The present study aimed to investigate the protective effect of S-propargyl-cysteine (SPRC) on atherosclerosis progression in mice. A mouse model of vulnerable atherosclerotic plaque was created in ApoE^-/- mice by carotid artery tandem stenosis (TS) combined with a Western diet. Macrophotography, lipid profiles, and inflammatory markers were measured to evaluate the antiatherosclerotic effects of SPRC compared to atorvastatin as a control. Histopathological analysis was performed to assess the plaque stability. To explore the protective mechanism of SPRC, human umbilical vein endothelial cells (HUVECs) were cultured in vitro and challenged with oxidized low-density lipoprotein (ox-LDL). Cell viability was determined with a Cell Counting Kit-8 (CCK-8). Endothelial nitric oxide synthase (eNOS) phosphorylation and mRNA expression were detected by Western blot and RT-qPCR respectively. The results showed that the lesion area quantified by en face photographs of the aortic arch and carotid artery was significantly less, plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were reduced, plaque collagen content was increased and matrix metalloproteinase-9 (MMP-9) was decreased in 80 mg/kg per day SPRC-treated mice compared with model mice. These findings support the role of SPRC in plaque stabilization. In vitro studies revealed that 100 μmol/L SPRC increased the cell viability and the phosphorylation level of eNOS after ox-LDL challenge. These results suggest that SPRC delays the progression of atherosclerosis and enhances plaque stability. The protective effect may be at least partially related to the increased phosphorylation of eNOS in endothelial cells.
Animals ; Humans ; Mice ; Atherosclerosis ; Cholesterol/metabolism* ; Cysteine/pharmacology* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Lipoproteins, LDL/pharmacology* ; Nitric Oxide Synthase Type III/metabolism* ; Phosphorylation ; Plaque, Atherosclerotic/pathology*

OBJECTIVE: To analyse the correlation between the characteristics of coronary plaque in coronary heart disease (CHD) patients with phlegm-blood stasis syndrome (PBS) and blood stasis syndrome (BSS). METHODS: Patients were divided into different groups based on Chinese medicine (CM) syndrome differentiation. The baseline demographics and clinical variables were collected from the medical records. Additionally, the characteristics of plaque and pathological manifestations in coronary artery were evaluated using intravascular ultrasound (IVUS). RESULTS: A total of 213 CHD patients were enrolled in two groups: 184 were diagnosed with PBS and the remaining 29 were diagnosed with BSS. There were no significant differences in age, body mass index, proportions of patients with high blood pressure, diabetes mellitus, smoking, hyperlipidemia, history of coronary artery bypass graft and percutaneous coronary intervention, medications, index from cardiac ultrasound image, blood lipids and C-reactive protein between the two groups (P>0.05), except gender, weight and proportions of IVUS observed target vessels (P<0.05 or P<0.01). More adverse events such as acute myocardial infarction (P=0.003) and unstable angina (P=0.048) were observed in BSS. Additionally, dissection, thrombus and coronary artery ectasia were significantly increased in BSS (P<0.05 or P<0.01). In contrast, PBS had more patients with stable angina and chronic total occlusion with significantly higher SYNTAX (synergy between percutaneous coronary intervention with Taxus and coronary artery bypass surgery) scores (P<0.05 or P<0.01). Moreover, dense-calcium was significantly elevated in PBS (P<0.01). CONCLUSIONS Coronary plaque characteristics were correlated with different CM syndromes. Patients with PBS were associated with a higher degree of calcified plaque and severe coronary artery stenosis, indicating poor clinical prognosis but with a low probability of acute coronary events. In contrast, the degree of calcified plaque in patients with BSS remained relatively low, and plaque was more vulnerable, resulting in the possibility of the occurrence of acute coronary events remaining high.
Coronary Angiography ; Coronary Artery Disease/diagnostic imaging* ; Coronary Vessels/pathology* ; Cross-Sectional Studies ; Humans ; Medicine, Chinese Traditional ; Percutaneous Coronary Intervention ; Plaque, Atherosclerotic/diagnostic imaging* ; Syndrome ; Ultrasonography, Interventional/methods*

