CD36 is a membrane glycoprotein that is present on various types of cells, including monocytes, macrophages, microvascular endothelial cells, adipocytes and platelets. Macrophage CD36 participates in atherosclerotic arterial lesion formation through its interaction with oxidized low-density lipoprotein (oxLDL), which triggers signaling cascades for inflammatory responses. CD36 functions in oxLDL uptake and foam cell formation, which is the initial critical stage of atherosclerosis. In addition, oxLDL via CD36 inhibits macrophage migration, which may be a macrophage-trapping mechanism in atherosclerotic lesions. The role of CD36 was examined in in vitro studies and in vivo experiments, which investigated various functions of CD36 in atherosclerosis and revealed that CD36 deficiency reduces atherosclerotic lesion formation. Platelet CD36 also promotes atherosclerotic inflammatory processes and is involved in thrombus formation after atherosclerotic plaque rupture. Because CD36 is an essential component of atherosclerosis, defining the function of CD36 and its corresponding signaling pathway may lead to a new treatment strategy for atherosclerosis.
Animals ; Antigens, CD36/chemistry/genetics/*metabolism ; Atherosclerosis/*metabolism/pathology ; Humans ; Macrophages/metabolism/pathology ; Plaque, Atherosclerotic/*metabolism/pathology

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

OBJECTIVETo observe the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the unstable plaque of patients with acute coronary syndrome (ACS), and the impact of leukotriene B4 (LTB4) on the EMMPRIN expression in macrophages.

METHODSThe EMMPRIN expression was detected by immunohistochemistry in 11 unstable plaques from patients with ACS. Protein expression of EMMPRIN was evaluated by Western blot on macrophages differentiated from THP-1 which were stimulated with LTB4 in the absence or presence of LTB4 antagonist U75302. There are 8 study groups: 1-THP-1, 2-8-the macrophages derived from THP-1, 2-6-macrophages were stimulated by LTB4 (0, 10(-10), 10(-9), 10(-8) and 10(-7) mol/L) for 24 h, 7-8-the macrophages were pretreated by 10(-6) mol/L or 10(-7) mol/L U75302 2 h before the LTB4 (10(-7) mol/L) stimulation.

RESULTSAbundant EMMPRIN expression was detected in macrophages and smooth muscle cells of unstable plaques from ACS patients. As to the THP-1 derived macrophages, EMMPRIN expression was significantly upregulated in a concentration-dependent manner in LTB4 stimulated groups, which was significantly higher in group 3-6 than in the THP-1 group (group 1) and macrophages group (group 2) (all P < 0.05) and pretreatment with U75302 significantly reduced the LTB4 induced upregulation of EMMPRIN in a dose-dependent manner (P < 0.05).

CONCLUSIONEMMPRIN expression is enhanced in macrophages and smooth muscle cells on unstable coronary artery plaques from ACS patients. LTB4 could stimulate EMMPRIN expression on THP-1 derived macrophages suggesting that LTB4 and EMMPRIN might be both involved in the formation and progression of unstable plaques, future studies are warranted to explore if LTB4 and EMMPRIN antagonists are effective or not for treating patients with ACS.

Acute Coronary Syndrome ; metabolism ; pathology ; Basigin ; metabolism ; Cell Line ; Humans ; Leukotriene B4 ; metabolism ; pharmacology ; Macrophages ; drug effects ; metabolism ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; Plaque, Atherosclerotic ; metabolism

Atherosclerosis is an inflammatory disease as well as a lipid disorder. Atherosclerotic plaque formed in vessel walls may cause ischemia, and the rupture of vulnerable plaque may result in fatal events, like myocardial infarction or stroke. Because morphological imaging has limitations in diagnosing vulnerable plaque, molecular imaging has been developed, in particular, the use of nuclear imaging probes. Molecular imaging targets various aspects of vulnerable plaque, such as inflammatory cell accumulation, endothelial activation, proteolysis, neoangiogenesis, hypoxia, apoptosis, and calcification. Many preclinical and clinical studies have been conducted with various imaging probes and some of them have exhibited promising results. Despite some limitations in imaging technology, molecular imaging is expected to be used both in the research and clinical fields as imaging instruments become more advanced.
Atherosclerosis/*diagnosis/pathology/radiography ; Endothelial Cells/metabolism ; Humans ; Inflammation/pathology ; Lipoproteins, LDL/metabolism ; Macrophages/immunology/metabolism ; Plaque, Atherosclerotic ; Positron-Emission Tomography ; Tomography, Emission-Computed, Single-Photon

BACKGROUNDAutophagy has been found to be involved in animal and cell models of atherosclerosis, but to date, it lacks general observation in human atherosclerotic plaques. Here, we investigated autophagy in smooth muscle cells (SMCs), endothelial cells (ECs), and macrophages in human atherosclerotic plaques via transmission electron microscopy (TEM), western blotting, and immunohistochemistry analysis.

