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Annika Lindskog Jonsson, Robert Caesar, Rozita Akrami, Christoph Reinhardt, Frida Fåk Hållenius, Jan Borén, Fredrik Bäckhed
OBJECTIVE: To investigate the effect of gut microbiota and diet on atherogenesis. APPROACH AND RESULTS: Here, we investigated the interaction between the gut microbiota and diet on atherosclerosis by feeding germ-free or conventionally raised Apoe-/- mice chow or Western diet alone or supplemented with choline (which is metabolized by the gut microbiota and host enzymes to trimethylamine N-oxide) for 12 weeks. We observed smaller aortic lesions and lower plasma cholesterol levels in conventionally raised mice compared with germ-free mice on a chow diet; these differences were not observed in mice on a Western diet...
June 14, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Byambasuren Ganbaatar, Daiju Fukuda, Hotimah Masdan Salim, Sachiko Nishimoto, Kimie Tanaka, Yasutomi Higashikuni, Yoichiro Hirata, Shusuke Yagi, Takeshi Soeki, Masataka Sata
BACKGROUND AND AIMS: Ticagrelor reduces cardiovascular events in patients with acute coronary syndrome (ACS). Recent studies demonstrated the expression of P2Y12 on vascular cells including endothelial cells, as well as platelets, and suggested its contribution to atherogenesis. We investigated whether ticagrelor attenuates vascular dysfunction and inhibits atherogenesis in apolipoprotein E-deficient (apoe-/- ) mice. METHODS: Eight-week-old male apoe-/- mice were fed a western-type diet (WTD) supplemented with 0...
May 31, 2018: Atherosclerosis
Ahmad Farooq Alsayed Hasanain, Khalid M El-Maghraby, Ali A H Zayed, Amany M A Nafee, Sherif M Abdel-Aal, Sally M Bakkar
Background: The activation of the cell-mediated immune responses by Mycobacterium tuberculosis can promote atherogenesis. Aims: The aim of this study is to determine the frequency of latent tuberculosis infection (LTBI) among patients with coronary artery stenosis (CAS) and to explore the association between LTBI and development of CAS. We conducted a case-control study which included 183 patients' who underwent percutaneous coronary angiography (121 patients with CAS and 62 patients without as a control group)...
April 2018: International Journal of Mycobacteriology
Seyed Mostafa Parizadeh, Maryam Ghandehari, Motahareh Heydari-Majd, Sima Seifi, Ramin Mardani, Seyed Mohamahdreza Parizadeh, Majid Ghayour-Mobarhan, Gordon A Ferns, Seyed Mahdi Hassanian, Amir Avan
Cardiovascular disease (CVD) is one of the most important causes of morbidity and mortality, and associated with an important economic burden globally. Over the last decade, the prevalence of CVD has been rising globally, and is now associated with millions of death annually in both developed and developing countries. There is good evidence that the immune system is involved in the pathophysiology of CVD. Toll-like receptors (TLRs) and their down-stream signaling pathways play an important role in the immune system...
June 13, 2018: Current Pharmaceutical Design
Ji-Fang Guo, Yu Zhang, Qing-Xia Zheng, Yao Zhang, Hui-Hua Zhou, Lun-Meng Cui
Bioinformatics indicate that miR-223 regulates many genes associated with cholesterol metabolism, and it could also control high-density lipoprotein-cholesterol (HDL-C) uptake. As reported in previous study, miR-223 was found to be upregulated from human subjects with familial hypercholesterolaemia, however, it remains to be determined using a larger group of coronary heart disease (CHD) patients. Moreover, whether it correlates with severity of atherogenesis, has never been elucidated before. We aim to further explore the association between circulating miR-223 content and severity of CHD...
June 10, 2018: Scandinavian Journal of Clinical and Laboratory Investigation
Dorrin Zarrin Khat, Mansoor Husain
PURPOSE OF REVIEW: In addition to their effects on glycemic control, two specific classes of relatively new anti-diabetic drugs, namely the sodium glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have demonstrated reduced rates of major adverse cardiovascular events (MACE) in subjects with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). This review summarizes recent experimental results that inform putative molecular mechanisms underlying these benefits...
June 9, 2018: Current Diabetes Reports
Lingyu Zhang, Tiantian Zhang, Lin Ding, Jie Xu, Changhu Xue, Teruyoshi Yanagita, Yaoguang Chang, Yuming Wang
SCOPE: Cerebroside is an active component extracted from sea cucumber (SCC), which is a traditional tonic food in China. In this study, we investigated the protective effect of SCC on atherogenesis and determined the possible underlying mechanism. METHOD AND RESULTS: Male C57BL/6J obese mice were firstly used to explore the impact of SCC at different doses on alleviating lipid disorders and insulin sensitivity. Then ApoE-/- mice were used to evaluate the protective activities of SCC on atherosclerosis...