Objective: To observe the effect of lipid regulating therapy on carotid atherosclerotic plaque in diabetic patients. Methods: The REACH study, conducted between March 2009 and February 2012, enrolled asymptomatic patients with magnetic resonance imaging (MRI) confirmed carotid atherosclerotic plaque, who had never taken lipid-lowering drugs. Patients were treated with a moderate dose of rosuvastatin for 24 months. Blood lipid levels were measured and carotid MRI was performed at baseline, 3 and 24 months after treatment. The volume of carotid wall and lipid-rich necrotic core (LRNC) were measured by image analysis software. This study retrospectively analyzed patients in the REACH study. Patients were divided into diabetes group and non-diabetic group. The changes of blood lipid level and MRI parameters of carotid atherosclerotic plaque were compared between the two groups and their correlation was analyzed. Results: A total of 38 patients with carotid atherosclerotic plaque were included in this study, including 13 patients (34.2%) in the diabetic group and 25 patients (65.8%) in the non-diabetic group. Baseline parameters were comparable between the two groups, except higher HbA1c level in diabetes group (P<0.05). Compared with baseline, the total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels were significantly decreased at 3 and 24 months in both two groups (P<0.05). The change of high-density lipoprotein cholesterol (HDL-C) in diabetes group was not obvious, while it was significantly increased in non-diabetic group at 24 months ((1.38±0.33) mmol/l vs. (1.26±0.26) mmol/l, P<0.05). MRI results showed that the volume and percentage of LRNC remained unchanged at 3 months, slightly decreased at 24 months (64.86 (45.37, 134.56) mm³ vs. 75.76 (48.20, 115.64) mm³, P>0.05) and (15.84% (11.47%, 24.85%) vs. 16.95% (11.64%, 22.91%), P>0.05) in diabetic group. In non-diabetic group, the volume and percentage of LRNC were significantly decreased at 3 months (63.01 (44.25, 188.64) mm³ vs. 72.49 (51.91, 199.59) mm³, P<0.05) and (13.76% (8.81%, 27.64%) vs. 16.04% (11.18%, 27.05%), P<0.05) respectively. Both parameters further decreased to (55.63 (27.18, 179.40) mm³) and (12.71% (8.39%, 24.41%)) at 24 months (both P<0.05). Wall volume, lumen volume and percent wall volume (PWV) were not affected post therapy in both two groups(P>0.05). There were no correlations between the changes of plaque parameters including volume and percentage of LRNC, wall volume, lumen volume, PWV and the changes of blood lipid parameters (TC, LDL-C, HDL-C and TG) in 3 and 24 months (P>0.05). Conclusion: Lipid-lowering therapy possesses different effects on carotid atherosclerotic plaque in diabetic and non-diabetic patients, and the LRNC improvement is more significant in non-diabetic patients as compared to diabetic patients.
Carotid Arteries/pathology* ; Carotid Artery Diseases/drug therapy* ; Cholesterol, HDL/therapeutic use* ; Cholesterol, LDL ; Diabetes Mellitus ; Humans ; Magnetic Resonance Imaging/methods* ; Necrosis/pathology* ; Plaque, Atherosclerotic/drug therapy* ; Retrospective Studies ; Rosuvastatin Calcium/therapeutic use*

OBJECTIVE: To investigate the prognosis of patients with vulnerable plaque indicated by coronary CT angiography (CCTA). METHODS: Totally 1963 patients underwent CCTA from February 2nd 2015 to September 13th 2015, and 2728 coronary borderline lesions (stenosis of 50%-70%) were detected. Among them 804 patients had vulnerable plaques and 1159 patients had stable plaques. The primary endpoint was major cardiac adverse events (MACE), including cardiac death, acute myocardial infarction and target lesion revascularization. RESULTS: Patients were followed up for a mean follow-up of 27.4±2.3 months. The incidence of MACE in the vulnerable plaque group was significantly higher than that in the stable plaque group (10.8%vs 2.3%, < 0.01). After adjusting for age, gender, smoking, hypertension, diabetes, hyperlipidemia, the MACE hazard ratio () in the vulnerable plaque group was 5.022 (95% :3.254-7.751, < 0.01).Subgroup analysis showed that in the vulnerable plaque group, the incidence of MACE in patients taking antiplatelet and statin ≤3 months and those taking antiplatelet and statin > 3 months was 17.0%and 5.8%, respectively (=3.149, 95% :1.987-4.992, < 0.01); but the difference did not seen in stable plaque group (=1.721, 95% :0.798-3.712, >0.05). CONCLUSIONS This study confirmed the risk of MACE in patients with vulnerable plaque detected by CCTA and the drug treatment may reduce the risk for patients with vulnerable plaque.
Computed Tomography Angiography ; Coronary Angiography ; Coronary Artery Disease ; diagnostic imaging ; Coronary Stenosis ; diagnostic imaging ; Humans ; Infant ; Plaque, Atherosclerotic ; diagnostic imaging ; pathology ; Prognosis ; Risk Factors

