Calcium deposition within coronary atherosclerotic lesion: Implications for plaque stability

2020 ◽  
Vol 306 ◽  
pp. 85-95 ◽  
Author(s):  
Hiroyuki Jinnouchi ◽  
Yu Sato ◽  
Atsushi Sakamoto ◽  
Anne Cornelissen ◽  
Masayuki Mori ◽  
...  
Keyword(s):  
Atherosclerotic Lesion ◽  
Calcium Deposition ◽  
Plaque Stability ◽  
Coronary Atherosclerotic Lesion

Silencing of junctional adhesion molecule-like protein attenuates atherogenesis and enhances plaque stability in ApoE−/− mice

2019 ◽  
Vol 133 (11) ◽  
pp. 1215-1228 ◽  
Author(s):  
Yu Sun ◽  
Juan Guan ◽  
Yunfeng Hou ◽  
Fei Xue ◽  
Wei Huang ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Wound Repair ◽  
Inflammatory Responses ◽  
Atherosclerotic Lesion ◽  
Atherosclerotic Plaques ◽  
Plaque Stability ◽  
Fibrous Cap ◽  
Enhanced Expression

Abstract Background: Although junctional adhesion molecule-like protein (JAML) has recently been implicated in leukocyte recruitment during inflammation and wound repair, its role in atherosclerosis remains to be elucidated. Methods and results: First, we showed that JAML was strongly expressed in atherosclerotic plaques of cardiovascular patients. Similar results were obtained with atherosclerotic plaques of ApoE−/− mice. Co-immunofluorescence staining showed that JAML was mainly expressed in macrophages. Enhanced expression of JAML in cultured macrophages was observed following exposure of the cells to oxLDL. The functional role of JAML in atherosclerosis and macrophages function was assessed by interference of JAML with shRNA in vivo and siRNA in vitro. Silencing of JAML in mice significantly attenuated atherosclerotic lesion formation, reduced necrotic core area, increased plaque fibrous cap thickness, decreased macrophages content and inflammation. In addition, histological staining showed that JAML deficiency promoted plaques to stable phenotype. In vitro, JAML siRNA treatment lowered the expression of inflammatory cytokines in macrophages treated with oxLDL. The mechanism by which JAML mediated the inflammatory responses may be related to the ERK/NF-κB activation. Conclusions: Our results demonstrated that therapeutic drugs which antagonize the function of JAML may be a potentially effective approach to attenuate atherogenesis and enhance plaque stability.

Long term dietary vitamin E reduces atherosclerotic lesion size and increases plaque stability in heterozygous LDL-receptor deficient mice

2001 ◽  
Vol 2 (2) ◽  
pp. 109
Author(s):  
O.L. Volger ◽  
J. van der Boom ◽  
W. van Duyvenvoorde ◽  
E.H. Offerman ◽  
R. Leenen ◽  
...  
Keyword(s):  
Vitamin E ◽  
Ldl Receptor ◽  
Atherosclerotic Lesion ◽  
Lesion Size ◽  
Dietary Vitamin ◽  
Plaque Stability ◽  
Deficient Mice

scholarly journals The correlation between lipoprotein(a) and coronary atherosclerotic lesion is stronger than LDL-C, when LDL-C is less than 104 mg/dL

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chuang Li ◽  
Qiwen Chen ◽  
Mei Zhang ◽  
Yin Liu ◽  
Yushun Chu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Clinical Characteristics ◽  
Atherosclerotic Lesion ◽  
Atherosclerotic Cardiovascular Disease ◽  
Spearman Correlation ◽  
Gensini Score ◽  
Logistic Regressions ◽  
Coronary Atherosclerotic Lesion

