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Our previous study finds that exosomal microRNA (miR)-186-5p promotes viability and invasion of vascular smooth muscle cells to accelerate atherosclerosis via inactivating phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin pathway. Subsequently, this study aimed to identify the linkage of serum exosomal miR-186-5p with clinical features and major adverse cardiovascular events (MACE) in coronary heart disease (CHD) patients. Serum exosomal miR-186-5p was quantified in 175 CHD patients and 50 healthy controls (HCs) via reverse transcription quantitative polymerase chain reaction. Our study revealed that serum exosomal miR-186-5p was enhanced in CHD patients vs. HCs (P < 0.001). In CHD patients, serum exosomal miR-186-5p was positively correlated with total cholesterol (P = 0.002) and low-density lipoprotein cholesterol (P = 0.003). Elevated serum exosomal miR-186-5p was linked with increased Gensini score (P = 0.028) and stenosis degree categorized by the Gensini score (P = 0.018). Regarding MACE, the 1-year and 2-year accumulating MACE rate was 6.6% and 15.6%, respectively. Serum exosomal miR-186-5p was elevated in CHD patients with MACE vs. those without (P = 0.042). By Kaplan-Meier curves and log-rank analyses, serum exosomal miR-186-5p > 1.000 (P = 0.404) and > 1.610 (P = 0.328) was not related to accumulating MACE. While serum exosomal miR-186-5p > 3.390 exhibited a correlative trend with increased accumulating MACE, but not achieving statistical significance (P = 0.071). The 1-year and 2-year accumulating MACE rate of patients with serum exosomal miR-186-5p > 3.390 was 11.5% and 21.5%, respectively; while the rate was 3.3% and 11.5% in patients with serum exosomal miR-186-5p ≤ 3.390, accordingly. Conclusively, serum exosomal miR-186-5p positively associates with lipid level, coronary stenosis degree, and the risk of MACE in CHD patients.

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Soluble low-density lipoprotein receptor-related protein-1 (sLRP-1) plays a crucial role in facilitating inflammation, lipid accumulation, and atherosclerosis, and the latter factors are involved in the pathology of cardiovascular diseases. This study aimed to explore the ability of plasma sLRP-1 for reflecting stenosis degree in acute coronary syndrome (ACS) patients. sLRP-1 was detected from plasma by enzyme-linked immunosorbent assay in 169 ACS patients and 77 non-ACS subjects (as controls) after admission. Our study illustrated that sLRP-1 was increased in ACS patients versus controls (P < 0.001). Meanwhile, sLRP-1 was positively correlated with body mass index (P = 0.021), white blood cells (P = 0.009), neutrophils (P = 0.002), cardiac troponin I (P = 0.009), and brain natriuretic peptide (P = 0.008) in ACS patients. Notably, sLRP-1 was positively associated with the Gensini score (P = 0.002) and Gensini score stratified stenosis severity (P = 0.004) in ACS patients. After adjustment, sLRP-1 [odds ratio (OR) = 1.333, P = 0.045] independently estimated a higher risk of moderate-severe stenosis, so did numbers of coronary artery lesions (OR = 2.869, P = 0.001), but ejection fraction forecasted a lower risk (OR = 0.880, P = 0.012). Interestingly, a combination of sLRP-1, ejection fraction, and numbers of coronary artery lesions exhibited a good ability to estimate moderate-severe stenosis risk with an area under the curve (95% confidence interval) of 0.845 (0.783-0.906). In summary, increased plasma sLRP-1 represents an aggravated inflammation, impaired cardiac function, and especially a higher stenosis severity in ACS patients.

