Hubungan Kadar Apolipoprotein B Dengan Aterosklerosis Arteri Karotis Interna Pada Pasien Pasca Stroke Iskemik

Background: Ischemic stroke is caused by brain artery obstruction or narrowing called atherosclerosis. Its marker is the thickness of tunica intima-media (intima-media thickness / IMT) of the artery. Apolipoprotein B is the indicator of atherosclerosis diseases. Most previous studies find association between apolipoprotein B level with cardiovascular disease, while the association between apolipoprotein B with atherosclerosis in post ischemic stroke patients has not been studied yet. Objective: To investigate association between apolipoprotein B level and internal carotid artery atherosclerosis based on thickness of intima-media in patients post ischemic stroke. Method : This cross-sectional study was done in post ischemic stroke subjects in outpatient clinic of Neurology Department Kariadi Hospital Semarang, during December until February 2011. Apolipoprotein B level was measured with Integra method. The thickness of tunica intima-media of the internal carotid artery was measured by Ultrasonografi Duplex. Result: Fourty four patients post ischemic stroke that met the inclusion and exclusion criteria, comprise of 22 male (50%) and 22 female (50%). Atherosclerosis was defined as tunica intimamedia thickness >0.9 mm, was found in 24 subjects (54.6%). Apolipoprotein B level, which designated as high (apoB >105 mg/dl), was found in 25 subjects (56.8%). Multyvariat logistics regression test proved there was significant correlation between apolipoprotein B level with internal carotid artery atherosclerosis (p = 0.0001). Conclusion: Apolipoprotein B level significantly has correlation with atherosclerosis of internal carotid artery based on thickness of intima-media in patients post ischemic stroke. Key words: apolipoprotein B level, internal carotid artery atherosclerosis, ischemic stroke

Exercise and Coronary Atherosclerosis: Observations, Explanations, Relevance, and Clinical Management.

Physical activity and exercise training are effective strategies for reducing the risk of cardiovascular events, but multiple studies have reported an increased prevalence of coronary atherosclerosis, usually measured as coronary artery calcification, among athletes who are middle-aged and older. Our review of the medical literature demonstrates that the prevalence of coronary artery calcification and atherosclerotic plaques, which are strong predictors for future cardiovascular morbidity and mortality, was higher in athletes compared with controls, and was higher in the most active athletes compared with less active athletes. However, analysis of plaque morphology revealed fewer mixed plaques and more often only calcified plaques among athletes, suggesting a more benign composition of atherosclerotic plaques. This review describes the effects of physical activity and exercise training on coronary atherosclerosis in athletes who are middle-aged and older and aims to contribute to the understanding of the potential adverse effects of the highest doses of exercise training on the coronary arteries. For this purpose, we will review the association between exercise and coronary atherosclerosis measured using computed tomography, discuss the potential underlying mechanisms for exercise-induced coronary atherosclerosis, determine the clinical relevance of coronary atherosclerosis in middle-aged athletes and describe strategies for the clinical management of athletes with coronary atherosclerosis to guide physicians in clinical decision making and treatment of athletes with elevated coronary artery calcification scores

MHC class II-restricted antigen presentation by plasmacytoid dendritic cells drives proatherogenic T cell immunity

Background—Plasmacytoid dendritic cells (pDCs) bridge innate and adaptive immune responses and are important regulators of immuno-inflammatory diseases. However, their role in atherosclerosis remains elusive. Methods and Results—Here, we used genetic approaches to investigate the role of pDCs in atherosclerosis. Selective pDC deficiency in vivo was achieved using CD11c-Cre × Tcf4–/flox bone marrow transplanted into Ldlr–/– mice. Compared with control Ldlr–/– chimeric mice, CD11c-Cre × Tcf4–/flox mice had reduced atherosclerosis levels. To begin to understand the mechanisms by which pDCs regulate atherosclerosis, we studied chimeric Ldlr–/– mice with selective MHCII deficiency on pDCs. Significantly, these mice also developed reduced atherosclerosis compared with controls without reductions in pDC numbers or changes in conventional DCs. MHCII-deficient pDCs showed defective stimulation of apolipoprotein B100–specific CD4+ T cells in response to native low-density lipoprotein, whereas production of interferon-α was not affected. Finally, the atheroprotective effect of selective MHCII deficiency in pDCs was associated with significant reductions of proatherogenic T cell–derived interferon-γ and lesional T cell infiltration, and was abrogated in CD4+ T cell–depleted animals. Conclusions—This study supports a proatherogenic role for pDCs in murine atherosclerosis and identifies a critical role for MHCII-restricted antigen presentation by pDCs in driving proatherogenic T cell immunity

Apolipoprotein E and Atherosclerosis: From Lipoprotein Metabolism to MicroRNA Control of Inflammation.

