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Microvascular disease

Ryan Rosenberry, Susie Chung, Michael D Nelson
Exercise represents a major hemodynamic stress that demands a highly coordinated neurovascular response in order to match oxygen delivery to metabolic demand. Reactive hyperemia (in response to a brief period of tissue ischemia) is an independent predictor of cardiovascular events and provides important insight into vascular health and vasodilatory capacity. Skeletal muscle oxidative capacity is equally important in health and disease, as it determines the energy supply for myocellular processes. Here, we describe a simple, non-invasive approach using near-infrared spectroscopy to assess each of these major clinical endpoints (reactive hyperemia, neurovascular coupling, and muscle oxidative capacity) during a single clinic or laboratory visit...
February 20, 2018: Journal of Visualized Experiments: JoVE
Shiteng Suo, Lan Zhang, Hui Tang, Qihong Ni, Suqin Li, Haimin Mao, Xiangyu Liu, Shengyun He, Jianxun Qu, Qing Lu, Jianrong Xu
BACKGROUND: Noninvasive cardiovascular magnetic resonance (CMR) techniques including arterial spin labeling (ASL), blood oxygenation level-dependent (BOLD), and intravoxel incoherent motion (IVIM), are capable of measuring tissue perfusion-related parameters. We sought to evaluate and compare these three CMR techniques in characterizing skeletal muscle perfusion in lower extremities and to investigate their abilities to diagnose and assess the severity of peripheral arterial disease (PAD)...
March 19, 2018: Journal of Cardiovascular Magnetic Resonance
Mohamad Hafizi Abu Bakar, Nany Hairunisa, Hasniza Zaman Huri
Altered mitochondrial DNA (mtDNA) is the most common denominator to numerous metabolic diseases. The present study sought to investigate the correlation between mtDNA content in lymphocytes and associated clinical risk factors for impaired fasting glucose (IFG). We included 23 healthy control and 42 IFG participants in this cross-sectional study. The measurements of mtDNA content in lymphocytes and pro-inflammatory markers derived from both normal and diseased individuals were quantified. Spearman partial correlation and multivariate statistical analyses were employed to evaluate the association between mtDNA content and other metabolic covariates in IFG...
March 17, 2018: Clinical and Experimental Medicine
Filipa Caeiro Alves, Rute Aguiar, Pedro Pessegueiro, Carlos Pires
Thrombotic microangiopathy (TMA) comprises a process of sequential endothelial damage, microvascular thrombosis, consumptive thrombocytopenia and microangiopathic haemolytic anaemia that can affect several organs, including the kidney. A 36-year-old woman was presented with a petechial rash 3 weeks after an upper respiratory tract infection. Laboratory results showed normocytic normochromic anaemia, thrombocytopenia and evidence of TMA with decreased haptoglobin, elevated serum lactate dehydrogenase and a peripheral blood smear with numerous schistocytes...
March 17, 2018: BMJ Case Reports
Kazuhiro Yamaguchi, Takao Tsuji, Kazutetsu Aoshiba, Hiroyuki Nakamura
In Europe and America, the newly-developed, simultaneous measurement of diffusing capacity for CO (DLCO ) and NO (DLNO ) has replaced the classic DLCO measurement for detecting the pathophysiological abnormalities in the acinar regions. However, simultaneous measurement of DLCO and DLNO is currently not used by Japanese physicians. To encourage the use of DLNO in Japan, the authors reviewed aspects of simultaneously-estimated DLCO and DLNO from previously published manuscripts. The simultaneous DLCO -DLNO technique identifies the alveolocapillary membrane-related diffusing capacity (membrane component, DM ) and the blood volume in pulmonary microcirculation (VC ); VC is the principal factor constituting the blood component of diffusing capacity (DB ,DB =θ·VC where θ is the specific gas conductance for CO or NO in the blood)...