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Cell division control 42 (CDC42) regulates blood lipids, atherosclerosis, T cell differentiation and inflammation, which is involved in the process of coronary heart disease (CHD). This study aimed to evaluate the CDC42 level and its correlation with clinical features, the T-helper 17 (Th17)/regulatory-T (Treg) cell ratio and prognosis in CHD patients. In total, 210 CHD patients, 20 healthy controls and 20 disease controls were enrolled. Serum CDC42 levels of all participants were measured by enzyme-linked immunosorbent assay. In CHD patients, Th17 and Treg cells were discovered by flow cytometry; CHD patients were followed-up for a median of 16.9 months (range of 2.5-38.2 months). CDC42 level was lowest in CHD patients (median (interquartile range (IQR)): 402.5 (287.3-599.0) pg/mL), moderate in disease controls (median (IQR): 543.5 (413.0-676.3) pg/mL) and highest in healthy controls (median (IQR): 668.0 (506.5-841.3) pg/mL) (p < .001). Moreover, in CHD patients, lower CDC42 level was related to more prevalent diabetes mellitus (p = .021), and higher levels of C-reactive protein (p = .001), Gensini score (p = .006), Th17 cells (p = .001) and Th17/Treg ratio (p < .001) but was associated with lower Treg cells (p = .018). Furthermore, CDC42 low level [below the median level (402.5 pg/mL) of CDC42 in CHD patients] was correlated with higher accumulating major adverse cardiovascular event (MACE) risk (p = .029), while no correlation was found between the quartile of CDC42 level and accumulating MACE risk in CHD patients (p = .102). The serum CDC42 level is decreased and its low level is related to higher Th17/Treg ratio and increased accumulating MACE risk in CHD patients.

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OBJECTIVE: Long non-coding RNA activated by DNA damage (lnc-NORAD) modulates inflammation, lipid level, and atherosclerosis in various cardiovascular diseases. This study intended to investigate the dysregulated expression of lnc-NORAD, and its linkage with clinical characteristics, inflammatory cytokines, and accumulating major adverse cardiovascular events (MACE) in coronary heart disease (CHD) patients. METHODS: Totally, 160 CHD patients, 30 disease controls (DCs), and 30 healthy controls (HCs) were included. The reverse transcription-quantitative polymerase chain reaction was used to detect lnc-NORAD expression in peripheral blood mononuclear cell samples from all participants. Enzyme-linked immunosorbent assay was applied to detect proinflammatory cytokines and adhesion molecules in CHD patients. Then, MACE was recorded during a median follow-up of 12 (range: 1.0-27.0) months. RESULTS: Lnc-NORAD was highest in CHD patients, followed by DCs, and lowest in HCs (p < 0.001). In CHD patients, lnc-NORAD was positively linked with Gensini score (p = 0.001). Meanwhile, lnc-NORAD was positively linked to C-reactive protein (p = 0.023), tumor necrosis factor-alpha (p = 0.016), interleukin (IL)-6 (p = 0.003), IL-8 (P = 0.018), and IL-17A (p = 0.029). No relation of lnc-NORAD with vascular cell adhesion molecule-1 (p = 0.094) and intercellular adhesion molecule-1 (p = 0.060) was found. Furthermore, lnc-NORAD was positively related to total cholesterol (p = 0.014) and low-density lipoprotein cholesterol (p = 0.004), whereas lnc-NORAD was not linked to triglyceride (p = 0.103) and high-density lipoprotein cholesterol (p = 0.533). However, lnc-NORAD (high vs. low), and its higher quartiles were both not linked to accumulating MACE rate (p > 0.05). CONCLUSION: Increased lnc-NORAD is linked with aggravated stenosis degree, inflammation status, and blood lipid in CHD patients. However, further validation is required.

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BACKGROUND: MicroRNA-34a (miR-34a) plays an essential role in regulating blood lipid, inflammation, cell adhesion molecules, and atherosclerosis, the latter factors are closely involved in the etiology of coronary heart disease (CHD). However, the clinical value of miR-34a in CHD patients' management is rarely reported. Hence, this study aimed to assess the correlation of miR-34a with disease risk, blood lipid, coronary artery stenosis, inflammatory cytokines, and cell adhesion molecules of CHD. METHODS: A total of 203 CHD patients and 100 controls were recruited in this study, then their plasma samples were collected to detect the miR-34a by reverse transcription quantitative polymerase chain reaction. Furthermore, serum samples from CHD patients were obtained for inflammatory cytokines and cell adhesion molecule measurement by enzyme-linked immunosorbent assay. RESULTS: MiR-34a was elevated in CHD patients compared to controls (p < 0.001) and it disclosed a good diagnostic value of CHD (area under curve: 0.899, 95% confidence interval: 0.865-0.934). Besides, miR-34a positively correlated with triglyceride (p < 0.001), total cholesterol (p = 0.022) and low-density lipoprotein cholesterol (p = 0.004), but not with high-density lipoprotein cholesterol (p = 0.110) in CHD patients. Moreover, miR-34a associated with Gensini score in CHD patients (p < 0.001). As to inflammation-related indexes and cell adhesion molecules, MiR-34a expression was positively linked with C-reactive protein (p < 0.001), tumor necrosis factor alpha (p = 0.005), interleukin (IL)-1ß (p = 0.020), IL-17A (p < 0.001), vascular cell adhesion molecule-1 (p < 0.001), and intercellular adhesion molecule-1 (p = 0.010) in CHD patients, but not with IL-6 (p = 0.118) and IL-10 (p = 0.054). CONCLUSION: MiR-34a might serve as a biomarker in assistance of diagnosis and management of CHD.