In the background of the high incidence and high mortality of cardiovascular diseases,atherosclerosis is the main pathological feature of cardiovascular diseases and the core pathological basis for disease progression. In the evolution of atherosclerotic plaques,the rupture of unstable plaques,plaque shedding and formation of thrombosis are the most dangerous parts. In this process,the formation of plaque fibrosis is the core mechanism regulating plaque stability. Additionally,fibrosis reflects dynamic changes in the inflammatory processes and pathological changes. In view of the inflammation regulation and fibrosis regulation,this paper clarified the process of atherosclerotic plaque,explained the roles of relevant inflammatory cells and cytokines in plaque stability,and summed up drug researches related with stable plaque in recent years. In the future,improving the fibrosis will be a new idea for stabilizing plaque in atherosclerosis drug development.
Atherosclerosis ; drug therapy ; pathology ; Cytokines ; Fibrosis ; Humans ; Inflammation ; Plaque, Atherosclerotic ; drug therapy ; pathology ; Thrombosis ; drug therapy ; pathology

OBJECTIVE: Saphenous vein grafts disease (SVGD) is a common complication after coronary artery bypass graft (CABG) and normally treated by percutaneous coronary intervention (PCI). The most common complication after SVG-PCI is slow or no-reflow. It is known that the no-reflow phenomenon occurs in up to 15% of the SVG-PCI and is associated with high risk of major adverse cardiac events (MACEs) and mortality, therefore, it is important to investigate the factors that could predict the clinical outcome of PCI for risk stratification and guiding interventions. In recent years, the spectral analysis of intravascular ultrasound (IVUS) radiofrequency data (virtual histology-IVUS [VH-IVUS]) has been used to provide quantitative assessment on both plaque compositions and morphologic characteristics. DATA SOURCES: The PubMed, Embase, and Central databases were searched for possible relevant studies published from 1997 to 2018 using the following index keywords: "Coronary artery bypass grafting," "Saphenous venous graft disease," "Virtual histology-intravascular ultrasound," "Virtual histology-intravascular ultrasound," and "Percutaneous coronary intervention." STUDY SELECTION: The primary references were Chinese and English articles including original studies and literature reviews, were identified and reviewed to summarize the advances in the application of VH-IVUS techniques in situ vascular and venous graft vascular lesions. RESULTS: With different plaque components exhibiting a defined spectrum, VH-IVUS can classify atherosclerotic plaque into four types: fibrous tissue (FT), fibro fatty (FF), necrotic core (NC), and dense calcium (DC). The radiofrequency signal is mathematically transformed into a color-coded representation, including lipid, fibrous tissue, calcification, and necrotic core. Several studies have demonstrated the independent relationship between VH-IVUS-defined plaque classification or plaque composition and MACEs, but a significant association between plaque components and no-reflow after PCI in acute coronary syndrome. In recent years, VH-IVUS are applied to assess the plaque composition of SVGD, based on the similarity of pathophysiological mechanisms between coronary artery disease (CAD) and SVGD, further studies with the larger sample size, the long-term follow-up, multicenter clinical trials may be warranted to investigate the relationship between plaque composition of saphenous vein graft (SVG) by VH-IVUS and clinical outcomes in patients with SVGD undergoing PCI. CONCLUSIONS In degenerative SVG lesions, VH-IVUS found that plaque composition was associated with clinical features, future studies need to explore the relationship between VH-IVUS defined atherosclerotic plaque components and clinical outcomes in SVGD patients undergoing PCI, an innovative prediction tool of clinical outcomes can be created.
Coronary Artery Bypass ; adverse effects ; Coronary Artery Disease ; pathology ; Female ; Humans ; Male ; Percutaneous Coronary Intervention ; adverse effects ; Plaque, Atherosclerotic ; pathology ; Saphenous Vein ; pathology ; Ultrasonography, Interventional

