to clarify their role in plaque advancement. We explore how substrate stiffness affects proliferation of macrophages and foam cells, traction forces exerted by macrophages and uptake of native and oxidized low-density lipoproteins. We demonstrate that stiffness influences foam cell proliferation under both naïve and inflammatory conditions. Naïve foam cells proliferated faster on the 4 kPa polyacrylamide gel and glass whereas under inflammatory conditions, maximum proliferation was recorded on glass. Macrophage and foam cell traction forces were positively correlated to the substrate stiffness. Furthermore, the influence of stiffness was demonstrated on the uptake of lipoproteins on macrophages treated with lipopolysaccharide + interferon gamma. Cells on softer 1 kPa substrates had a significantly higher uptake of low-density lipoproteins and oxidized low-density lipoproteins compared to stiffer substrates. The results herein indicate that macrophage function is modulated by stiffness and help better understand ways in which macrophages and foam cells could contribute to the development and progression of atherosclerotic plaque.