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Vascular Pharmacology

Binod Aryal, Yajaira Suárez
The endothelial lining can be viewed as the first line of defense against risk factors of vascular disease. Endothelial dysfunction is regarded as an initial event for atherogenesis since defects in vascular integrity and homeostasis are responsible for lipid infiltration and recruitment of monocytes into the vessel wall. Monocytes-turned-macrophages, which possess astounding inflammatory plasticity, perpetuate chronic inflammation and growth of atherosclerotic plaques and, are therefore central for the pathogenesis of atherosclerosis...
March 15, 2018: Vascular Pharmacology
Kaitlyn R Scacalossi, Coen van Solingen, Kathryn J Moore
Non-coding RNAs, once considered "genomic junk", are now known to play central roles in the dynamic control of transcriptional and post-transcriptional gene expression. Long non-coding RNAs (lncRNAs) are an expansive class of transcripts broadly described as greater than 200 nucleotides in length. While most lncRNAs are species-specific, their lack of conservation does not imbue a lack of function. LncRNAs have been found to regulate numerous diverse biological functions, including those central to macrophage differentiation and activation...
March 13, 2018: Vascular Pharmacology
Gabriele G Schiattarella, Rosalinda Madonna, Sophie Van Linthout, Thomas Thum, Rainer Schulz, Peter Ferdinandy, Cinzia Perrino
Vascular adaptations to either physiological or pathophysiological conditions commonly require gene expression modifications in the most represented cellular elements of the vessel wall, i.e. endothelial and smooth muscle cells. In addition to transcription factors, a number of mechanisms contribute to the regulation of gene expression in these cells including noncoding RNAs, histone and DNA modifications, collectively indicated as epigenetic modifications. Here, we summarize the state of art regarding the role of epigenetic changes in major vascular diseases, and discuss the potential diagnostic and therapeutic applications of epigenetic modulation in this context...
March 13, 2018: Vascular Pharmacology
Rogerio Nogueira Soares, Augusto Schneider, Sandra Costa Valle, Paulo Cavalheiro Schenkel
This study aimed to investigate whether the influence of CYP1A2 genotype in the blood pressure (BP) response to caffeine ingestion was affected by physical activity status and habitual caffeine consumption. Thirty-seven participants (19-50 years old) took place in the study and were categorized according to i) genotype: CYP1A2 (AA) "fast metabolizer", and CYP1A2 (AC) "slow metabolizer"; ii) physical activity level: sedentary (S) and physically active (A); and iii) caffeine consumption level: non-habitual caffeine consumer (NC) and habitual heavy caffeine consumer (C)...
March 6, 2018: Vascular Pharmacology
Rolf Schreckenberg, Klaus-Dieter Schlüter
Initially identified in the parathyroidea, the calcium sensing receptor (CaSR) is now recognized as an ubiquitously expressed receptor that exerts specific functions in multiple organs including the cardiovascular system. This review will focus on the role that CaSR plays in vascular and cardiac tissues. In the vasculature, CaSR is expressed in endothelial and smooth muscle cells. CaSR of endothelial cells participates in part to the regulation of local perfusion by linkage of CaSR activation to endothelial hyperpolarization and nitric oxide release...
March 4, 2018: Vascular Pharmacology
Jaksa Vukojevic, Marko Siroglavic, Katarina Kasnik, Tamara Kralj, Duje Stancic, Antonio Kokot, Darko Kolaric, Domagoj Drmic, Anita Zenko Sever, Ivan Barisic, Jelena Suran, Davor Bojic, Masa Hrelec Patrlj, Ivica Sjekavica, Katarina Horvat Pavlov, Tinka Vidovic, Josipa Vlainic, Mirjana Stupnisek, Sven Seiwerth, Predrag Sikiric
Rat inferior caval vein (ICV) ligation (up to the right ovarian vein (ROV)) commonly represents a recapitulation of Virchow: with ligation leading to vessel injury, stasis, thrombosis and hemodynamic changes. We revealed that BPC 157's therapy collectively attenuated or counteracted all these events and the full syndrome. METHODS: We applied BPC 157 (10 μg, 10 ng/kg) as an early regimen or as a delayed therapy. Assessment includes gross assessment by microcamera; microscopy, venography, bleeding, blood pressure, ECG, thermography, MDA and NO-level in plasma and ICV, and gene expression...
March 3, 2018: Vascular Pharmacology
Ankita Garg, Shashi Kumar Gupta, Thomas Thum
With the advent of empowering sequencing techniques over the past two decades, the scientific community has uncovered many underlying secrets of our genome. Non-coding transcripts covering a staggering 98% of our genome strongly suggest their involvement in diverse cellular pathways. A special class of non-coding RNAs (ncRNAs) namely long non-coding RNAs (lncRNAs) has garnered tremendous attention considering its implications in multiple developmental and pathophysiological processes. Accumulating evidence has established lncRNAs as robust regulators of pathways ranging from embryonic cell development to ultimate diseased phenotype...