BACKGROUND: Asymptomatic coronary artery stenosis (ACAS) ≥50% is common in patients with acute ischemic cerebrovascular disease (AICVD), which portends a poor cardiovascular and cerebrovascular prognosis. Identifying ACAS ≥50% early may optimize the clinical management and improve the outcomes of these high-risk AICVD patients. This study aimed to investigate whether aortic arch plaque (AAP), an early atherosclerotic manifestation of brain blood-supplying arteries, could be a predictor for ACAS ≥50% in AICVD. METHODS: In this cross-sectional study, atherosclerosis of the coronary and brain blood-supplying arteries was simultaneously evaluated using one-step computed tomography angiography (CTA) in AICVD patients without coronary artery disease history. The patients were divided into ACAS ≥50% and non-ACAS ≥50% groups according to whether CTA showed stenosis ≥50% in at least one coronary arterial segment. The AAP characteristics of CTA were depicted from aspects of thickness, extent, and complexity. RESULTS: Among 118 analyzed patients with AICVD, 29/118 (24.6%) patients had ACAS ≥50%, while AAPs were observed in 86/118 (72.9%) patients. Increased AAP thickness per millimeter (adjusted odds ratio [OR]: 1.56, 95% confidence interval [CI]: 1.18-2.05), severe-extent AAP (adjusted OR: 13.66, 95% CI: 2.33-80.15), and presence of complex AAP (adjusted OR: 7.27, 95% CI: 2.30-23.03) were associated with ACAS ≥50% among patients with AICVD, independently of clinical demographics and cervicocephalic atherosclerotic stenosis. The combination of AAP thickness, extent, and complexity predicted ACAS ≥50% with an area under the receiver-operating characteristic curve of 0.78 (95% CI: 0.70-0.85, P < 0.001). All three AAP characteristics provided additional predictive power beyond cervical and intracranial atherosclerotic stenosis for ACAS ≥50% in AICVD (all P < 0.05). CONCLUSIONS Thicker, severe-extent, and complex AAP were significant markers of the concomitant ACAS ≥50% in AICVD, possibly superior to the indicative value of cervical and intracranial atherosclerotic stenosis. As an integral part of atherosclerosis of brain blood-supplying arteries, AAP should not be overlooked in predicting ACAS ≥50% for patients with AICVD.
Aged ; Aorta, Thoracic ; pathology ; Cerebrovascular Disorders ; diagnosis ; Coronary Stenosis ; diagnosis ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Odds Ratio ; Plaque, Atherosclerotic ; diagnosis ; Risk Factors

The term “vulnerable plaque” denotes the plaque characteristics that are susceptible to coronary thrombosis. Previous post-mortem studies proposed 3 major mechanisms of coronary thrombosis: plaque rupture, plaque erosion, and calcified nodules. Of those, characteristics of rupture-prone plaque have been extensively studied. Pathology studies have identified the features of rupture-prone plaque including thin fibrous cap, large necrotic core, expansive vessel remodeling, inflammation, and neovascularization. Intravascular imaging modalities have emerged as adjunctive tools of angiography to identify vulnerable plaques. Multiple devices have been introduced to catheterization laboratories to date, including intravascular ultrasound (IVUS), virtual-histology IVUS, optical coherence tomography (OCT), coronary angioscopy, and near-infrared spectroscopy. With the use of these modalities, our understanding of vulnerable plaque has rapidly grown over the past several decades. One of the goals of intravascular imaging is to better predict and prevent future coronary events, for which prospective observational data is still lacking. OCT delineates microstructures of plaques, whereas IVUS visualizes macroscopic vascular structures. Specifically, plaque erosion, which has been underestimated in clinical practice, is gaining an interest due to the potential of OCT to make an in vivo diagnosis. Another potential future avenue for intravascular imaging is its use to guide treatment. Feasibility of tailored therapy for acute coronary syndromes (ACS) guided by OCT is under investigation. If it is proven to be effective, it may potentially lead to major shift in the management of millions of patients with ACS every year.
Acute Coronary Syndrome ; Angiography ; Angioscopy ; Catheterization ; Catheters ; Coronary Thrombosis ; Diagnosis ; Humans ; Inflammation ; Pathology ; Plaque, Atherosclerotic ; Prospective Studies ; Rupture ; Spectroscopy, Near-Infrared ; Tomography, Optical Coherence ; Ultrasonography ; Ultrasonography, Interventional

