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Arteriosclerosis, Thrombosis, and Vascular Biology

Arjun Majithia, Deepak L Bhatt
Antiplatelet therapies are an essential tool to reduce the risk of developing clinically apparent atherothrombotic disease and are a mainstay in the therapy of patients who have established cardiovascular, cerebrovascular, and peripheral artery disease. Strategies to intensify antiplatelet regimens are limited by concomitant increases in clinically significant bleeding. The development of novel antiplatelet therapies targeting additional receptor and signaling pathways, with a focus on maintaining antiplatelet efficacy while preserving hemostasis, hold tremendous potential to improve outcomes among patients with atherothrombotic diseases...
February 14, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Melissa D Klein, Alexis K Williams, Craig R Lee, George A Stouffer
Current guidelines recommend dual antiplatelet therapy-a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin-for patients undergoing percutaneous coronary intervention. Although clopidogrel is the most commonly prescribed P2Y12 inhibitor, it is associated with an increased risk of major adverse cardiovascular events in patients carrying loss-of-function CYP2C19 alleles. In contrast, CYP2C19 genotype does not impact clinical response to prasugrel or ticagrelor. Nevertheless, routine implementation of CYP2C19 genotyping to guide antiplatelet therapy selection has remained controversial because of the lack of large randomized controlled trials evaluating this strategy...
February 14, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Reza Hajhosseiny, Tamanna S Bahaei, Claudia Prieto, René M Botnar
Atherosclerosis is the leading cause of cardiovascular morbidity and mortality. Over the past 2 decades, increasing research attention is converging on the early detection and monitoring of atherosclerotic plaque. Among several invasive and noninvasive imaging modalities, magnetic resonance imaging (MRI) is emerging as a promising option. Advantages include its versatility, excellent soft tissue contrast for plaque characterization and lack of ionizing radiation. In this review, we will explore the recent advances in multicontrast and multiparametric imaging sequences that are bringing the aspiration of simultaneous arterial lumen, vessel wall, and plaque characterization closer to clinical feasibility...
February 14, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
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No abstract text is available yet for this article.
February 14, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Frank M Davis, Katherine Gallagher
Cardiometabolic and vascular disease, with their associated secondary complications, are the leading cause of morbidity and mortality in Western society. Chronic inflammation is a common theme that underlies initiation and progression of cardiovascular disease. In this regard, monocytes/macrophages are key players in the development of a chronic inflammatory state. Over the past decade, epigenetic modifications, such as DNA methylation and posttranslational histone processing, have emerged as important regulators of immune cell phenotypes...
February 14, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Heidi Noels, Christian Weber, Rory R Koenen
With the incidence and impact of atherosclerotic cardiovascular disease and its clinical manifestations still rising, therapeutic options that target the causal mechanisms of this disorder are highly desired. Since the CANTOS trial has demonstrated that lowering inflammation can be beneficial, focusing on mechanisms underlying inflammation, for example, leukocyte recruitment, is feasible. Being key orchestrators of leukocyte trafficking, chemokines have not lost their attractiveness as therapeutic targets, despite the difficult road to drug approval thus far...
February 14, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Michael S Garshick, Tessa Barrett, Todd Wechter, Sarah Azarchi, Jose Scher, Andrea Neimann, Stuart Katz, Judilyn Fuentes-Duculan, Maria V Cannizzaro, Sanja Jelic, Edward A Fisher, James G Krueger, Jeffrey S Berger
Objective- Psoriasis is an inflammatory skin disease which heightens the risk of cardiovascular disease. This study directly investigated vascular endothelial health and systemically altered pathways in psoriasis and matched controls. Approach and Results- Twenty patients (mean age, 40 years; 50% male) with active psoriasis and 10 age-, sex-matched controls were recruited. To investigate systemically alerted pathways, a deep sequencing omics approach was applied, including unbiased blood transcriptomic and targeted proteomic analysis...
February 14, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Alan Daugherty
No abstract text is available yet for this article.
February 14, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Raja Chakraborty, Fatima Zahra Saddouk, Ana Catarina Carrao, Diane S Krause, Daniel M Greif, Kathleen A Martin
Smooth muscle cells (SMCs) are a critical component of blood vessel walls that provide structural support, regulate vascular tone, and allow for vascular remodeling. These cells also exhibit a remarkable plasticity that contributes to vascular growth and repair but also to cardiovascular pathologies, including atherosclerosis, intimal hyperplasia and restenosis, aneurysm, and transplant vasculopathy. Mouse models have been an important tool for the study of SMC functions. The development of smooth muscle-expressing Cre-driver lines has allowed for exciting discoveries, including recent advances revealing the diversity of phenotypes derived from mature SMC transdifferentiation in vivo using inducible CreER T2 lines...
