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Genes protecting from atherosclerosis

Corinna Schmitz, Heidi Noels, Omar El Bounkari, Eva Straussfeld, Remco T A Megens, Marieke Sternkopf, Setareh Alampour-Rajabi, Christine Krammer, Pathricia V Tilstam, Norbert Gerdes, Christina Bürger, Aphrodite Kapurniotu, Richard Bucala, Joachim Jankowski, Christian Weber, Jürgen Bernhagen
The inflammatory cytokine macrophage migration-inhibitory factor (MIF) promotes atherosclerosis via lesional monocyte and T-cell recruitment. B cells have emerged as important components in atherogenesis, but the interaction between MIF and B cells in atherogenesis is unknown. Here, we investigated the atherosclerotic phenotype of Mif-gene deletion in Apoe-/- mice. Apoe-/- Mif-/- mice on a Western-diet exhibited strongly reduced atherosclerotic lesions in brachiocephalic artery (BC) and abdominal aorta compared with controls...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Miguel Fontecha-Barriuso, Diego Martin-Sanchez, Olga Ruiz-Andres, Jonay Poveda, Maria Dolores Sanchez-Niño, Lara Valiño-Rivas, Marta Ruiz-Ortega, Alberto Ortiz, Ana Belén Sanz
Epigenetics refers to heritable changes in gene expression patterns not caused by an altered nucleotide sequence, and includes non-coding RNAs and covalent modifications of DNA and histones. This review focuses on functional evidence for the involvement of DNA and histone epigenetic modifications in the pathogenesis of kidney disease and the potential therapeutic implications. There is evidence of activation of epigenetic regulatory mechanisms in acute kidney injury (AKI), chronic kidney disease (CKD) and the AKI-to-CKD transition of diverse aetiologies, including ischaemia-reperfusion injury, nephrotoxicity, ureteral obstruction, diabetes, glomerulonephritis and polycystic kidney disease...
March 9, 2018: Nephrology, Dialysis, Transplantation
Domenico Girelli, Fabiana Busti, Giacomo Marchi, Nicola Martinelli, Oliviero Olivieri
The idea of using small RNA fragments (oligonucleotides) for therapeutic purposes dates back to the 1990s, following the landmark discoveries on the mechanisms of gene silencing and RNA-interference (RNA-i). However, the first applications in medicine were hampered by difficulties in chemical stabilization and efficient delivery to target tissues. Recent advances in chemical manipulation of oligonucleotides have, at least partially, bypassed such obstacles. In particular, conjugation with ligands for specific receptors allows the selective uptake of oligonucleotides by critical cells (e...
March 1, 2018: Internal and Emergency Medicine
Guo-Qiang Yuan, Song Gao, Yong-Jian Geng, Yao-Ping Tang, Min-Juan Zheng, Harnath S Shelat, Scott Collins, Han-Jing Wu, Yi-Ling Wu
Background: Our previous studies have shown that Tongxinluo (TXL), a compound Chinese medicine, can decrease myocardial ischemia-reperfusion injury, protect capillary endothelium function, and lessen cardiac ventricle reconstitution in animal models. The aim of this study was to illuminate whether TXL can improve hypercholesterolemia-impaired heart function by protecting artery endothelial function and increasing microvascular density (MVD) in heart. Furthermore, we will explore the underlying molecular mechanism of TXL cardiovascular protection...
March 5, 2018: Chinese Medical Journal
Vana Kolovou, Angelos Tsipis, Constantinos Mihas, Niki Katsiki, Vasiliki Vartela, Maria Koutelou, Dionisia Manolopoulou, Evaggelos Leondiadis, Ioannis Iakovou, Sophie Mavrogieni, Genovefa Kolovou
Patients with left main (LM) coronary artery disease (CAD) are at the highest risk of cardiovascular events. We evaluated possible gene polymorphisms of tumor protein 53 ( TP53, rs1042522, p.Arg72Pro) that can differentiate LM-CAD from patients with more peripheral CAD (MP-CAD) and healthy participants (control group) in 520 individuals (LM-CAD, n = 175; MP-CAD, n = 185; and control group, n = 160). Patients with LM-CAD had the lowest Arg/Arg genotype frequency (36.0%) compared with the MP-CAD (57.3%) and control groups (61...
January 1, 2018: Angiology
Xiao-Bing Cui, Jun-Na Luan, Kun Dong, Sisi Chen, Yongyi Wang, Wendy T Watford, Shi-You Chen
OBJECTIVE: The objective of this study is to determine the role and underlying mechanisms of RGC-32 (response gene to complement 32 protein) in atherogenesis. APPROACH AND RESULTS: RGC-32 was mainly expressed in endothelial cells of atherosclerotic lesions in both ApoE -/- (apolipoprotein E deficient) mice and human patients. RGC-32 deficiency (Rgc32 -/- ) attenuated the high-fat diet-induced and spontaneously developed atherosclerotic lesions in ApoE -/- mice without affecting serum cholesterol concentration...
