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Microvascular Dysfunction

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https://www.readbyqxmd.com/read/28538086/sphingosine-1-phosphate-receptor-1-agonist-sew2871-causes-severe-cardiac-side-effects-and-does-not-improve-microvascular-barrier-breakdown-in-sepsis
#1
Sven Flemming, Natalie Burkard, Michael Meir, Martin Alexander Schick, Christoph-Thomas Germer, Nicolas Schlegel
BACKGROUND: Endothelial barrier dysfunction is a hallmark in the pathogenesis of sepsis. Sphingosine-1-phosphate (S1P) has been proposed to be critically involved in the maintenance of endothelial barrier function predominately by activating S1P receptor-1 (S1P1). Previous studies have shown that the specific S1P1 agonist SEW2871 improves endothelial barrier function under inflammatory conditions. However, the effectiveness of SEW2871 and potential side effects remained largely unexplored in a clinically relevant model of sepsis...
May 23, 2017: Shock
https://www.readbyqxmd.com/read/28534977/runx3-modulates-hypoxia-induced-endothelial-to-mesenchymal-transition-of-human-cardiac-microvascular-endothelial-cells
#2
Yanhua Liu, Jin Zou, Bingong Li, Yuqin Wang, Delong Wang, Yanqin Hao, Xuan Ke, Xingxing Li
Endothelial-mesenchymal transition (EndMT) is an essential mechanism in the cardiovascular system, for both cardiovascular development and cardiovascular diseases (CVDs). Recent studies indicate that runt-related transcription factor 3 (RUNX3) contributes to EndMT and endothelial cell dysfunction. However, the underlying molecular mechanism remains unknown. The present study was designed to investigate the role of RUNX3 in EndMT and endothelial cell function, and to elucidate the underlying molecular mechanism...
May 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28529513/ionizing-radiation-induced-immune-and-inflammatory-reactions-in-the-brain
#3
REVIEW
Katalin Lumniczky, Tünde Szatmári, Géza Sáfrány
Radiation-induced late brain injury consisting of vascular abnormalities, demyelination, white matter necrosis, and cognitive impairment has been described in patients subjected to cranial radiotherapy for brain tumors. Accumulating evidence suggests that various degrees of cognitive deficit can develop after much lower doses of ionizing radiation, as well. The pathophysiological mechanisms underlying these alterations are not elucidated so far. A permanent deficit in neurogenesis, chronic microvascular alterations, and blood-brain barrier dysfunctionality are considered among the main causative factors...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28528579/phosphodiesterase-type-5-inhibition-may-reduce-diastolic-function-in-women-with-ischemia-but-no-obstructive-coronary-artery-disease
#4
Michael D Nelson, Puja K Mehta, Janet Wei, Behzad Sharif, Louise E J Thomson, Daniel Berman, Debiao Li, C Noel Bairey Merz
BACKGROUND: Ischemia, in the absence of obstructive coronary artery disease, is prevalent in women, and associated with increased risk for major cardiovascular events. Coronary microvascular dysfunction is prevalent in these patients, and associated with impaired diastolic function. Despite our general understanding, however, optimal treatment of this cohort remains elusive. METHODS: To address this knowledge gap, we performed an open-label treatment trial to assess whether phosphodiesterase type 5 inhibition improves coronary microvascular perfusion and diastolic function in women with signs and symptoms of ischemia but no evidence of obstructive coronary artery disease...
May 22, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28526473/coronary-flow-reserve-is-reduced-in-sarcoidosis
#5
Seref Kul, Gonul Aciksari Kutlu, Tolga Sinan Guvenc, Murat Kavas, Kenan Demircioglu, Yusuf Yilmaz, Halil Ibrahim Yakar, Asiye Kanbay, Sibel Boga, Mustafa Caliskan
BACKGROUND AND AIMS: Sarcoidosis is a multisystem disease with frequent cardiac involvement, albeit manifest cardiac disease is rare. Though epicardial coronary arteries are not frequently involved, microvascular disease is rather common in both symptomatic and asymptomatic patients. The mechanism of microvascular involvement has not been elaborated yet. The aim of this study is to investigate coronary flow velocity reserve (CFVR) using transthoracic echocardiography in patients with sarcoidosis but without known atherosclerotic coronary artery disease or risk factors for atherosclerosis...