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BACKGROUND: Long noncoding RNA urothelial cancer-associated 1 (lnc-UCA1) targets microRNA-26a (miR-26a) and microRNA-195 (miR-195) to participate in coronary heart disease (CHD) progression via regulation of vascular smooth muscle cell and microvascular endothelial cell viability and mobility. Therefore, this study set out to further explore the relationship between lnc-UCA1 and miR-26a and miR-195, along with their roles in the management of patients with CHD. METHODS: One hundred and thirty-six CHD patients and 70 age-/gender-matched controls were recruited in this case-control study. Their peripheral blood mononuclear cell samples were collected for lnc-UCA1, miR-26a, and miR-195 measurement. Furthermore, serum samples from CHD patients were obtained for inflammatory cytokines and cell adhesion molecules measurement. The Gensini score was used to evaluate the stenosis severity in CHD patients. RESULTS: Lnc-UCA1 expression tend to be increased, while miR-26a and miR-195 expressions were reduced in patients with CHD compared to that of controls (all p < 0.001). In CHD patients, lnc-UCA1 was negatively correlated with miR-26a (p < 0.001) and miR-195 (p = 0.014). Besides, lnc-UCA1 was positively correlated with Gensini score (p < 0.001), total cholesterol (p = 0.019), low-density lipoprotein cholesterol (p = 0.002), and C-reactive protein (p < 0.001), while miR-26a (p < 0.001) and miR-195 (p = 0.002) were negatively correlated with Gensini score. What's more, lnc-UCA1 was positively correlated with tumor necrosis factor (TNF)-α (p = 0.004), interleukin (IL)-1ß (p = 0.041), vascular cell adhesion molecule-1 (VCAM-1) (p = 0.010), and intercellular adhesion molecule-1 (ICAM-1) (p < 0.001). While miR-26a was negatively correlated with some of the individual inflammatory cytokines and cell adhesion molecules. CONCLUSION: Lnc-UCA1, miR-26a, and miR-195 may serve as potential biomarkers for CHD management.

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BACKGROUND: Cell division cycle 42 (CDC42) regulates macrophage polarization, vascular inflammation, atherosclerosis progression, and modifies differentiation of T helper (Th) cells, while its potential as a biomarker in coronary heart disease (CHD) patients is still lacking. This study aimed to evaluate CDC42 expression, its correlation with Th1, Th2, and Th17 cells, adhesion molecules, and biochemical indexes in CHD patients. METHODS: One hundred two CHD patients and 50 controls were enrolled. CDC42 expression in peripheral blood mononuclear cells was assessed by reverse transcription quantitative polymerase chain reaction in all participants. In CHD patients, Th1, Th2, and Th17 cells were detected by flow cytometric analysis; meanwhile, serum levels of inflammatory cytokines and adhesion molecules were detected by enzyme-linked immunosorbent assay. RESULTS: CDC42 was lower in CHD patients (median (interquartile range (IQR)) = 0.431 (0.304-0.722)) than in controls (median (IQR) = 0.985 (0.572-1.760)) (p < 0.001). CDC42 was positively associated with Th2 cells (p = 0.016) and interleukin (IL)-10 (p = 0.034), but negatively correlated with Th17 cells (p < 0.001) and IL-17A (p < 0.001) in CHD patients. However, no association was found in CDC42 with Th1 cells (p = 0.199) or interferon-γ (p = 0.367) in CHD patients. Besides, CDC42 was negatively correlated with vascular cell adhesion molecule-1 (p = 0.013) and intercellular cell adhesion molecule-1 (p = 0.001) in CHD patients. Additionally, CDC42 negatively associated with C-reactive protein (p < 0.001), Gensini score (p < 0.001), total cholesterol (p = 0.039), and low-density lipoprotein cholesterol (p = 0.014), but not with other biochemical indexes (p > 0.05) in CHD patients. CONCLUSION: CDC42 correlates with Th2 cells, Th17 cells, and adhesion molecules, also reflects inflammation, coronary stenosis degree, and cholesterol level in CHD patients.