February 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Fabienne Billiard, Sevasti Karaliota, Bei Wang, Dimitrios Stellas, Ioannis Serafimidis, Antigoni Manousopoulou, Yiassemi Koutmani, Elpiniki Ninou, Jacquelynn Golubov, Amanda DaNave, Panagiotis Tsakanikas, Yurong Xin, Wen Zhang, Matthew Sleeman, George D Yancopoulos, Andrew J Murphy, Spiros D Garbis, Katia Karalis, Dimitris Skokos
Although Notch signaling has been proposed as a therapeutic target for type-2 diabetes, liver steatosis, and atherosclerosis, its direct effect on pancreatic islets remains unknown. Here, we demonstrated a function of Dll4-Notch signaling inhibition on the biology of insulin-producing cells. We confirmed enhanced expression of key Notch signaling genes in purified pancreatic islets from diabetic NOD mice and showed that treatment with anti-Dll4 antibody specifically abolished Notch signaling pathway activation...
January 23, 2018: Cell Reports
Xiang Ding, Yong He, Qiukui Hao, Shanping Chen, Ming Yang, Sean X Leng, Jirong Yue, Birong Dong
Accumulated evidence has indicated that ataxia telangiectasia mutated (ATM) is closely related to atherosclerosis and cardiovascular diseases. So we aimed to examine potential association between a gene variant [single nucleotide polymorphisms (SNPs), i.e., rs189037C>T] in the promoter of ATM gene and coronary artery disease (CAD) in Chinese Han populations.In this hospital-based case-control study, a total of 1308 participants were divided into CAD group (652 patients) and control group (656 subjects) after performing coronary angiography...
January 2018: Medicine (Baltimore)
Gauri Liyakat Ali, Suman Kapur, Sai Chinmayi, Qadir Fatima, Harshal Pise, Asim Khan, Ambreen Liyakat, V Jilova, Urvashi Dube
Introduction: Dyslipidemia has been reported to attribute to early death due to increased atherosclerosis leading to CVDs in patients with RA. Recent reports have suggested a role of adipocytokines in mediating joint damage rheumatoid arthritis (RA). RA has long been associated with increased cardiovascular risk as atherosclerosis is more prevalent in patients of RA than in the general population. Specific alleles of APOE gene have been reported to be associated with risk for atherosclerosis and LEP gene alleles have been associated with increased BMI...
September 2017: Journal of the Association of Physicians of India
Maryam Tanhapour, Ali Miri, Asad Vaisi-Raygani, Fariborz Bahrehmand, Amir Kiani, Zohreh Rahimi, Tayebeh Pourmotabbed, Ebrahim Shakiba
Evidences indicate that abnormal lipid metabolism and lipid peroxidation can affect the progression of complications in systemic lupus erythematosus (SLE) patients. Apolipoprotein E (ApoE) and paraoxonase-1 (PON1) play important role in lipid metabolism and protection of lipid peroxidation. The polymorphisms of ApoE and paraoxonase (PON1) L55M (Met < Leu) allele genes lead to disorders in lipid metabolism and are related to atherosclerosis. This study is the first investigation to examine the possible association between ApoE and PON1-L55M polymorphisms and correlation with serum arylesterase (ARE) activities of PON, levels of malondialdehyde (MDA), neopterin, and lipid lipoprotein in SLE patients from Iranian western population...
December 22, 2017: Clinical Rheumatology
Leticia Gonzalez, Alexander S Qian, Usama Tahir, Pei Yu, Bernardo L Trigatti
We generated myeloid specific sphingosine-1-phosphate receptor 1 (S1pr1) deficient mice by crossing mice that had myeloid specific expression of Cre recombinase (lyzMCre) with mice having the S1pr1 gene flanked by loxP recombination sites. We transplanted bone marrow from these mice and control lyzMCre mice with intact macrophage S1pr1 gene expression into low-density lipoprotein (LDL) receptor gene (Ldlr) deficient mice. The resulting chimeras were fed a high fat atherogenic diet for nine or twelve weeks and evaluated for atherosclerosis development in the aortic sinus...
December 15, 2017: International Journal of Molecular Sciences
Juan Juan, Xia Jiang, Xun Tang, Yiqun Wu, Kexin Sun, Xiao Xiang, Yaohua Tian, Tao Wu, Qi Sun, Peter Kraft, Yonghua Hu
Paraoxonase 1 gene ( PON1 ) polymorphisms and dietary vegetable and fruit intake are both established determinants of ischemic stroke (IS). However, little is known about whether these factors jointly influence the risk of IS. We analyzed the main effects of PON1 , as well as the interactions between PON1 and dietary vegetable or fruit intake with the risk of total IS and its subtypes in a family-based case-control study conducted among 2158 Chinese participants (1007 IS cases and 1151 IS-free controls) from 918 families...