May 4, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28525674/continuous-hemoadsorption-with-a-cytokine-adsorber-during-sepsis-a-review-of-the-literature
#6
Khosrow S Houschyar, Malcolm N Pyles, Susanne Rein, Ina Nietzschmann, Dominik Duscher, Zeshaan N Maan, Kristian Weissenberg, Hubertus M Philipps, Catharina Strauss, Beate Reichelt, Frank Siemers
Sepsis is a well-recognized healthcare issue worldwide, ultimately resulting in significant mortality, morbidity and resource utilization during and after critical illness. In its most severe form, sepsis causes multi-organ dysfunction that produces a state of critical illness characterized by severe immune dysfunction and catabolism. Sepsis induces the activation of complement factor via 3 pathways and the release of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β), resulting in a systemic inflammatory response...
May 19, 2017: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28525354/the-relationship-between-insulin-resistance-and-endothelial-dysfunction-in-obese-adolescents
#7
Preneet Cheema Brar, Payal Patel, Stuart Katz
BACKGROUND: Insulin resistance and endothelial dysfunction share a reciprocal relationship that links the metabolic and cardiovascular sequelae of obesity. We characterized the brachial artery reactivity testing (BART) and carotid artery-intima media thickness (CIMT) in adolescents categorized as obese insulin resistant (OIR) and obese not insulin resistant (ONIR). Lipoprotein particle (p) analysis and inflammatory cytokines in OIR and ONIR groups were also analyzed. METHODS: Obese adolescents (n=40; mean body mass index [BMI] 35...
May 18, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28520942/emerging-roles-for-micrornas-in-diabetic-microvascular-disease-novel-targets-for-therapy
#8
Yu Zhang, Xinghui Sun, Basak Icli, Mark W Feinberg
Chronic, low-grade systemic inflammation and impaired microvascular function are critical hallmarks in the development of insulin resistance. Accordingly, insulin resistance is a major risk factor for type 2 diabetes and cardiovascular disease. Accumulating studies demonstrate that restoration of impaired function of the diabetic macro- and microvasculature may ameliorate a range of cardiovascular disease states and diabetes-associated complications. In this review, we focus on the emerging role of microRNAs (miRNAs), noncoding RNAs that fine-tune target gene expression and signaling pathways, in insulin-responsive tissues and cell types important for maintaining optimal vascular homeostasis and preventing the sequelae of diabetes-induced end organ injury...
April 1, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28515693/rolipram-improves-outcome-in-a-rat-model-of-infant-sepsis-induced-cardiorenal-syndrome
#9
Clark R Sims, Sharda P Singh, Shengyu Mu, Neriman Gokden, Dala Zakaria, Trung C Nguyen, Philip R Mayeux
While the mortality rate associated with sepsis in children has fallen over the years, it still remains unacceptably high. The development of both acute cardiac dysfunction and acute kidney injury during severe sepsis is categorized as type 5 cardiorenal syndrome (CRS) and is poorly understood in infants. To address this lack of understanding and the need for an appropriate animal model in which to conduct relevant preclinical studies, we developed a model of infant sepsis-induced CRS in rat pups then evaluated the therapeutic potential of the phosphodiesterase (PDE) 4 inhibitor, rolipram...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28514657/huntington-s-disease-ipsc-derived-brain-microvascular-endothelial-cells-reveal-wnt-mediated-angiogenic-and-blood-brain-barrier-deficits
#10
Ryan G Lim, Chris Quan, Andrea M Reyes-Ortiz, Sarah E Lutz, Amanda J Kedaigle, Theresa A Gipson, Jie Wu, Gad D Vatine, Jennifer Stocksdale, Malcolm S Casale, Clive N Svendsen, Ernest Fraenkel, David E Housman, Dritan Agalliu, Leslie M Thompson
Brain microvascular endothelial cells (BMECs) are an essential component of the blood-brain barrier (BBB) that shields the brain against toxins and immune cells. While BBB dysfunction exists in neurological disorders, including Huntington's disease (HD), it is not known if BMECs themselves are functionally compromised to promote BBB dysfunction. Further, the underlying mechanisms of BBB dysfunction remain elusive given limitations with mouse models and post-mortem tissue to identify primary deficits. We undertook a transcriptome and functional analysis of human induced pluripotent stem cell (iPSC)-derived BMECs (iBMEC) from HD patients or unaffected controls...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28512159/employing-extracellular-volume-cardiovascular-magnetic-resonance-measures-of-myocardial-fibrosis-to-foster-novel-therapeutics
#11
Erik B Schelbert, Hani N Sabbah, Javed Butler, Mihai Gheorghiade
Quantifying myocardial fibrosis (MF) with myocardial extracellular volume measures acquired during cardiovascular magnetic resonance promises to transform clinical care by advancing pathophysiologic understanding and fostering novel therapeutics. Extracellular volume quantifies MF by measuring the extracellular compartment depicted by the myocardial uptake of contrast relative to plasma. MF is a key domain of dysfunctional but viable myocardium among others (eg, microvascular dysfunction and cardiomyocyte/mitochondrial dysfunction)...