February 7, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Yu-Chuan Lin, Yen-Chun Ko, Shang-Cheng Hung, Ying-Ting Lin, Jia-Hau Lee, Ju-Ying Tsai, Po-Hsiung Kung, Meng-Chun Tsai, Yih-Fung Chen, Chin-Chung Wu
Objective- PAR4 (protease-activated receptor 4), one of the thrombin receptors in human platelets, has emerged as a promising target for the treatment of arterial thrombotic disease. Previous studies implied that thrombin exosite II, known as a binding site for heparin, may be involved in thrombin-induced PAR4 activation. In the present study, a heparin octasaccharide analog containing the thrombin exosite II-binding domain of heparin was chemically synthesized and investigated for anti-PAR4 effect. Approach and Results- PAR4-mediated platelet aggregation was examined using either thrombin in the presence of a PAR1 antagonist or γ-thrombin, which selectively activates PAR4...
February 7, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Christopher Papandreou, Aleix Sala-Vila, Serena Galié, Jananee Muralidharan, Ramón Estruch, Montserrat Fitó, Cristina Razquin, Dolores Corella, Emilio Ros, Juan Timiraos, Jose Lapetra, Lluis Serra-Majem, Silvia Carlos, Olga Castañer, Eva M Asensio, Jordi Salas-Salvadó, Mònica Bulló
Objective- To examine the associations between baseline levels of fatty acids in blood cell membranes and their 1-year changes with the incidence of coronary heart disease (CHD) in older adults at high cardiovascular disease risk. Approach and Results- This is a case-control study nested in the PREDIMED trial (Prevención con Dieta Mediterránea), with 136 CHD cases and 272 controls (matched on age, sex, body mass index, intervention group, and time of permanence in the study to the time event). We used gas chromatography to measure the proportion of 22 fatty acids in blood cell membranes at baseline and after 1 year...
February 7, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Zoe Shin Yee Lok, Alicia N Lyle
Inflammatory cytokines are necessary for an acute response to injury and the progressive healing process. However, when this acute response does not resolve and becomes chronic, the same proteins that once promoted healing then contribute to chronic inflammatory pathologies, such as atherosclerosis. OPN (Osteopontin) is a secreted matricellular cytokine that signals through integrin and CD44 receptors, is highly upregulated in acute and chronic inflammatory settings, and has been implicated in physiological and pathophysiologic processes...
February 7, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Brian T Steffen, George Thanassoulis, Daniel Duprez, James H Stein, Amy B Karger, Mathew C Tattersall, Joel D Kaufman, Weihua Guan, Michael Y Tsai
Objective- Lp(a) [lipoprotein(a)] is a well-described risk factor for atherosclerosis, but Lp(a)-associated risk may vary by race/ethnicity. We aimed to determine whether race/ethnicity modifies Lp(a)-related risk of carotid atherosclerotic plaque outcomes among black, white, Chinese, and Hispanic individuals. Approach and Results- Carotid plaque presence and score were assessed by ultrasonography at baseline (n=5155) and following a median 9.4 year period (n=3380) in MESA (Multi-Ethnic Study of Atherosclerosis) participants...
February 7, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Claudio Napoli, Giuditta Benincasa, Joseph Loscalzo
In pulmonary arterial hypertension (PAH), the Warburg effect (glycolytic shift) and mitochondrial fission are determinants of phenotype alterations characteristic of the disease, such as proliferation, apoptosis resistance, migration, endothelial-mesenchymal transition, and ECM (extracellular matrix) stiffness. Current therapies, focusing largely on vasodilation and antithrombotic protection, do not restore these aberrant phenotypes suggesting that additional pathways need be targeted. The multifactorial nature of PAH suggests epigenetic changes as potential determinants of vascular remodeling...
February 7, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Rabea Asleh, Andrew P Levy, Nina S Levy, Ayat Asleh, Hagit Goldenstein, Inbar Segol, Rajiv Gulati, Lilach O Lerman, Amir Lerman
Objective- Coronary endothelial dysfunction (ED) is an early stage of atherosclerosis and is associated with impaired HDL (high-density lipoprotein) function. A functional polymorphism at the Hp (haptoglobin) gene locus (rs72294371) has been associated with marked differences in HDL structure and function. We sought to determine whether Hp phenotype was associated with coronary ED and whether the amount of hemoglobin (Hb) tethered to HDL via Hp was Hp-type dependent and associated with ED. Approach and Results- Microvascular and epicardial coronary endothelial function was assessed in 338 individuals with nonobstructive coronary artery disease...