February 23, 2018: Vascular Pharmacology
M Wesseling, T R Sakkers, S C A de Jager, G Pasterkamp, M J Goumans
Cell transdifferentiation occurs during cardiovascular development or remodeling either as a pathologic feature in the progression of disease or as a response to injury. Endothelial-to-Mesenchymal Transition (EndMT) is a process that is classified as a specialized form of Epithelial-to-Mesenchymal Transition (EMT), in which epithelial cells lose their epithelial characteristics and gain a mesenchymal phenotype. During transdifferentiation, cells lose both cell-cell contacts and their attachment to the basement membrane...
February 19, 2018: Vascular Pharmacology
P Totoson, M Pedard, C Marie, C Demougeot
While brain-derived neurotrophic factor (BDNF) was previously reported to induce relaxation of conduit artery, whether the BDNF/TrkB (tropomyosin-related kinase) pathway is involved in the tone control of resistance arteries is not known. This study investigated TrkB receptors levels/localization and the vasomotor effect of the TrkB receptor agonist LM22A-4 in isolated third-order mesenteric arteries from rats. Immunostaining revealed the presence of both full-length and truncated TrkB receptors, especially at the endothelial level...
February 19, 2018: Vascular Pharmacology
Carolina Baraldi A Restini, Alex Ismail, Ramya K Kumar, Robert Burnett, Hannah Garver, Gregory D Fink, Stephanie W Watts
Renal sympathetic activity affects blood pressure in part by increasing renovascular resistance via release of norepinephrine (NE) from sympathetic nerves onto renal arteries. Here we test the idea that adipose tissue adjacent to renal blood vessels, i.e. renal perivascular adipose tissue (RPVAT), contains a pool of NE which can be released to alter renal vascular function. RPVAT was obtained from around the main renal artery/vein of the male Sprague Dawley rats. Thoracic aortic PVAT and mesenteric PVAT also were studied as brown-like and white fat comparators respectively...
February 14, 2018: Vascular Pharmacology
Dominique Manikowski, Birgit Andrée, Esther Samper, Clémence Saint-Marc, Ruth Olmer, Peter Vogt, Sarah Strauß, Axel Haverich, Andres Hilfiker
In natural tissues, the nutrition of cells and removal of waste products is facilitated by a dense capillary network which is generated during development. This perfusion system is also indispensable for tissue formation in vitro. Nutrition depending solely on diffusion is not sufficient to generate tissues of clinically relevant dimensions, which is a core aim in tissue engineering research. In this study, the establishment of a vascular network was investigated in a self-assembling approach employing endothelial and mural cells...
February 13, 2018: Vascular Pharmacology
Meng-Hsun Yu, Ming-Cheng Lin, Chien-Ning Huang, Kuei-Chuan Chan, Chau-Jong Wang
Atherosclerosis involves the proliferation and migration of vascular smooth muscle cells (VSMCs). The migration of VSMCs from the media into the intima and their subsequent proliferation are important processes in neointima formation in atherosclerosis and restenosis after percutaneous coronary interventions. Acarbose, an alpha-glucosidase inhibitor, has been demonstrated to not affect serum levels of glucose and decrease the progression of intima-media thickening in rabbits fed with a high cholesterol diet (HCD)...
February 9, 2018: Vascular Pharmacology
Agata Hanna Bryk, Ewa Wypasek, Krzysztof Plens, Magdalena Awsiuk, Anetta Undas
INTRODUCTION: Single nucleotide polymorphisms (SNP) in genes encoding proteins involved in metabolism and action of vitamin K antagonists (VKA) affect anticoagulation stability. We investigated how those polymorphisms influence bleeding rates in patients following venous thromboembolism (VTE). MATERIALS AND METHODS: In 324 patients following unprovoked VTE, 143 (44%) on warfarin and 181 (56%) on acenocoumarol, we recorded bleedings within the preceding 24 months...
February 9, 2018: Vascular Pharmacology
Rosalinda Madonna, Damiana Pieragostino, Carmela Rita Balistreri, Claudia Rossi, Yong-Jian Geng, Piero Del Boccio, Raffaele De Caterina
Diabetic macroangiopathy - a specific form of accelerated atherosclerosis - is characterized by intra-plaque new vessel formation due to excessive/abnormal neovasculogenesis and angiogenesis, increased vascular permeability of the capillary vessels, and tissue edema, resulting in frequent atherosclerotic plaque hemorrhage and plaque rupture. Mechanisms that may explain the premature and rapidly progressive nature of atherosclerosis in diabetes are multiple, and to a large extent still unclear. However, mechanisms related to hyperglycemia certainly play an important role...
