The role of macrophage transcriptional factor MafB in atherosclerotic plaque stability

Background: Atherosclerosis is closely associated with proliferation of the adventitial vasa vasorum, leading to the atherosclerotic plaque progression and vulnerability. In this report, we investigated the role of Ginsenoside Rb1 (Rb1) on atherosclerotic plaque stabilization and adventitial vasa vasorum (VV) along with the mechanisms involved.Methods and Results: Apolipoprotein E-deficient (ApoE−/−) mice were fed with a high-fat diet for 20 weeks, and then Ginsenoside Rb1 (50 mg/kg/d, intraperitoneal) was given for 4 weeks. Rb1 treatment significantly inhibited adventitial VV proliferation, alleviated inflammation, decreased plaque burden, and stabilized atherosclerotic plaques in apoE−/− mice. However, the beneficial effects of Rb1 on atherosclerotic lesion was attenuated by overexpression of miR-33. The analysis from atherosclerotic plaque revealed that Rb1 treatment could result in an induction of Pigment epithelium-derived factor (PEDF) expression and reduction of the miR-33 generation. Overexpression of miR-33 significantly reverted the Rb1-mediated elevation of PEDF and anti-angiogenic effect.Conclusions: Ginsenoside Rb1 attenuates plaque growth and enhances plaque stability partially through inhibiting adventitial vasa vasorum proliferation and inflammation in apoE−/− mice. The anti-angiogenic and anti-inflammation effects of Rb1 are exerted via the modulation of miR-33 and its target gene PEDF.

Download Full-text

P29 THE ROLE OF EXERCISE AND ENDOCANNABINOID SYSTEM IN ATHEROSCLEROTIC PLAQUE STABILITY – EXPERIMENTAL STUDY

Atherosclerosis Supplements ◽

10.1016/s1567-5688(10)70096-9 ◽

2010 ◽

Vol 11 (2) ◽

pp. 22-23

Author(s):

M. Katsimpoulas ◽

N. Kadoglou ◽

A. Kapelouzou ◽

P. Moustardas ◽

I. Botis ◽

...

Keyword(s):

Experimental Study ◽

Atherosclerotic Plaque ◽

Endocannabinoid System ◽

Plaque Stability

Download Full-text

Abstract 412: Apelin-13 Enhances Atherosclerotic Plaque Stability in Apoe-Deficient Mice

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.412 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Rodrigo A Fraga-Silva ◽

Hugo Seeman ◽

Fabrizio Montecucco ◽

Analina R da Silva ◽

Fabienne Burger ◽

...

Keyword(s):

Shear Stress ◽

Atherosclerotic Plaque ◽

Experimental Period ◽

Serum Levels ◽

Lesion Size ◽

Plaque Formation ◽

Atherosclerotic Plaques ◽

Plaque Stability ◽

Atherosclerosis Development

Introduction: Atherosclerosis remains one of the main cause of death worldwide and substantial efforts have been made to identify novel approaches to improve the management of this disorder. Apelin is an endogenous peptidergic family with essential role on the cardiovascular hemostasis and pathologies. Recent studies pointed out a fundamental contribution of Apelin system on atherosclerosis development; however, such reports revealed contradictory data, and to date, it is difficult to accurately define the beneficial or deleterious role of Apelin in atherosclerosis. Objective: To better understand the role of Apelin system on atherosclerosis, we aimed to investigate the actions of Apelin-13 treatment on atherosclerotic plaques composition, focusing on features of plaque vulnerability. Methods: Apolipoprotein E gene-deleted mice (n=40) were fed with western-type diet for 11 weeks. Atherosclerotic plaque formation was induced in the carotid artery by a shear stress modifier device, which exposed the vessel to distinct patterns of shear stress, resulting in plaque formation with different composition. The mice were treated with Apelin-13 (2 mg/Kg/day) or vehicle for the last 3 weeks of experimental period. Results: Apelin-13 treatment did not change atherosclerotic plaque size in the aorta, neither altered the lipid content of low shear stress and oscillatory shear stress-induced plaques in the carotid. However, Apelin-13 remarkably ameliorated plaque stability by increasing intraplaque collagen content, which was associated with a reduction of MMP-9 expression. Furthermore, Apelin decreased cell infiltration (neutrophil and macrophage) and intraplaque reactive oxygen species content. Interestingly, Apelin-13 treatment reduced total cholesterol, LDL levels and free fatty acids serum levels, while HDL, triglycerides serum levels were not significantly changed. Conclusion: Apelin-13 treatment for 3 weeks did not alter the lesion size, but significantly enhances the stable phenotype of atherosclerotic plaques and improved serum lipid profile. These results indicate that activation of Apelin system enhances plaque stability.