December 7, 2017: International Journal of Molecular Sciences
Hong Zhong, Ke Chen, Mengyang Feng, Wei Shao, Jun Wu, Kun Chen, Tingming Liang, Chang Liu
Hyperlipidemia is a chronic disorder which plays an important role in the development of cardiovascular diseases, type 2 diabetes, atherosclerosis, hypertension, and nonalcoholic fatty liver disease. Genipin (GNP) is a metabolite from genipioside, which is an active component of the traditional Chinese medicine Gardenia jasminoides Ellis, and has been recognized as a beneficial compound against metabolic disorders. However, whether it can correct overnutrition-induced dyslipidemia is still unknown. In this study, the effects of GNP on attenuating hyperlipidemia and hepatic lipid accumulation were investigated using normal and obese mice induced with a high-fat diet (HFD) and primary hepatocytes treated with free fatty acids...
February 2018: FEBS Journal
H Milionis
No abstract text is available yet for this article.
February 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Qin M Chen, Anthony J Maltagliati
The NFE2L2 gene encodes the transcription factor Nrf2 best known for regulating the expression of antioxidant and detoxification genes. Gene knockout approaches have demonstrated its universal cytoprotective features. While Nrf2 has been the topic of intensive research in cancer biology since its discovery in 1994, understanding the role of Nrf2 in cardiovascular disease has just begun. The literature concerning Nrf2 in experimental models of atherosclerosis, ischemia, reperfusion, cardiac hypertrophy, heart failure, and diabetes supports its cardiac protective character...
February 1, 2018: Physiological Genomics
Saranya Ravi, Robert N Schuck, Eleanor Hilliard, Craig R Lee, Xuming Dai, Kaitlin Lenhart, Monte S Willis, Brian C Jensen, George A Stouffer, Cam Patterson, Jonathan C Schisler
Our goal was to measure the association of CXCL5 and molecular phenotypes associated with coronary atherosclerosis severity in patients at least 65 years old. CXCL5 is classically defined as a proinflammatory chemokine, but its role in chronic inflammatory diseases, such as coronary atherosclerosis, is not well defined. We enrolled individuals who were at least 65 years old and undergoing diagnostic cardiac catheterization. Coronary artery disease (CAD) severity was quantified in each subject via coronary angiography by calculating a CAD score...
December 2017: American Journal of Pathology
Bradley K Wacker, Nagadhara Dronadula, Lianxiang Bi, Alexis Stamatikos, David A Dichek
OBJECTIVE: Gene therapy that expresses apo A-I (apolipoprotein A-I) from vascular wall cells has promise for preventing and reversing atherosclerosis. Previously, we reported that transduction of carotid artery endothelial cells with a helper-dependent adenoviral (HDAd) vector expressing apo A-I reduced early (4 weeks) fatty streak development in fat-fed rabbits. Here, we tested whether the same HDAd could provide long-term protection against development of more complex lesions. APPROACH AND RESULTS: Fat-fed rabbits (n=25) underwent bilateral carotid artery gene transfer, with their left and right common carotids randomized to receive either a control vector (HDAdNull) or an apo A-I-expressing vector (HDAdApoAI)...
November 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
Joanna Iwanicka, Tomasz Iwanicki, Paweł Niemiec, Tomasz Nowak, Jolanta Krauze, Władysław Grzeszczak, Sylwia Górczyńska-Kosiorz, Anna Ochalska-Tyka, Iwona Żak
Paraoxonase-1 (PON1) is the antioxidant marker of high-density lipoproteins protecting against atherosclerosis and coronary artery disease (CAD) phenotype. The purpose of the present study was to determine whether the PON1 gene rs854560 polymorphism (163T>A) is associated with CAD in Polish population. rs854560 was genotyped in 494 subjects: 248 patients with premature CAD and 246 blood donors as a control. We found that the risk of CAD was significantly higher in TT homozygotes than in A allele carriers (OR = 1...
2017: Disease Markers
Peng Liu, Jianfang Su, Xixi Song, Shixiao Wang
Vascular smooth muscle cells (VSMCs) exhibit a notably increased rate of migration, which is one of the most common pathological changes in atherosclerosis. Investigations into the role of micro (mi)RNAs in the regulation of VSMC migration are beginning to emerge and additional miRNAs involved in VSMC migration modulation require identification. In the current study, VSMCs were primarily cultured from rat thoracic aortas, transfected with miR‑92a mimics and induced by hydrogen peroxide (H2O2) for 24 h. Total mRNA and protein were collected for quantitative polymerase chain reaction and western blot analysis...
January 2018: Molecular Medicine Reports
Jacques Genest, Hong Y Choi
PURPOSE OF REVIEW: High-density lipoproteins (HDL) are thought to exert a protective role against atherosclerosis. The measurement of the cholesterol mass within HDL (HDL-C) represents a good biomarker of cardiovascular health, but HDL-C appears to be a poor therapeutic target. Here, we discuss new targets for the development of HDL-directed therapies. RECENT FINDINGS: Among cardio-protective functions of HDL particles, the ability of HDL to remove cholesterol from cells involved in the early stages of atherosclerosis is considered one of the most important functions...
November 4, 2017: Current Atherosclerosis Reports
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