June 2017: Circulation. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28512048/combined-hyperactive-dysfunction-syndrome-of-the-cranial-nerves-a-retrospective-systematic-study-of-clinical-characteristics-in-44-patients
#12
Jingwei Cao, Jie Jiao, Zhenhui Du, Wenzhe Xu, Bin Sun, Feng Li, Yuguang Liu
BACKGROUND: Combined hyperactive dysfunction syndrome (HDS) is defined as the combination symptoms arising from overactivity in cranial nerves specifically, trigeminal neuralgia (TN), hemifacial spasm (HFS), and glossopharyngeal neuralgia (GPN) without an obvious explanatory structural lesion. The study aims to retrospectively analyze the clinical characteristics of combined HDS treated with microvascular decompression (MVD) in a single institution. METHODS: A total of 1450 patients with HDS were treated with MVD in our department during a 10-year period, among which 44 cases of combined HDS were identified...
May 13, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28510986/blood-pressure-normalization-via-pharmacotherapy-improves-cutaneous-microvascular-function-through-no-dependent-and-independent-mechanisms
#13
Daniel H Craighead, Caroline J Smith, Lacy M Alexander
Hypertension is associated with endothelial dysfunction and vascular remodeling. OBJECTIVE: To assess effects of antihypertensive pharmacotherapy on eNOS and iNOS-dependent mechanisms and maximal vasodilator capacity in the cutaneous microvasculature METHODS: Intradermal microdialysis fibers were placed in 15 normotensive (SBP 111±2 mmHg), 12 unmedicated hypertensive (SBP 142±2 mmHg), and 12 medicated hypertensive (SBP 120±2 mmHg) subjects. Treatments were control, iNOS-inhibited (1400w), and NOS-inhibited (L-NAME)...
May 16, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28507177/evidence-for-a-derangement-of-the-microvascular-system-in-patients-with-a-very-early-diagnosis-of-systemic-sclerosis
#14
Inês Chora, Eloisa Romano, Mirko Manetti, Celestina Mazzotta, Raquel Costa, Vera Machado, Alice Cortez, Cosimo Bruni, Gemma Lepri, Serena Guiducci, Amato De Paulis, Raquel Soares, Marco Matucci-Cerinic
OBJECTIVE: To investigate whether patients with a very early diagnosis of systemic sclerosis (VEDOSS) may already present circulating markers and in vitro signs of microvascular dysfunction. METHODS: Serum samples were obtained from 55 patients with systemic sclerosis (SSc), 25 patients with VEDOSS, and 55 matched healthy controls (HC). Serum levels of pan-vascular endothelial growth factor (VEGF) and soluble neuropilin-1 (sNRP-1) were measured by ELISA. Human dermal microvascular endothelial cells (H-MVEC) were cultured and stimulated with SSc, VEDOSS, and HC sera...
May 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28501910/targeting-the-dominant-mechanism-of-coronary-microvascular-dysfunction-with-intracoronary-physiology-tests
#15
REVIEW
Hernán Mejía-Rentería, Nina van der Hoeven, Tim P van de Hoef, Julius Heemelaar, Nicola Ryan, Amir Lerman, Niels van Royen, Javier Escaned
The coronary microcirculation plays a key role in modulating blood supply to the myocardium. Several factors like myocardial oxygen demands, endothelial and neurogenic conditions determine its function. Although there is available evidence supporting microvascular dysfunction as an important cause of myocardial ischaemia, with both prognostic and symptomatic implications, its diagnosis and management in clinical practice is still relegated to a second plane. Both diagnostic and therapeutic approaches are hampered by the broadness of the concept of microvascular dysfunction, which fails addressing the plurality of mechanisms leading to dysfunction...