February 7, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Jianping Li, Changping Zhou, Hongbing Xu, Robert D Brook, Shengcong Liu, Tieci Yi, Yang Wang, Baihuan Feng, Mingming Zhao, Xu Wang, Qian Zhao, Jie Chen, Xiaoming Song, Tong Wang, Shuo Liu, Yi Zhang, Rongshan Wu, Jianing Gao, Bing Pan, Subramaniam Pennathur, Sanjay Rajagopalan, Yong Huo, Lemin Zheng, Wei Huang
Objective- We aimed to assess whether exposure to higher levels of ambient air pollution impairs HDL (high-density lipoprotein) function and to elucidate the underlying biological mechanisms potentially involved. Approach and Results- In the Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunction in Healthy Adults), 73 healthy adults (23.3±5.4 years) were followed-up with 4 repeated study visits in 2014 to 2016. During each visit, ambient air pollution concentrations, HDL function metrics, and parameters of inflammation and oxidative stress were measured...
January 31, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Seolhye Kim, Yoosoo Chang, Juhee Cho, Yun Soo Hong, Di Zhao, Jeonggyu Kang, Hyun-Suk Jung, Kyung Eun Yun, Eliseo Guallar, Seungho Ryu, Hocheol Shin
Objective- We examined the association of cardiovascular health (CVH) metrics with the development and progression of coronary artery calcium (CAC) among apparently healthy adults. Approach and Results- This cohort study included 65 494 men and women 30 years of age and older free of cardiovascular disease at baseline who underwent a comprehensive exam including CAC scoring. CVH metrics were defined according to the American Heart Association Life's Simple 7 metrics based on smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose...
January 31, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Mikio Takanashi, Takeshi Kimura, Chengcheng Li, Masaki Tanaka, Ako Matsuhashi, Hiroki Yoshida, Akari Noda, Pengfei Xu, Satoru Takase, Sachiko Okazaki, Yoko Iizuka, Hidetoshi Kumagai, Yuichi Ikeda, Takanari Gotoda, Manabu Takahashi, Hiroaki Yagyu, Shun Ishibashi, Toshimasa Yamauchi, Takashi Kadowaki, Guosheng Liang, Hiroaki Okazaki
Objective- APOA5 variants are strongly associated with hypertriglyceridemia, as well as increased risks of cardiovascular disease and acute pancreatitis. Hypertriglyceridemia in apo AV dysfunction often aggravates by environmental factors such as high-carbohydrate diets or aging. To date, the molecular mechanisms by which these environmental factors induce hypertriglyceridemia are poorly defined, leaving the high-risk hypertriglyceridemia condition undertreated. Previously, we reported that LXR (liver X receptor)-SREBP (sterol regulatory element-binding protein)-1c pathway regulates large-VLDL (very low-density lipoprotein) production induced by LXR agonist...
January 31, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Katalin Éva Sikura, László Potor, Tamás Szerafin, Abolfazl Zarjou, Anupam Agarwal, Paolo Arosio, Maura Poli, Zoltán Hendrik, Gábor Méhes, Melinda Oros, Niké Posta, Lívia Beke, Ibolya Fürtös, György Balla, József Balla
Objective- Calcific aortic valve disease is a prominent finding in elderly and in patients with chronic kidney disease. We investigated the potential role of iron metabolism in the pathogenesis of calcific aortic valve disease. Approach and Results- Cultured valvular interstitial cells of stenotic aortic valve with calcification from patients undergoing valve replacement exhibited significant susceptibility to mineralization/osteoblastic transdifferentiation in response to phosphate. This process was abrogated by iron via induction of H-ferritin as reflected by lowering ALP and osteocalcin secretion and preventing extracellular calcium deposition...
January 31, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Christina U Lorentz, Norah G Verbout, Michael Wallisch, Matthew W Hagen, Joseph J Shatzel, Sven R Olson, Cristina Puy, Monica T Hinds, Owen J T McCarty, David Gailani, András Gruber, Erik I Tucker
Objective- Factor XI (FXI) contributes to thrombotic disease although playing a limited role in normal hemostasis. We generated a unique, humanized anti-FXI antibody, AB023, which blocks factor XIIa-mediated FXI activation without inhibiting FXI activation by thrombin or the procoagulant function of FXIa. We sought to confirm the antithrombotic activity of AB023 in a baboon thrombosis model and to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy adult subjects. Approach and Results- In a primate model of acute vascular graft thrombosis, AB023 reduced platelet and fibrin accumulation within the grafts by >75%...
January 31, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
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