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Digital subtraction angiography (DSA) is considered the reference method for the assessment of carotid artery stenosis; however, the procedure is invasive and accompanied by ionizing radiation. Velocity estimation with duplex ultrasound (DUS) is widely used for carotid artery stenosis assessment since no radiation or intravenous contrast is required; however, the method is angle-dependent. Vector concentration (VC) is a parameter for flow complexity assessment derived from the angle independent ultrasound method vector flow imaging (VFI), and VC has shown to correlate strongly with stenosis degree. The aim of this study was to compare VC estimates and DUS estimated peak-systolic (PSV) and end-diastolic velocities (EDV) for carotid artery stenosis patients, with the stenosis degree obtained with DSA. Eleven patients with symptomatic carotid artery stenosis were examined with DUS, VFI, and DSA before and after stent treatment. Compared to DSA, VC showed a strong correlation (r = -0.79, p < 0.001), while PSV (r = 0.68, p = 0.002) and EDV (r = 0.51, p = 0.048) obtained with DUS showed a moderate correlation. VFI using VC calculations may be a useful ultrasound method for carotid artery stenosis and stent patency assessment.

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BACKGROUND AND OBJECTIVE: Nanoparticle-mediated targeted drug delivery is a promising option for treatment of atherosclerosis. However, the drug targeting may be affected by multiple factors. Considerable attentions have been focused on the influences of external factors, e.g., magnetic field, drug-loaded particle, but internal factors, e.g., plaque morphology (stenosis degree and shoulder length), have not received any attention yet. Therefore, we investigate the impact of plaque morphology on magnetic nanoparticles targeting under the action of an external field. METHOD: Numerical simulation, based on Eulerian-Lagrangian coupled Fluid-Solid Interaction, is performed in ANSYS Workbench platform. Blood flow is solved by Navier-Stokes equation, particles are tracked by discrete phase model, and the incorporated effect is obtained by two-way method. Plaques with varying stenosis degrees and shoulder lengths are acquired by manually modifying the geometry of patient-specific. The quantified variables include targeted delivery efficiency (deposition+adhesive strength) of particles and plaque injury characterized by temporal-spatial averaged shear stress (TAWSS¯) during the process of drug transport, in which the critical deposition velocity is determined by plaques and particles, the DEFINE_DPM_BC and User Defined Memory are employed to evaluate whether the particles are deposited, and to store the total number and the adhesive strength of particles deposited on the plaque. RESULTS: Results signify that, with an increment of plaque stenosis degree, the deposition of particle and the adhesive strength between particle and plaque decrease, while the TAWSS¯ increases. Furthermore, for the same stenosis degree, with the increase of plaque shoulder length, the deposition and the adhesive strength of particle increase, and the TAWSS¯ decreases. CONCLUSIONS: Results demonstrates that the plaque with smaller stenosis degree or longer shoulder length may achieve a better treatment effect in view of the higher targeted delivery efficiency of particles and the lighter shear damage to plaque itself during the process of drug transport.