METHODSThe histopathologic morphology of these plaques was observed via hematoxylin and eosin staining. The ultrastructural morphology of the SMCs, ECs, and macrophages in these plaques was observed via TEM. The localization of microtubule-associated protein 1 light chain 3 (MAP1-LC3), a relatively special maker of autophagy, in plaques was observed by double fluorescent immunochemistry and western blotting.

RESULTSAll of these human atherosclerotic plaques were considered advanced and unstable in histologically observation. By double fluorescent immunochemistry, the expression of LC3-II increased in the SMCs of the fibrous cap, the macrophages, and the microvascular ECs of the plaque shoulders. The protein level of LC3-II by western blotting significantly increased in plaques compared with normal controls. In addition, TEM observation of plaques revealed certain features of autophagy in SMCs, ECs, and macrophages including the formation of myelin figures, vacuolization, and the accumulation of inclusions in the cytosol. These results indicate that autophagy is activated in SMCs, ECs, and macrophages in human advanced atherosclerotic plaques.

CONCLUSIONSOur study is to demonstrate the existence of autophagy in human atherosclerotic plaques by different methods, which may contribute to the development of pharmacological approaches to stabilize vulnerable and rupture-prone lesions.

Atherosclerosis ; metabolism ; physiopathology ; Autophagy ; physiology ; Endothelial Cells ; pathology ; Humans ; In Vitro Techniques ; Microscopy, Electron, Transmission ; Microtubule-Associated Proteins ; metabolism ; Myocytes, Smooth Muscle ; pathology ; Plaque, Atherosclerotic ; metabolism ; physiopathology ; ultrastructure

OBJECTIVETo explore the association of fractalkine (FKN) and CD11c expressions oncommon carotid artery atherosclerotic plaques from apoE(-/-) mice with the severity of atherosclerotic lesions.

METHODSTotally 24 apoE(-/-) mice were divided into two groups and fed on a high-fat diet or a normal diet for 12 weeks. Then the blood lipids as well as the plaque area and vascular stenosis rate of the common carotid artery were measured to evaluate the severity of atherosclerotic lesions of the animals. Moreover, immunohistochemical staining was performed to examine the levels of FKN and CD11c expression.

RESULTSThe plaque areas and vascular stenosis rates of the common carotid artery in the experimental group were remarkably larger than those in control group (about 4-fold and 2-fold, respectively). The level of FKN expression in the experimental group was 2 times of that in the control group (P<0.05), and the number of CD11c (+) cells in the plaques in the experimental group was about 4 times of than in the control group (P<0.05).

CONCLUSIONThe expressions of chemokine and FKN remarkably increase in apoE (-/-) atherosclerotic plaques, suggesting that chemokine and FKN may paly important roles in the development of atherosclerosis.

Animals ; Atherosclerosis ; metabolism ; pathology ; CD11 Antigens ; metabolism ; Chemokine CX3CL1 ; metabolism ; Diet, High-Fat ; Disease Models, Animal ; Mice ; Mice, Knockout ; Plaque, Atherosclerotic ; pathology

OBJECTIVETo observe the atherogenic lesion progress in a novel ischemia/reperfusion induced atherosclerosis model in the carotid artery of rats.

METHODSRats were divided into normal control, sham-operated control and ischemia-reperfusion injury (IRI) groups (n = 10 each). IRI was induced by 30 min carotid artery occlusion with a 2 cm long artery clips in anesthetized rats. Four weeks later, hematoxylin and eosin (HE) and immunohistochemical stain were performed on carotid arteries of various groups. The ratio of neointima area/media area (I/M) and expression of platelet endothelial cell adhesion molecule (PECAM-1/CD31) were compared among groups.

RESULTS(1) Neointimal hyperplasia was detected in carotid artery of IRI group and the I/M ratio was significantly higher than in normal control and sham-operated groups (1.328 ± 0.301 vs. 0.011 ± 0.004 and 0.017 ± 0.008, all P < 0.01). (2) Small to large-sized neointima were found in the IRI group and the small sized intima was stable while large sized intima which covered the whole cavity was instable and underwent spontaneous rupture and thrombosis formation. (3) CD31 expression was significantly upregulated in carotid artery of IRI group corresponding to the instability of neointima in this group.