Abstract Background Lp(a) and LDL-C are both risk factors of atherosclerotic cardiovascular disease (ASCVD). But there was a contradiction point in LDL-C and Lp(a) control. The appropriate level of LDL-C and Lp(a) in the prevention of ASCVD is still pending. Objective To investigate the correlation of Lp(a) and coronary atherosclerotic lesion, and find out the balance point in LDL-C and Lp(a) control. Method 3449 patients were divided to coronary atherosclerotic heart disease (CAHD) Group and Non-CAHD Group based on the result of coronary angiography. The clinical characteristics were compared, and Logistic regressions were applied to find the CAHD risk factors in total, High-LDL-C Group (LDL-C ≥ 100 mg/dL) and Low-LDL-C Group (LDL-C < 100 mg/dL) patients. Spearman correlation analysis of Lp(a), LDL-C and Gensini Score was performed in patients with different LDL-C concentration. Results Except male and diabetes, the traditional CAHD risk factors were well matched between two groups. But triglyceride, LDL-C and Lp(a) were higher, HDL-C and Apo-A1 were lower in CAHD group (2771). In the Logistic regression analysis, diabetes, LDL-C and Lp(a) are risk factors of CAHD in all patients, while in High-LDL-C Group, they were age, LDL-C, non-HDL-C and ApoB, in Low-LDL-C Group, they were age, Lp(a) and ApoB. Lp(a) correlated with Gensini with coefficient r = 0.41 in all patients, 0.67 in Low-LDL-C Group and 0.32 in High-LDL-C Group. The coefficient r for Lp(a) and Gensini decreased, while the r for LDL-C and Gensini increased with LDL-C concentration increasing. The two fitted lines of rs crossed at LDL-C = 2.7 mmol/L (104 mg/dL). Conclusion Lp(a) was the risk factor of CAHD in patients with LDL-C < 100 mg/dL. The correlation between Lp(a) and Gensini was influenced by LDL-C concentration, and the correlation was stronger than LDL-C when LDL-C < 104 mg/dl.

scholarly journals β-carotene Enhances Atherosclerosis Resolution in A Reversible Murine Model of Atherosclerosis

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 68-68
Author(s):  
Asma'a Albakri ◽  
Johana Coronel ◽  
Sanjana Tamane ◽  
Molly Black ◽  
Edward Fisher ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Atherosclerotic Lesion ◽  
Density Lipoprotein ◽  
Plaque Stability ◽  
Hepatic Expression ◽  
Funding Sources ◽  
Atherosclerotic Lesions ◽  
Baseline Group ◽  
Density Lipoprotein Receptor ◽  
Β Carotene

Abstract Objectives To study the effect of β-carotene on atherosclerosis regression. Methods Wild-type mice fed a Western diet (0.3% cholesterol + 41% fat) deficient in vitamin A (WD-VAD) were injected weekly with an antisense oligonucleotide targeting the low-density lipoprotein receptor (LDLR ASO) for 16 weeks. LDLR ASO is a generous gift from Ionis Pharmaceuticals. As a result, we transiently blocked LDLR expression to facilitate the development of atherosclerotic lesions. After this period, we harvested a subset of mice (baseline group), while the remaining mice underwent atherosclerosis regression by interrupting LDLR ASO injections. To study the role of β-carotene on atherosclerosis regression, we maintained a subset of mice on WD-VAD while the remaining mice were fed WD-VAD supplemented with 50 mg/kg of β-carotene (WD-β-carotene) for 3 weeks before sacrifice. Plasma and aortic roots were collected and analyzed to study the size and composition of atherosclerotic lesions. Results Baseline mice showed a 96% (P &lt; 0.0005) reduction in LDLR hepatic expression accompanied by a 3 fold (P &lt; 0.0001) increased in plasma total cholesterol in comparison to both regression groups. Histological analyses of aortic roots failed to show differences in atherosclerotic lesion area between groups, although we observed a reduction in macrophage content in both regression groups that was more pronounced in WD-β-carotene-fed mice; baseline vs WD-VAD (∼30% P &lt; 0.05), and baseline vs WD-β-carotene (∼42%, P &lt; 0.005). Collagen content in plaques, an indicator of plaque stability in humans, showed an increase in both regression groups; baseline vs WD-VAD (∼217% P &lt; 0.005), and baseline vs WD-β-carotene (∼308%, P &lt; 0.0001). Conclusions β-carotene enhances atherosclerosis resolution by decreasing the inflammation and increasing plaque stability in mice. Funding Sources NIH (R01HL147252), USDA (W4002), and margin of excellence-Division of Nutritional Sciences -UIUC.