OBJECTIVEAtherosclerosis is an inflammatory process that results in complex lesions or plaques that protrude into the arterial lumen. Carotid atherosclerotic plaque rupture, with distal atheromatous debris embolization, causes cerebrovascular events. This review aimed to explore research progress on the risk factors and outcomes of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention.

DATA SOURCESWe searched the PubMed database for recently published research articles up to June 2016, with the key words of "risk factors", "outcomes", "blood components", "molecular mechanisms", "cellular mechanisms", and "human carotid atherosclerotic plaques".

STUDY SELECTIONThe articles, regarding the latest developments related to the risk factors and outcomes, atherosclerotic plaque composition, blood components, and consequences of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention, were selected.

RESULTSThis review described the latest researches regarding the interactive effects of both traditional and novel risk factors for human carotid atherosclerotic plaques, novel insights into human carotid atherosclerotic plaque composition and blood components, and consequences of human carotid atherosclerotic plaque.

CONCLUSIONCarotid plaque biology and serologic biomarkers of vulnerability can be used to predict the risk of cerebrovascular events. Furthermore, plaque composition, rather than lesion burden, seems to most predict rupture and subsequent thrombosis.

Biomarkers ; blood ; Carotid Stenosis ; blood ; epidemiology ; metabolism ; pathology ; Humans ; Plaque, Atherosclerotic ; blood ; complications ; metabolism ; pathology ; Risk Factors

PURPOSE: Appropriate animal models of atherosclerotic plaque are crucial to investigating the pathophysiology of atherosclerosis, as well as for the evaluation of the efficacy and safety of vascular devices. We aimed to develop a novel animal model that would be suitable for the study of advanced atherosclerotic lesions in vivo. MATERIALS AND METHODS: Atherosclerotic plaque was induced in 24 iliac arteries from 12 rabbits by combining a high cholesterol diet, endothelial denudation, and injection into the vessel wall with either saline (n=5), olive oil (n=6), or inflammatory proteins [n=13, high-mobility group protein B1 (HMGB1) n=8 and tumor necrosis factor (TNF)-α n=5] using a Cricket™ Micro-infusion catheter. Optical coherence tomography (OCT) was performed to detect plaque characteristics after 4 weeks, and all tissues were harvested for histological evaluation. RESULTS: Advanced plaque was more frequently observed in the group injected with inflammatory proteins. Macrophage infiltration was present to a higher degree in the HMGB1 and TNF-α groups, compared to the oil or saline group (82.1±5.1% and 94.6±2.2% compared to 49.6±14.0% and 46.5±9.6%, p-value<0.001), using RAM11 antibody staining. On OCT, lipid rich plaques were more frequently detected in the inflammatory protein group [saline group: 2/5 (40%), oil group: 3/5 (50%), HMGB1 group: 6/8 (75%), and TNF-α group: 5/5 (100%)]. CONCLUSION: These data indicate that this rabbit model of atherosclerotic lesion formation via direct injection of pro-inflammatory proteins into the vessel wall is useful for in vivo studies investigating atherosclerosis.
Animals ; Cholesterol, Dietary/administration & dosage ; *Disease Models, Animal ; Endothelium/surgery ; HMGB1 Protein/*adverse effects ; Iliac Artery/diagnostic imaging/pathology/surgery ; Injections, Intra-Arterial ; Macrophages ; Male ; Olive Oil/adverse effects ; Plaque, Atherosclerotic/*chemically induced/diagnostic imaging/pathology ; Rabbits ; Sodium Chloride/adverse effects ; Tomography, Optical Coherence ; Tumor Necrosis Factor-alpha/*adverse effects