CONCLUSIONIschemia-reperfusion injury of carotid artery could result in atheroma in rats, this model could be used for future research on the pathogenesis of atherosclerosis. Our results show that endothelium injury of the arteries is the key factor to trigger atheroma and responsible for the disruption of the plaque.

Animals ; Carotid Artery, Common ; pathology ; Disease Models, Animal ; Endothelium, Vascular ; pathology ; Male ; Plaque, Atherosclerotic ; pathology ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury

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*

OBJECTIVETo elucidate the roles of monocyte chemotactic factors (MCP-1, RANTES and Fractalkine) on the vulnerability of atherosclerotic plaques in patients with stable (SAP) and unstable angina pectoris (UAP).

METHODSPatients with SAP (n = 50) and UAP (n = 50) underwent coronary angiography (CAG) and intravenous ultrasound (IVUS) were included in the study. Monocyte chemotaxis was assayed by the transwell chamber. Concentrations of hs-CRP, MCP-1, RANTES and Fractalkine were measured by Enzyme-linked-immunosorbent assay (ELISA). mRNA expression of MCP-1, RANTES and Fractalkine in the monocytes was detected by RT-PCR.

RESULTSIVUS evidenced soft lipid plaques in 48% UAP patients and in 16% SAP patients (P < 0.05). SAP patients had mainly fibrous and mixed plaques. Plaque burden and vascular remodeling index were significantly higher in UAP patients than in SAP patients (P < 0.01). The averaged number of migrated monocytes in the UAP patients were higher than that in patients with SAP (P < 0.01). Concentration of hs-CRP, MCP-1, RANTES and Fractalkine were significantly higher in UAP patients than those of SAP patients (P < 0.05 or P < 0.01). mRNA expression of MCP-1, RANTES and Fractalkine in patients with UAP was significantly higher than those of SAP patients (P < 0.05).

CONCLUSIONUpregulated monocyte chemotactic factors (MCP-1, RANTES and Fractalkine) might promote coronary plaque vulnerability in UAP patients.

Angina Pectoris ; metabolism ; pathology ; Angina, Unstable ; metabolism ; pathology ; Chemokine CCL2 ; metabolism ; Chemokine CCL5 ; metabolism ; Chemokine CX3CL1 ; metabolism ; Coronary Angiography ; Female ; Humans ; Male ; Middle Aged ; Plaque, Atherosclerotic ; pathology ; RNA, Messenger ; genetics

OBJECTIVETo study the expression of COX-2 and pregnancy associate plasma protein A (PAPP-A) in coronary arteries and their relationship with acute coronary syndrome.

METHODSTwenty-one autopsy cases with acute coronary syndrome encountered during the period from 2002 to 2007 were enrolled into the study. Another 21 autopsy cases without evidence of acute coronary syndrome were used as the controls. The right and left coronary arteries of each group were dissected, embedded and processed as paraffin sections. Immunohistochemical study for CD68 and alpha-actin was performed to highlight the presence of macrophages and smooth muscle cells, respectively. The expression of COX-2 and PAPP-A was evaluated.

RESULTSIn the acute coronary syndrome group, COX-2 was localized mainly in the cytoplasm of endothelial cells, macrophages and smooth muscle cells. COX-2 expression in the cytoplasm of smooth muscle cells (28.60%) was significantly higher than that in the control group (4.76%, chi(2) = 14.13, P< 0.05). There was a positive correlation on COX-2 and PAPP-A expression in smooth muscle cells of the media layer of coronary arteries in acute coronary syndrome group (r = 0.88, P < 0.05). The expression of PAPP-A in smooth muscle cells of the media layer in coronary arteries not associated with plaque formation, was higher than that when there were atherosclerotic plaques (chi(2) = 10.36, P < 0.05).

CONCLUSIONIn coronary arteries, COX-2 and PAPP-A play certain roles in the pathogenesis of acute coronary syndrome.

Acute Coronary Syndrome ; metabolism ; pathology ; Adult ; Aged ; Autopsy ; Coronary Vessels ; metabolism ; pathology ; Cyclooxygenase 2 ; metabolism ; Female ; Humans ; Middle Aged ; Myocytes, Smooth Muscle ; metabolism ; Plaque, Atherosclerotic ; metabolism ; Pregnancy ; Pregnancy-Associated Plasma Protein-A ; metabolism ; Young Adult