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Microvascular Dysfunction

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https://www.readbyqxmd.com/read/29149942/mechanisms-of-organ-dysfunction-in-sepsis
#1
REVIEW
Rachel Pool, Hernando Gomez, John A Kellum
Sepsis-associated organ dysfunction involves multiple responses to inflammation, including endothelial and microvascular dysfunction, immune and autonomic dysregulation, and cellular metabolic reprogramming. The effect of targeting these mechanistic pathways on short- and long-term outcomes depends highly on the timing of therapeutic intervention. Furthermore, there is a need to understand the adaptive or maladaptive character of these mechanisms, to discover phase-specific biomarkers to guide therapy, and to conceptualize these mechanisms in terms of resistance and tolerance...
January 2018: Critical Care Clinics
https://www.readbyqxmd.com/read/29146670/three-vessel-assessment-of-coronary-microvascular-dysfunction-in-patients-with-clinical-suspicion-of-ischemia-prospective-observational-study-with-the-index-of-microcirculatory-resistance
#2
Yuhei Kobayashi, Joo Myung Lee, William F Fearon, Jang Hoon Lee, Takeshi Nishi, Dong-Hyun Choi, Frederik M Zimmermann, Ji-Hyun Jung, Hyun-Jung Lee, Joon-Hyung Doh, Chang-Wook Nam, Eun-Seok Shin, Bon-Kwon Koo
BACKGROUND: Difficulty directly visualizing the coronary microvasculature as opposed to the epicardial coronary artery makes its assessment challenging. The goal of this study is to measure the index of microcirculatory resistance (IMR) in all 3 major coronary vessels to identify the clinical and angiographic predictors of an abnormal IMR. METHODS AND RESULTS: Ninety-three patients who underwent coronary physiological assessment in all 3 major coronary vessels were prospectively enrolled (59...
November 2017: Circulation. Cardiovascular Interventions
https://www.readbyqxmd.com/read/29141949/microvascular-insulin-resistance-in-skeletal-muscle-and-brain-occurs-early-in-the-development-of-juvenile-obesity-in-pigs
#3
T Dylan Olver, Zachary Ian Grunewald, Thomas J Jurrissen, Rebecca Ek MacPherson, Paul J LeBlanc, Teagan R Schnurbusch, Alana M Czajkowski, Maurice Harold Laughlin, R Scott Rector, Shawn B Bender, Eric M Walters, Craig A Emter, Jaume Padilla
BACKGROUND: Impaired microvascular insulin signaling may develop prior to overt indices of microvascular endothelial dysfunction and represent an early pathological feature of adolescent obesity. Using a translational porcine model of juvenile obesity, we tested the hypotheses that in the early stages of obesity development, impaired insulin signaling manifests in skeletal muscle (triceps), brain (prefrontal cortex) and corresponding vasculatures, and that depressed insulin-induced vasodilation is reversible with acute inhibition of protein kinase C beta (PKCβ)...
November 15, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29141862/the-activation-of-human-dermal-microvascular-cells-by-poly-i-c-lipopolysaccharide-imiquimod-and-odn2395-is-mediated-by-the-fli1-foxo3a-pathway
#4
Lukasz Stawski, Grace Marden, Maria Trojanowska
Endothelial cell (EC) dysfunction has been associated with inflammatory and autoimmune diseases; however, the factors contributing to this dysfunction have not been fully explored. Because activation of TLRs has been implicated in autoimmune diseases, the goal of this study was to determine the effects of TLR ligands on EC function. Human dermal microvascular ECs (HDMECs) treated with TLR3 [Poly(I:C)], TLR4 (LPS), and TLR7 (imiquimod) agonists showed decreased proliferation and a reduced total number of branching tubules in three-dimensional human dermal organoid ex vivo culture...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29136088/abcd1-dysfunction-alters-white-matter-microvascular-perfusion
#5
Arne Lauer, Xiao Da, Mikkel Bo Hansen, Gregoire Boulouis, Yangming Ou, Xuezhu Cai, Afonso Liberato Celso Pedrotti, Jayashree Kalpathy-Cramer, Paul Caruso, Douglas L Hayden, Natalia Rost, Kim Mouridsen, Florian S Eichler, Bruce Rosen, Patricia L Musolino
Cerebral X-linked adrenoleukodystrophy is a devastating neurodegenerative disorder caused by mutations in the ABCD1 gene, which lead to a rapidly progressive cerebral inflammatory demyelination in up to 60% of affected males. Selective brain endothelial dysfunction and increased permeability of the blood-brain barrier suggest that white matter microvascular dysfunction contributes to the conversion to cerebral disease. Applying a vascular model to conventional dynamic susceptibility contrast magnetic resonance perfusion imaging, we demonstrate that lack of ABCD1 function causes increased capillary flow heterogeneity in asymptomatic hemizygotes predominantly in the white matter regions and developmental stages with the highest probability for conversion to cerebral disease...