IgG1 phosphorylcholine ameliorates plaque stability via reduced intraplaque angiogenesis and intraplaque haemorrhage in a murine atherosclerosis model

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M De Vries ◽  
F Baganha ◽  
R.C.M De Jong ◽  
H.A.B Peters ◽  
K Petterson ◽  
...  
Keyword(s):  
Vein Graft ◽  
Medical Center ◽  
Animal Experiments ◽  
Atherosclerotic Lesion ◽  
Inflammatory Cells ◽  
Intraplaque Hemorrhage ◽  
Funding Source ◽  
Plaque Stability

Abstract Background Phosphorylcholine, (PC) the polar headgroup of the dominating membrane phospholipid phosphatidylcholine, is one of the main oxLDL epitopes and an important pro-inflammatory damage associated molecular pattern. Experimental and epidemiologic data show that natural anti-PC IgM protect against cardiovascular disease. Within atherosclerotic lesions, inflammatory and angiogenesis processes are interdependent and contribute to plaque destabilization. Atherosclerotic lesion resident CD163+ macrophages promote leukocyte infiltration but also induce angiogenesis and vessel permeability by secreting VEGFA. PC antibodies are recognized for their anti-inflammatory properties. However, the effect of PC antibodies on intraplaque angiogenesis (IPA) and intraplaque hemorrhage (IPH), the main entrance route for inflammatory cells in advanced lesions, is unknown. Purpose To investigate the therapeutic effect of a new IgG1 PC antibody (PCmAB) on lesion development, IPA and IPH in murine vein graft atherosclerosis. Methods All animal experiments were performed in compliance with Dutch government guidelines and the Directive 2010/63/EU of the European Parliament. Hypercholesterolemic male ApoE3*Leiden mice received a (donor) caval vein interposition in the carotid artery. Mice received weekly ip injections of (5mg/kg) PCmAb (n=11) or vehicle (n=12) until sacrifice at day 28. Immunohistochemistry was used to evaluate vein graft morphometry and lesion composition including IPA and IPH. PCmAB isolated effects on pro-angiogenic and pro-inflammatory behaviour was investigated in vitro in HUVECs and Hemoglobin (Hb):Haptoglobin (Hp)-cultured THP-1 macrophages. Results PCmAB treatment decreased vein graft media area (13%) and intima lesion (25%), but more importantly increased lumen area with 53% when compared to vehicle treatment. PCmAb improved lesion stability by increasing collagen content (18%) and by decreasing macrophages presence (31%). VCAM-1 and ICAM-1 expression in the vessel wall were also reduced (resp.29% and 36%) by PCmAb. PCmAb improved IPA by a significant reduction in neovessel density of 34%. This was supported in vitro by significant reduced EC proliferation and migration upon PCmAB with and without oxLDL stimulation. Moreover, PCmAb enhanced maturation of intraplaque angiogenic vessels by increasing neovessel pericyte coverage in vivo (31%). Together, this resulted in a reduction of IPH of 62% in the PCmAB group. PCmAb resulted in decreased macrophages CD163+ content in vein grafts by 23% whereas CD163 expression was reduced by PCmAb in Hb:Hp stimulated macrophages. Conclusion PCmAB is an effective inhibitor of atherosclerotic lesion formation in ApoE3*Leiden mice. PCmAb reduces IPA and IPH by decreased neovessel density and (CD163+) macrophages influx via reduced expression of VCAM-1 and ICAM-1, and increased neovessel maturation in vein graft atherosclerosis. PCmAB holds a promise as a new therapeutic approach for plaque stability. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Leiden University Medical Center

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