June 8, 2018: Molecular Nutrition & Food Research
Monique C Suarez-Giron, Anabel Castro-Grattoni, Marta Torres, Ramon Farré, Ferran Barbé, Manuel Sánchez-de-la-Torre, David Gozal, Cesar Picado, Josep M Montserrat, Isaac Almendros
Study objectives: Chronic intermittent hypoxia (CIH), a hallmark feature of obstructive sleep apnea (OSA), induces accelerated atherogenesis as well as aorta vascular remodeling. Although the cyclooxygenase (COX) pathway has been proposed to contribute to the cardiovascular consequences of OSA, the potential benefits of a widely employed COX-inhibitor such (acetylsalicylic acid, ASA) on CIH-induced vascular pathology are unknown. Therefore, we hypothesized that a common non-selective COX inhibitor such as ASA would attenuate the aortic remodeling induced by CIH in mice...
2018: Frontiers in Physiology
Alena Grebe, Florian Hoss, Eicke Latz
Inflammation is an important driver of atherosclerosis, the underlying pathology of cardiovascular diseases. Therefore, therapeutic targeting of inflammatory pathways is suggested to improve cardiovascular outcomes in patients with cardiovascular diseases. This concept was recently proven by CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study), which demonstrated the therapeutic potential of the monoclonal IL (interleukin)-1β-neutralizing antibody canakinumab. IL-1β and other IL-1 family cytokines are important vascular and systemic inflammatory mediators, which contribute to atherogenesis...
June 8, 2018: Circulation Research
Urszula Kolakowska, Elzbieta Kuroczycka-Saniutycz, Witold Olanski, Anna Wasilewska
PURPOSE: The emerging evidence has recently shown an evident dependence between recently identified salusin peptides and atherosclerosis, and their important roles as endogenous modulators of atherogenesis. It was reported that the development of atherosclerosis could be also affected by endogenous salusin- β overproduction in vascular lesions. MATERIALS/METHODS: This prospective cohort study was conducted in two groups of children: HT - 58 patients with essential hypertension (HT); R - 30 participants with white-coat HT (R)...
June 7, 2018: Current Pharmaceutical Design
Jessica M Johnston, Sheila E Francis, Endre Kiss-Toth
Background: Murine models of atherosclerosis have been invaluable to gain mechanistic understanding of this chronic disease. Induction of atherosclerosis with relative ease in ApoE-/- and Ldlr-/- mice fed a Western-type diet to cause hyperlipidaemia has provided researchers with popular tools to manipulate and characterise the action of genes that affect atherogenesis. Seminal studies and reviews have discussed key phenotypic differences between different models and "target levels of hyperlipidaemia" have also been published...
June 5, 2018: Cardiovascular Research
Niki Katsiki, Dimitri P Mikhailidis, Maciej Banach
Leptin, an adipokine that is implicated in the control of food intake via appetite suppression, may also stimulate oxidative stress, inflammation, thrombosis, arterial stiffness, angiogenesis and atherogenesis. These leptin-induced effects may predispose to the development of cardiovascular diseases. In the present review we discuss the evidence linking leptin levels with the presence, severity and/or prognosis of both coronary artery disease and non-cardiac vascular diseases such as stroke, carotid artery disease, peripheral artery disease (PAD) and abdominal aortic aneurysms (AAA) as well as with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM)...
June 7, 2018: Acta Pharmacologica Sinica
Xuchu Que, Ming-Yow Hung, Calvin Yeang, Ayelet Gonen, Thomas A Prohaska, Xiaoli Sun, Cody Diehl, Antti Määttä, Dalia E Gaddis, Karen Bowden, Jennifer Pattison, Jeffrey G MacDonald, Seppo Ylä-Herttuala, Pamela L Mellon, Catherine C Hedrick, Klaus Ley, Yury I Miller, Christopher K Glass, Kirk L Peterson, Christoph J Binder, Sotirios Tsimikas, Joseph L Witztum
Oxidized phospholipids (OxPL) are ubiquitous, are formed in many inflammatory tissues, including atherosclerotic lesions, and frequently mediate proinflammatory changes 1 . Because OxPL are mostly the products of non-enzymatic lipid peroxidation, mechanisms to specifically neutralize them are unavailable and their roles in vivo are largely unknown. We previously cloned the IgM natural antibody E06, which binds to the phosphocholine headgroup of OxPL, and blocks the uptake of oxidized low-density lipoprotein (OxLDL) by macrophages and inhibits the proinflammatory properties of OxPL2-4 ...