March 2018: Respiratory Investigation
Yijun Pan, Jennifer L Short, Stephanie A Newman, Kwok H C Choy, Durgesh Tiwari, Christopher Yap, Danielle Senyschyn, William A Banks, Joseph A Nicolazzo
Epidemiological evidence suggests that people with bipolar disorder prescribed lithium exhibit a lower risk of Alzheimer's disease (AD) relative to those prescribed other mood-stabilizing medicines. Lithium chloride (LiCl) reduces brain β-amyloid (Aβ) levels, and the brain clearance of Aβ is reduced in AD. Therefore, the purpose of this study was to assess whether the cognitive benefits of LiCl are associated with enhanced brain clearance of exogenously-administered Aβ. The brain clearance of intracerebroventricularly (icv) administered125 I-Aβ42 was assessed in male Swiss outbred mice administered daily oral NaCl or LiCl (300 mg/kg for 21 days)...
March 12, 2018: Brain, Behavior, and Immunity
Basmah Safdar, Gail D'Onofrio, James Dziura, Raymond R Russell, Caitlin Johnson, Albert J Sinusas
AIMS: Coronary microvascular dysfunction (CMD) is common in patients with non-obstructive coronary arteries but has not been described in low-risk symptomatic patients. We therefore assessed the prevalence and characteristics of CMD in low to moderate risk patients with chest pain in an emergency department. METHODS AND RESULTS: We used three-dimensional Rb82 cardiac positron emission tomography/computed tomography to diagnose coronary artery disease (known or new regional defect, any coronary calcification) and CMD (low coronary flow reserve without coronary artery disease) in chest pain patients after being ruled out for acute myocardial infarction...
March 1, 2018: European Heart Journal. Acute Cardiovascular Care
Yingying Liu, Yudiao Huang, Yueyue Xu, Peng Qu, Minghua Wang
Increased transendothelial permeability and subsequent blood-brain barrier damage play a key role in the pathological progression of human brain ischemia and secondary reperfusion. Memantine is a licensed drug providing clinically relevant efficacy in patients with Alzheimer's disease. However, little information is known regarding its effects on brain endothelial permeability. In this study, we investigated the effects of memantine on endothelial permeability and the underlying mechanisms in an ischemia-reperfusion (I/R) injury model in primary human brain microvascular endothelial cells...
March 15, 2018: IUBMB Life
Julio Rosenstock, Vlado Perkovic, John H Alexander, Mark E Cooper, Nikolaus Marx, Michael J Pencina, Robert D Toto, Christoph Wanner, Bernard Zinman, David Baanstra, Egon Pfarr, Michaela Mattheus, Uli C Broedl, Hans-Juergen Woerle, Jyothis T George, Maximilian von Eynatten, Darren K McGuire
BACKGROUND: Cardiovascular (CV) outcome trials in type 2 diabetes (T2D) have underrepresented patients with chronic kidney disease (CKD), leading to uncertainty regarding their kidney efficacy and safety. The CARMELINA® trial aims to evaluate the effects of linagliptin, a DPP-4 inhibitor, on both CV and kidney outcomes in a study population enriched for cardio-renal risk. METHODS: CARMELINA® is a randomized, double-blind, placebo-controlled clinical trial conducted in 27 countries in T2D patients at high risk of CV and/or kidney events...
March 14, 2018: Cardiovascular Diabetology
Clara Gregori-Pla, Gianluca Cotta, Igor Blanco, Peyman Zirak, Martina Giovannella, Anna Mola, Ana Fortuna, Turgut Durduran, Mercedes Mayos
MOTIVATION: Obstructive sleep apnea (OSA) can impair cerebral vasoreactivity and is associated with an increased risk of cerebrovascular disease. Unfortunately, an easy-to-use, non-invasive, portable monitor of cerebral vasoreactivity does not exist. Therefore, we have evaluated the use of near-infrared diffuse correlation spectroscopy to measure the microvascular cerebral blood flow (CBF) response to a mild head-of-bed position change as a biomarker for the evaluation of cerebral vasoreactivity alteration due to chronic OSA...