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Correlation of cathepsin S with coronary stenosis degree, carotid thickness, blood pressure, glucose and lipid metabolism, and vascular endothelial function in patients with atherosclerosis was investigated. Data from 120 patients with increased cathepsin S levels (increased group) and 120 subjects with normal cathepsin S levels (normal group) were retrospectively analyzed. The serum cathepsin S level and Gensini score were compared between the healthy subjects and patients with coronary atherosclerotic heart disease, and the correlation between serum cathepsin S level and Gensini score was analyzed. The carotid thickness, mean arterial pressure, and indexes related to glucose and lipid metabolism, as well as vascular endothelial function were compared between the two groups. The correlation of the serum cathepsin S level with carotid intima-media thickness (IMT), mean arterial pressure, fasting blood glucose, total cholesterol (TC) and nitric oxide (NO) was also investigated. Patients with multi-vessel coronary artery disease (CAD) had higher serum cathepsin S level than those with double-vessel and single-vessel disease, and higher level than that of healthy subjects. The Gensini score of patients with multi-vessel CAD was higher than that of patients with double-vessel and single-vessel disease, as well as that of healthy subjects. The serum cathepsin S level was positively correlated with the Gensini score. Patients with increased cathepsin S level had greater IMT, higher mean arterial pressure, fasting blood glucose, fasting insulin (FINS), triglyceride (TG), TC, and endothelin-1 (ET-1), however, lower NO level than those of healthy subjects. The serum cathepsin S level was positively correlated with IMT, mean arterial pressure, fasting blood glucose, and TC, however, it was negatively correlated with the NO level. In conclusion, as the serum cathepsin S level is elevated, the coronary stenosis is aggravated, the carotid thickness and blood pressure are increased, and the glucose and lipid metabolism, as well as vascular endothelial function are significantly abnormal.

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This study examined the application of 64-slice spiral double-low computed tomography (CT) to evaluate the degree of coronary artery stenosis. We examined 45 patients with coronary heart disease by 64-slice spiral double-low CT and coronary angiography (CAG) to determine CT accuracy in evaluating coronary artery stenosis. Imaging analysis from 64-slice spiral double-low CT identified 199 segments with coronary stenosis from 45 patients, including 46 segments with mild stenosis, 38 with moderate stenosis and 115 with severe stenosis or artery occlusion. CT analysis agreed with CAG on the identification of the degree of stenosis in 122 segments, with an overall accuracy of 61.3%. The accuracy for serious stenosis or occlusion was the highest at 69.6%. We also found a strong correlation between coronary plaque compositions and the degree of stenosis. Correspondence analysis showed that the presence of soft plaques closely correlated with severe stenosis, whereas mixed plaques closely correlated with moderate stenosis. Overall, 64-slice spiral double-low CT imaging can effectively assess the degree of coronary artery stenosis in patients with coronary heart disease and accurately detect plaque composition. Thus, 64-slice spiral double-low CT imaging can predict the risk of coronary heart disease and the degree of coronary artery stenosis, which is helpful for early diagnosis and treatment of coronary heart disease.

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OBJECT The progression of arterial stenosis in patients with moyamoya disease (MMD) has variable courses and an unclear mechanism. The authors hypothesized that elevated wall shear stress (WSS) at the terminal internal carotid artery (ICA) and proximal middle cerebral artery (MCA) may facilitate MMD progression. They indirectly evaluated the relative magnitude of WSS (WSS value [WSSV]) with MR angiography (MRA) and transcranial Doppler to determine its predictive value for stenosis progression (SP) and the development of vascular complications. METHODS Thirty-one medically treated patients (58 hemispheres and 95 nonoccluded vessels) were analyzed with serial MRA (median follow-up 23 months). The parameters studied were SP, SP rates (SPRs) for individual ICAs/MCAs, and their mean values from the ipsilateral hemispheres as mean SP (MSP) and MSP rates (MSPRs). Significant progression was defined as decrements of ≥ 20% for SP and MSP and ≥ 10%/year for SPR and MSPR. The development of vascular complications in relevant hemispheres was also recorded. The WSSV (dyne/cm(2)) was defined as the shear rate multiplied by blood viscosity. RESULTS After adjusting the initial stenosis degree and MRA stage of MMD, an SP of ≥ 20% and an SPR of ≥ 10%/year were associated with the highest-quartile WSSVs for all individual vessels and for MCAs and ICAs separately. For each hemisphere, an MSP of ≥ 20% and an MSPR of ≥ 10%/year were associated with the highest-quartile mean WSSVs. Furthermore, significant SP was highly correlated with vascular complications, and the highest-quartile mean WSSV was independently associated with vascular complications in relevant hemispheres. CONCLUSIONS An elevated WSSV is an independent predictor for SP and vascular complications in nonoccluded MMD.

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