February 6, 2018: Vascular Pharmacology
Jingwei Bian, Suli Zhang, Ming Yi, MingmingYue, Huirong Liu
The internalization of angiotensin II type 1 receptor (AT 1 R) plays an important role in maintaining cardiovascular homeostasis. Decreased receptor internalization is closely related to cardiovascular diseases induced by the abnormal activation of AT 1 R, such as hypertension. However, the mechanism behind reduced AT 1 R internalization is not fully understood. This review focuses on four parts of the receptor internalization process (the combination of agonists and receptors, receptor phosphorylation, endocytosis, and recycling) and summarizes the possible mechanisms by which AT 1 R internalization is reduced based on these four parts of the process...
February 6, 2018: Vascular Pharmacology
Viorel Simion, Stefan Haemmig, Mark W Feinberg
Accumulating studies indicate that long non-coding RNAs (lncRNAs) play important roles in the regulation of diverse biological processes involved in homeostatic control of the vessel wall in health and disease. However, our knowledge of the mechanisms by which lncRNAs control gene expression and cell signaling pathways is still nascent. Furthermore, only a handful of lncRNAs has been functionally evaluated in response to pathophysiological stimuli or in vascular disease states. For example, lncRNAs may regulate endothelial dysfunction by modulating endothelial cell proliferation (e...
February 6, 2018: Vascular Pharmacology
Zhen Lu, Feng Wang, Pei Yu, Xue Wang, Yuan Wang, Song-Tao Tang, Hua-Qing Zhu
The treatment of atherosclerosis (AS), a severe condition associated with the pathogenesis of cardiovascular diseases (CVDs), is still not satisfactory worldwide. In this study, we aim to investigate whether protein sprout homologue 1 (SPRY1), a upstream mediator of MAPK signal pathway, is the target of miR-29b in vascular endothelium during the development of AS. ApoE-/- mice model was established, and an inverse correlation was noticed between level of miR-29b and SPRY1 expression in the aortic tissues. Meanwhile, the tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS) expression and NADPH oxidase activity were up-regulated in atherosclerotic tissues...
February 1, 2018: Vascular Pharmacology
Amy Leung, Vishnu Amaram, Rama Natarajan
Diabetes leads to markedly accelerated rates of many associated macrovascular complications like hypertension and atherosclerosis, and microvascular complications like nephropathy and retinopathy. High glucose, the hallmark of diabetes, drives changes in vascular and inflammatory cells that promote the development of these complications. Understanding the molecular processes involved in the development of diabetes and its debilitating complications can lead to much needed newer clinical therapies. Recently, long-noncoding RNAs (lncRNAs) have been shown to be important in the biology of vascular cells and there is growing evidence that lncRNAs are also involved in the cell biology relevant to diabetic vascular complications...
February 1, 2018: Vascular Pharmacology
Irina Sieve, Melanie Ricke-Hoch, Martina Kasten, Karin Battmer, Britta Stapel, Christine S Falk, Matthias S Leisegang, Axel Haverich, Michaela Scherr, Denise Hilfiker-Kleiner
Inflammation plays an important role in atherosclerosis, a notion supported by the beneficial effects of the IL-1β inhibitor canakinumab in the CANTOS trial. Sialic acids (Sias), components of the surface glycocalyx, regulate intercellular and intermolecular interactions. We investigated the expression of the Sia cleaving enzyme neuraminidase-1 (NEU1) in atherosclerotic plaques and its potential role in inflammatory processes. In isolated mononuclear blood cells from patients with myocardial infarction, NEU1 expression was increased compared to healthy controls...
January 22, 2018: Vascular Pharmacology
Alexander I Bondarenko, Olga Panasiuk, Konstantin Drachuk, Fabrizio Montecucco, Karim J Brandt, François Mach
Endothelium-dependent component of cannabinoid-induced vasodilation has been postulated to require G-protein-coupled non-CB1/CB2 endothelial cannabinoid (eCB) receptor. GPR18 was proposed as a candidate for eCBR. To address the hypothesis that the effects attributed to eCBR are mediated by G-protein-coupled receptor (GPCR)-independent targets, we studied the electrical responses in endothelial cells, focusing on BKCa channels. In patches excised from endothelial-derived EA.hy926 cells, N-arachydonoyl glycine (NAGly) and abnormal cannabidiol (abn-cbd), prototypical agonists for eCB receptor, stimulate single BKCa activity in a concentration- and Ca2+-dependent manner...
January 17, 2018: Vascular Pharmacology
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