Download Full-text

The Role of Intimal Arterial Calcification in the Context of Atherosclerotic Plaque Stability Pietro Scicchitano1*, Andrea Marzullo2

Journal of Cytology & Histology ◽

10.4172/2157-7099.1000e111 ◽

2014 ◽

Vol 05 (03) ◽

Author(s):

Pietro Scicchitano

Keyword(s):

Atherosclerotic Plaque ◽

Arterial Calcification ◽

Plaque Stability

Download Full-text

The role of macrophage transcription factor MafB in atherosclerotic plaque stability

Atherosclerosis ◽

10.1016/j.atherosclerosis.2016.05.021 ◽

2016 ◽

Vol 250 ◽

pp. 133-143 ◽

Cited By ~ 10

Author(s):

Hiromasa Hasegawa ◽

Tetsu Watanabe ◽

Shigehiko Kato ◽

Taku Toshima ◽

Miyuki Yokoyama ◽

...

Keyword(s):

Transcription Factor ◽

Atherosclerotic Plaque ◽

Plaque Stability

Download Full-text

The Role of Inflammasomes in Atherosclerosis and Stroke Pathogenesis

Current Pharmaceutical Design ◽

10.2174/1381612826666200427084949 ◽

2020 ◽

Vol 26 (34) ◽

pp. 4234-4245

Author(s):

Deepaneeta Sarmah ◽

Aishika Datta ◽

Swapnil Raut ◽

Ankan Sarkar ◽

Birva Shah ◽

...

Keyword(s):

Atherosclerotic Plaque ◽

Treatment Strategies ◽

Cerebrovascular Diseases ◽

Cellular Injury ◽

Inflammatory Reactions ◽

Inflammatory Pathways

Inflammation is a devastating outcome of cerebrovascular diseases (CVD), namely stroke and atherosclerosis. Numerous studies over the decade have shown that inflammasomes play a role in mediating inflammatory reactions post cellular injury occurring after a stroke or a rupture of an atherosclerotic plaque. In view of this, targeting these inflammatory pathways using different pharmacological therapies may improve outcomes in patients with CVD. Here, we review the mechanisms by which inflammasomes drive the pathogenesis of stroke and atherosclerosis. Also, discussed here are the possible treatment strategies available for inhibiting inflammasomes or their up-stream/down-stream mediators.

Download Full-text

Histone Deacetylase 9 Activates IKK to Regulate Atherosclerotic Plaque Vulnerability

Circulation Research ◽

10.1161/circresaha.120.316743 ◽

2020 ◽

Vol 127 (6) ◽

pp. 811-823 ◽

Cited By ~ 4

Author(s):

Yaw Asare ◽

Thomas A. Campbell-James ◽

Yury Bokov ◽

Lydia Luya Yu ◽

Matthias Prestel ◽

...

Keyword(s):

Histone Deacetylase ◽

Atherosclerotic Plaque ◽

Association Studies ◽

Endothelial Activation ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Plaque Vulnerability ◽

Plaque Stability ◽

Genome Wide ◽

Histone Deacetylase 9

Rationale: Arterial inflammation manifested as atherosclerosis is the leading cause of mortality worldwide. Genome-wide association studies have identified a prominent role of HDAC (histone deacetylase)-9 in atherosclerosis and its clinical complications including stroke and myocardial infarction. Objective: To determine the mechanisms linking HDAC9 to these vascular pathologies and explore its therapeutic potential for atheroprotection. Methods and Results: We studied the effects of Hdac9 on features of plaque vulnerability using bone marrow reconstitution experiments and pharmacological targeting with a small molecule inhibitor in hyperlipidemic mice. We further used 2-photon and intravital microscopy to study endothelial activation and leukocyte-endothelial interactions. We show that hematopoietic Hdac9 deficiency reduces lesional macrophage content while increasing fibrous cap thickness thus conferring plaque stability. We demonstrate that HDAC9 binds to IKK (inhibitory kappa B kinase)-α and β, resulting in their deacetylation and subsequent activation, which drives inflammatory responses in both macrophages and endothelial cells. Pharmacological inhibition of HDAC9 with the class IIa HDAC inhibitor TMP195 attenuates lesion formation by reducing endothelial activation and leukocyte recruitment along with limiting proinflammatory responses in macrophages. Transcriptional profiling using RNA sequencing revealed that TMP195 downregulates key inflammatory pathways consistent with inhibitory effects on IKKβ. TMP195 mitigates the progression of established lesions and inhibits the infiltration of inflammatory cells. Moreover, TMP195 diminishes features of plaque vulnerability and thereby enhances plaque stability in advanced lesions. Ex vivo treatment of monocytes from patients with established atherosclerosis reduced the production of inflammatory cytokines including IL (interleukin)-1β and IL-6. Conclusions: Our findings identify HDAC9 as a regulator of atherosclerotic plaque stability and IKK activation thus providing a mechanistic explanation for the prominence of HDAC9 as a vascular risk locus in genome-wide association studies. Its therapeutic inhibition may provide a potent lever to alleviate vascular inflammation. Graphical Abstract: A graphical abstract is available for this article.

Download Full-text