2018: PloS One
Daniel Shpilsky, Sebhat Erqou, Sanjay R Patel, Kevin E Kip, Oluremi Ajala, Aryan Aiyer, Patrick J Strollo, Steven E Reis, Oladipupo Olafiranye
Studies have reported an association between obstructive sleep apnea (OSA) and cardiovascular disease (CVD) morbidity and mortality. Proposed mechanisms include endothelial dysfunction and atherosclerosis. We aimed to investigate the associations of OSA with endothelial dysfunction and subclinical atherosclerotic coronary artery disease (CAD), and assess the impact of race on these associations. We used data from the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study, a community-based prospective cohort with approximately equal representation of black and white participants...
March 1, 2018: Vascular Medicine
Erika Gucciardo, Sirpa Loukovaara, Ani Korhonen, Pauliina Repo, Beatriz Martins, Helena Vihinen, Eija Jokitalo, Kaisa Lehti
Proliferative diabetic retinopathy (PDR) is a major diabetic microvascular complication characterized by pathological angiogenesis. Several retinopathy animal models have been developed to study the disease mechanisms and putative targets. However, knowledge on the human proliferative disease remains incomplete, relying on steady-state results from thin histological neovascular tissue sections and vitreous samples. New translational models are thus required to comprehensively understand the disease pathophysiology and develop improved therapeutic interventions...
March 13, 2018: Journal of Pathology
Paolo Severino, Andrea D'Amato, Lucrezia Netti, Mariateresa Pucci, Marialaura De Marchis, Raffaele Palmirotta, Maurizio Volterrani, Massimo Mancone, Francesco Fedele
Diabetes mellitus is one the strongest risk factors for cardiovascular disease and, in particular, for ischemic heart disease (IHD). The pathophysiology of myocardial ischemia in diabetic patients is complex and not fully understood: some diabetic patients have mainly coronary stenosis obstructing blood flow to the myocardium; others present with coronary microvascular disease with an absence of plaques in the epicardial vessels. Ion channels acting in the cross-talk between the myocardial energy state and coronary blood flow may play a role in the pathophysiology of IHD in diabetic patients...
March 10, 2018: International Journal of Molecular Sciences
Hiroya Kuwahara, Jindong Song, Takahiro Shimoura, Kie Yoshida-Tanaka, Tadahaya Mizuno, Tatsuki Mochizuki, Satoshi Zeniya, Fuying Li, Kazutaka Nishina, Tetsuya Nagata, Shingo Ito, Hiroyuki Kusuhara, Takanori Yokota
The blood-brain barrier (BBB) is increasingly regarded as a dynamic interface that adapts to the needs of the brain, responds to physiological changes, and gets affected by and can even promote diseases. Modulation of BBB function at the molecular level in vivo is beneficial for a variety of basic and clinical studies. Here we show that our heteroduplex oligonucleotide (HDO), composed of an antisense oligonucleotide and its complementary RNA, conjugated to α-tocopherol as a delivery ligand, efficiently reduced the expression of organic anion transporter 3 (OAT3) gene in brain microvascular endothelial cells in mice...
March 12, 2018: Scientific Reports
Pooya Mobadersany, Safoora Yousefi, Mohamed Amgad, David A Gutman, Jill S Barnholtz-Sloan, José E Velázquez Vega, Daniel J Brat, Lee A D Cooper
Cancer histology reflects underlying molecular processes and disease progression and contains rich phenotypic information that is predictive of patient outcomes. In this study, we show a computational approach for learning patient outcomes from digital pathology images using deep learning to combine the power of adaptive machine learning algorithms with traditional survival models. We illustrate how these survival convolutional neural networks (SCNNs) can integrate information from both histology images and genomic biomarkers into a single unified framework to predict time-to-event outcomes and show prediction accuracy that surpasses the current clinical paradigm for predicting the overall survival of patients diagnosed with glioma...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ariane L Herrick, Andrea Murray
Most patients with Raynaud's phenomenon (RP) have "benign" primary RP (PRP), but a minority have an underlying cause, for example a connective tissue disease such as systemic sclerosis (SSc). Secondary RP can be associated with structural as well as functional digital vascular changes and can be very severe, potentially progressing to digital ulceration or gangrene. The first step in management is to establish why the patient has RP. This short review discusses the role of nailfold capillaroscopy and thermography in the assessment of RP...