Apolipoprotein (apo) E stands out among plasma apolipoproteins through its unprecedented ability to protect against atherosclerosis. Although best recognized for its ability to mediate plasma lipoprotein clearance in the liver and protect against macrophage foam cell formation, our recent understanding of the influence that apoE can exert to control atherosclerosis has significantly widened. Among apoE's newfound athero-protective properties include an ability to control exaggerated hematopoiesis, blood monocyte activation and aortic stiffening in mice with hyperlipidemia. Mechanisms responsible for these exciting new properties extend beyond apoE's ability to prevent cellular lipid excess. Rather, new findings have revealed a role for apoE in regulating microRNA-controlled cellular signaling in cells of the immune system and vascular wall. Remarkably, infusions of apoE-responsive microRNA mimics were shown to substitute for apoE in protecting against systemic and vascular inflammation to suppress atherosclerosis in mice with hyperlipidemia. Finally, more recent evidence suggests that apoE may control the release of microvesicles that could modulate cellular signaling, inflammation and atherosclerosis at a distance. These exciting new findings position apoE within the emerging field of intercellular communication that could introduce new approaches to control atherosclerosis cardiovascular disease

PRAS40 suppresses atherogenesis through inhibition of mTORC1-dependent pro-inflammatory signaling in endothelial cells

Endothelial pro-inflammatory activation plays a pivotal role in atherosclerosis, and many pro-inflammatory and atherogenic signals converge upon mechanistic target of rapamycin (mTOR). Inhibitors of mTOR complex 1 (mTORC1) reduced atherosclerosis in preclinical studies, but side effects including insulin resistance and dyslipidemia limit their clinical use in this context. Therefore, we investigated PRAS40, a cell type-specific endogenous modulator of mTORC1, as alternative target. Indeed, we previously found PRAS40 gene therapy to improve metabolic profile; however, its function in endothelial cells and its role in atherosclerosis remain unknown. Here we show that PRAS40 negatively regulates endothelial mTORC1 and pro-inflammatory signaling. Knockdown of PRAS40 in endothelial cells promoted TNFα-induced mTORC1 signaling, proliferation, upregulation of inflammatory markers and monocyte recruitment. In contrast, PRAS40-overexpression blocked mTORC1 and all measures of pro-inflammatory signaling. These effects were mimicked by pharmacological mTORC1-inhibition with torin1. In an in vivo model of atherogenic remodeling, mice with induced endothelium-specific PRAS40 deficiency showed enhanced endothelial pro-inflammatory activation as well as increased neointimal hyperplasia and atherosclerotic lesion formation. These data indicate that PRAS40 suppresses atherosclerosis via inhibition of endothelial mTORC1-mediated pro-inflammatory signaling. In conjunction with its favourable effects on metabolic homeostasis, this renders PRAS40 a potential target for the treatment of atherosclerosis

Porphyromonas gingivalis lipopolysaccharide alters atherosclerotic-related gene expression in oxidized low-density-lipoprotein-induced macrophages and foam cells

The molecular mechanism between atherosclerosis formation and periodontal pathogens is not clear although positive correlation between periodontal infections and cardiovascular diseases has been reported. Objective: To determine if atherosclerosis related genes were affected in foam cells during and after its formation by P. gingivalis lipopolysaccharide (LPS) stimulation. Methods: Macrophages from human THP-1 monocytes were treated with oxidized low density lipoprotein (oxLDL) to induce the formation of foam cells. P. gingivalis LPS was added to cultures of either oxLDL-induced macrophages or foam cells. The expression of atherosclerosis related genes was assayed by quantitative real time PCR and the protein production of granulocyte-macrophage colony-stimulating factor（GM-CSF）, monocyte chemotactic protein-1 (MCP-1), IL-1β, IL-10 and IL-12 was determined by ELISA. Nuclear translocation of NF-κB P65 was detected by immunocytochemistry and western blot was used to evaluate IKB-α degradation to confirm the NF-κB pathway activation. Results: P. gingivalis LPS stimulated atherosclerosis related gene expression in foam cells and increased oxLDL induced expression of chemokines, adhesion molecules, growth factors, apoptotic genes, and nuclear receptors in macrophages. Transcription of the pro-inflammatory cytokines IL-1β and IL-12 was elevated in response to LPS in both macrophages and foam cells, whereas the anti-inflammatory cytokine IL-10 was not affected. Increased NF-κB pathway activation was also observed in LPS and oxLDL co-stimulated macrophages. Conclusion: P. gingivalis LPS appears to be an important factor in the development of atherosclerosis by stimulation of atherosclerosis related gene expression in both macrophages and foam cells via activation of the NF-κB pathway

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

The Role of Costimulatory Receptors of the Tumour Necrosis Factor Receptor Family in Atherosclerosis

Atherosclerosis is a chronic inflammatory disease that is mediated by both the innate and adaptive immune responses. T lymphocytes, that together with B cells are the cellular effectors of the adaptive immune system, are currently endowed with crucial roles in the development and progression of atherosclerosis. Costimulatory receptors are a class of molecules expressed by T lymphocytes that regulate the activation of T cells and the generation of effector T-cell responses. In this review we present the roles of costimulatory receptors of the tumour necrosis factor receptor (TNFR) superfamily in atherosclerosis and discuss the implications for future therapies that could be used to specifically modulate the immune response of pathogenic T cells in this disease