June 6, 2018: Nature
Catherine A Reardon, Amulya Lingaraju, Kelly Q Schoenfelt, Guolin Zhou, Chang Cui, Hannah Jacobs-El, Ilona Babenko, Andrew Hoofnagle, Daniel Czyz, Howard Shuman, Tomas Vaisar, Lev Becker
Type 2 diabetes (T2D) is associated with increased risk for atherosclerosis; however, the mechanisms underlying this relationship are poorly understood. Macrophages, which are activated in T2D and causatively linked to atherogenesis, are an attractive mechanistic link. Here, we use proteomics to show that diet-induced obesity and insulin resistance (obesity/IR) modulate a pro-atherogenic "macrophage-sterol-responsive-network" (MSRN), which, in turn, predisposes macrophages to cholesterol accumulation...
June 5, 2018: Cell Reports
Junmei Chen, Dominic W Chung
There is increasing evidence that inflammation can cause thrombosis by a von Willebrand factor (VWF)-mediated mechanism that includes endothelial activation, secretion of VWF, assembly of hyperadhesive VWF strings and fibers, cleavage by ADAMTS13, adhesion and deposition of VWF-platelet thrombi in the vasculature. This mechanism appears to contribute to thrombosis not only in small vessels, but large vessels as well. Inflammation and VWF contributes to atherogenesis and may contribute to arterial and venous thrombosis, and stroke...
June 4, 2018: Blood
Naoya Sakamoto, Yosuke Ueki, Masaki Oi, Takuya Kiuchi, Masaaki Sato
The adhesion and migration of leukocytes to arterial endothelial cells (ECs), one of the indicators of early atherogenesis, is believed to be correlated with the blood flow conditions and interactions between vascular cells including vascular smooth muscle cells (SMCs). In this study, we investigated the effect of fluid shear stress on the transendothelial migration of leukocytes in a coculture model (CM) composed of human umbilical ECs and SMCs, a layer of collagen type I, and a porous membrane. Following exposure to a fluid shear stress of 1...
May 28, 2018: Biochemical and Biophysical Research Communications
Pei-Ling Hsu, Yung-Ching Lin, Hao Ni, Fan-E Mo
Ganoderma mushrooms, used in traditional Chinese medicine to promote health and longevity, have become widely accepted as herbal supplements. Ganoderma lucidum (GL), a commonly seen ganoderma species, is commercially cultivated under controlled conditions for more consistent chemical composition. The medicinal properties of GL are attributable to its antioxidant and anti-inflammatory activities. We intended to assess the effect of GL in atherosclerosis, an arterial condition associated with chronic oxidative stress and inflammation, using a carotid-artery-ligation mouse model...
2018: Oxidative Medicine and Cellular Longevity
Aric Huang, Sarvatit Patel, Cameron S McAlpine, Geoff H Werstuck
Cardiovascular disease (CVD) is the number one cause of global mortality and atherosclerosis is the underlying cause of most CVD. However, the molecular mechanisms by which cardiovascular risk factors promote the development of atherosclerosis are not well understood. The development of new efficient therapies to directly block or slow disease progression will require a better understanding of these mechanisms. Accumulating evidence supports a role for endoplasmic reticulum (ER) stress in all stages of the developing atherosclerotic lesion however, it was not clear how ER stress may contribute to disease progression...
May 30, 2018: International Journal of Molecular Sciences
Marcello Rattazzi, Elisabetta Faggin, Elisa Bertacco, Chiara Nardin, Leopoldo Pagliani, Mario Plebani, Francesco Cinetto, Diego Guidolin, Massimo Puato, Paolo Pauletto
INTRODUCTION: Vitamin K antagonists, such as warfarin, are known to promote arterial calcification through blockade of gamma-carboxylation of Matrix-Gla-Protein. It is currently unknown whether other oral anticoagulants such as direct inhibitors of Factor Xa can have protective effects on the progression of aortic valve calcification. AIMS: to compare the effect of warfarin and rivaroxaban on the progression of aortic valve calcification in atherosclerotic mice...
May 30, 2018: Cardiovascular Therapeutics
Julian Jehle, Benedikt Schöne, Sayeh Bagheri, Elina Avraamidou, Melina Danisch, Imke Frank, Philipp Pfeifer, Laura Bindila, Beat Lutz, Dieter Lütjohann, Andreas Zimmer, Georg Nickenig
BACKGROUND: The endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) is a known modulator of inflammation and ligand to both, pro-inflammatory cannabinoid receptor 1 (CB1) and anti-inflammatory CB2. While the role of both receptors in atherogenesis has been studied extensively, the significance of 2-AG for atherogenesis is less well characterized. METHODS: The impact of 2-AG on atherogenesis was studied in two treatment groups of ApoE-/- mice. One group received the monoacylglycerol lipase (MAGL)-inhibitor JZL184 [5 mg/kg i...
2018: PloS One
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