May 13, 2017: International Journal of Cardiovascular Imaging
https://www.readbyqxmd.com/read/28501350/first-in-man-prolonged-pressure-controlled-intermittent-coronary-sinus-occlusion-to-treat-refractory-left-ventricular-dysfunction-and-ischemia-with-patent-epicardial-coronary-arteries
#16
Federico Pappalardo, Marco B Ancona, Francesco Giannini, Damiano Regazzoli, Antonio Mangieri, Matteo Montorfano, Michele De Bonis, Ottavio Alfieri, Alberto Zangrillo, Anna Mara Scandroglio, Antonio Colombo, Azeem Latib
AIMS: Pressure-controlled Intermittent Coronary Sinus Occlusion (PICSO) intermittently increases the pressure in the cardiac venous outflow tract using a balloon-tipped catheter introduced percutaneously into the coronary sinus. It aims to improve microvascular perfusion in STEMI patients during PCI, thus improving infarct healing. Its successful administration was associated with an improvement in myocardial recovery four months after primary-PCI as compared to control. However, it has never been used in other settings or for a prolonged period...
May 9, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28499911/aging-associated-metabolic-disorder-induces-nox2-activation-and-oxidative-damage-of-endothelial-function
#17
Lampson M Fan, Sarah Cahill-Smith, Li Geng, Junjie Du, Gavin Brooks, Jian-Mei Li
Oxidative stress attributable to the activation of a Nox2-containing NADPH oxidase is involved in the development of vascular diseases and in aging. However, the mechanism of Nox2 activation in normal aging remains unclear. In this study, we used age-matched wild-type (WT) and Nox2 knockout (KO) mice at 3-4 months (young); 11-12 months (middle-aged) and 21-22 months (aging) to investigate age-related metabolic disorders, Nox2 activation and endothelial dysfunction. Compared to young mice, middle-aged and ageing WT mice had significantly hyperglycaemia, hyperinsulinaemia, systemic oxidative stress and higher blood pressure...
May 9, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28490763/methylglyoxal-induced-glycation-changes-adipose-tissue-vascular-architecture-flow-and-expansion-leading-to-insulin-resistance
#18
Tiago Rodrigues, Paulo Matafome, José Sereno, José Almeida, João Castelhano, Luís Gamas, Christian Neves, Sónia Gonçalves, Catarina Carvalho, Amina Arslanagic, Elinor Wilcken, Rita Fonseca, Ilda Simões, Silvia Vilares Conde, Miguel Castelo-Branco, Raquel Seiça
Microvascular dysfunction has been suggested to trigger adipose tissue dysfunction in obesity. This study investigates the hypothesis that glycation impairs microvascular architecture and expandability with an impact on insulin signalling. Animal models supplemented with methylglyoxal (MG), maintained with a high-fat diet (HFD) or both (HFDMG) were studied for periepididymal adipose (pEAT) tissue hypoxia and local and systemic insulin resistance. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to quantify blood flow in vivo, showing MG-induced reduction of pEAT blood flow...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28489922/contribution-of-thrombin-reactive-brain-pericytes-to-blood-brain-barrier-dysfunction-in-an-in-vivo-mouse-model-of-obesity-associated-diabetes-and-an-in-vitro-rat-model
#19
Takashi Machida, Fuyuko Takata, Junichi Matsumoto, Tomoyuki Miyamura, Ryosuke Hirata, Ikuya Kimura, Yasufumi Kataoka, Shinya Dohgu, Atsushi Yamauchi
Diabetic complications are characterized by the dysfunction of pericytes located around microvascular endothelial cells. The blood-brain barrier (BBB) exhibits hyperpermeability with progression of diabetes. Therefore, brain pericytes at the BBB may be involved in diabetic complications of the central nervous system (CNS). We hypothesized that brain pericytes respond to increased brain thrombin levels in diabetes, leading to BBB dysfunction and diabetic CNS complications. Mice were fed a high-fat diet (HFD) for 2 or 8 weeks to induce obesity...
2017: PloS One
https://www.readbyqxmd.com/read/28486920/mitochondria-a-novel-therapeutic-target-in-diabetic-nephropathy
#20
Shikun Yang, Yachun Han, Jun Liu, Panai Song, Xiaoxuan Xu, Li Zhao, Chun Hu, Li Xiao, Fuyou Liu, Hao Zhang, Lin Sun
Diabetic nephropathy (DN) is an important diabetic microvascular complication, and it is becoming the leading cause of end-stage renal disease worldwide. Unfortunately, there are no effective therapies to treat established DN. Therefore, new therapeutic targets are urgently required. Accumulating studies indicate that mitochondrial dysfunction is central to the pathogenesis of DN, such as elevated oxidative stress induced by disorders of the mitochondrial respiratory chain complex and mitochondrial dynamic disorders...
May 9, 2017: Current Medicinal Chemistry
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