March 8, 2018: Autoimmunity Reviews
Scott K Ferguson, Julie W Harral, David I Pak, Katherine M Redinius, Kurt R Stenmark, Dominik J Schaer, Paul W Buehler, David C Irwin
Free hemoglobin (Hb) associated with hemolysis extravasates into vascular tissue and depletes nitric oxide (NO), which leads to impaired vascular function and could impair skeletal muscle metabolic control during exercise. We tested the hypothesis that: 1) free Hb would extravasate into skeletal muscle tissue, reducing the contracting skeletal muscle O2 delivery/O2 utilization ratio (microvascular PO2 , PO2 mv) to a similar extent as that observed following NO synthase (NOS) blockade, and 2) that the Hb scavenging protein haptoglobin (Hp) would prevent Hb extravasation and inhibit these skeletal muscle tissue effects...
March 8, 2018: Nitric Oxide: Biology and Chemistry
Katrine Laura Rasmussen, Børge Grønne Nordestgaard, Sune Fallgaard Nielsen
BACKGROUND: Whether the complement system is involved in the development of diabetic microvascular disease is unknown. We tested the hypothesis that high concentrations of complement C3 are associated with increased risk of diabetic retinopathy, nephropathy, and neuropathy in individuals from the general population. METHODS: We studied 95202 individuals from the general population with baseline measurements of complement C3, genotyped for rs1065489, rs429608, and rs448260 determining concentrations of complement C3, and enrolled in the Copenhagen General Population Study from 2003 through 2013, following them until April 10, 2013...
March 9, 2018: Clinical Chemistry
Yuka Matsunaga, Masataka Ishimura, Hazumu Nagata, Kiyoshi Uike, Tadamune Kinjo, Masayuki Ochiai, Kenichiro Yamamura, Hidetoshi Takada, Yoshihisa Tanoue, Masaki Hayakawa, Masanori Matsumoto, Toshiro Hara, Shouichi Ohga
BACKGROUND: Thrombotic microangiopathies (TMA) are microvascular occlusive disorders characterized by systemic or intrarenal platelet aggregation, thrombocytopenia, and red cell fragmentation. Post-operative TMA mostly occurs in adult patients with cardiovascular surgery, with the distinct pathophysiology from classical thrombotic thrombocytopenic purpura (TTP) although the exact pathophysiology remains unclear. CASE PRESENTATION: A one-month-old infant developed TMA after the initial surgery of double outlet right ventricle...
February 7, 2018: Pediatrics and Neonatology
Mónica Muñoz-Vega, Felipe Massó, Araceli Páez, Elizabeth Carreón-Torres, Hector A Cabrera-Fuentes, José Manuel Fragoso, Nonanzit Pérez-Hernández, Laurent O Martinez, Souad Najib, Gilberto Vargas-Alarcón, Óscar Pérez-Méndez
BACKGROUND: Primary cultures endothelial cells have been used as models of endothelial related diseases such atherosclerosis. Biological behavior of primary cultures is donor-dependent and data could not be easily reproducible; endothelial cell lines are emerging options, particularly, human dermal microvascular endothelial cells (HMEC-1), that should be validated to substitute primary cultures for the study of HDL functions. METHODS: Morphology, size and granularity of cells were assessed by phase contrast microscopy and flow cytometry of HMEC-1...
March 9, 2018: Lipids in Health and Disease
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