November 9, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29135346/cerebral-artery-myogenic-reactivity-the-next-frontier-in-developing-effective-interventions-for-subarachnoid-hemorrhage
#6
Darcy Lidington, Jeffrey T Kroetsch, Steffen-Sebastian Bolz
Aneurysmal subarachnoid hemorrhage (SAH) is a devastating cerebral event that kills or debilitates the majority of those afflicted. The blood that spills into the subarachnoid space stimulates profound cerebral artery vasoconstriction and consequently, cerebral ischemia. Thus, once the initial bleeding in SAH is appropriately managed, the clinical focus shifts to maintaining/improving cerebral perfusion. However, current therapeutic interventions largely fail to improve clinical outcome, because they do not effectively restore normal cerebral artery function...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29133357/myeloid-derived-suppressor-cells-ameliorate-cyclosporine-a-induced-hypertension-in-mice
#7
Valorie L Chiasson, Kelsey R Bounds, Piyali Chatterjee, Lochana Manandhar, Abhinandan R Pakanati, Marcos Hernandez, Bilal Aziz, Brett M Mitchell
The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice...
November 13, 2017: Hypertension
https://www.readbyqxmd.com/read/29132649/doppler-versus-thermodilution-derived-coronary-microvascular-resistance-to-predict-coronary-microvascular-dysfunction-in-patients-with-acute-myocardial-infarction-or-stable-angina-pectoris
#8
Rupert P Williams, Guus A de Waard, Kalpa De Silva, Matthew Lumley, Kaleab Asrress, Satpal Arri, Howard Ellis, Awais Mir, Brian Clapp, Amedeo Chiribiri, Sven Plein, Paul F Teunissen, Maurits R Hollander, Michael Marber, Simon Redwood, Niels van Royen, Divaka Perera
Coronary microvascular resistance is increasingly measured as a predictor of clinical outcomes, but there is no accepted gold-standard measurement. We compared the diagnostic accuracy of 2 invasive indices of microvascular resistance, Doppler-derived hyperemic microvascular resistance (hMR) and thermodilution-derived index of microcirculatory resistance (IMR), at predicting microvascular dysfunction. A total of 54 patients (61 ± 10 years) who underwent cardiac catheterization for stable coronary artery disease (n = 10) or acute myocardial infarction (n = 44) had simultaneous intracoronary pressure, Doppler flow velocity and thermodilution flow data acquired from 74 unobstructed vessels, at rest and during hyperemia...
October 10, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/29130567/treatment-strategies-in-coronary-microvascular-dysfunction-a-systematic-review-of-interventional-studies
#9
Hannah E Suhrs, Marie M Michelsen, Eva Prescott
Coronary microvascular dysfunction has been associated with a wide spectrum of diseases and conditions, and it has proven to be a strong prognostic marker of morbidity and mortality. Despite increased attention guideline-based treatment recommendations are lacking. We performed a systematic review of pharmacological and non-pharmacological interventions to improve coronary perfusion, assessed by intracoronary Doppler, transthoracic Doppler echocardiography, positron emission tomography, cardiac magnetic resonance imaging, transthoracic contrast perfusion echocardiography and dilution techniques...
November 11, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/29128906/toll-like-receptor-3-mediates-hiv-1-induced-interleukin-6-expression-in-the-human-brain-endothelium-via-tak1-and-jnk-pathways-implications-for-viral-neuropathogenesis
#10
Biju Bhargavan, Georgette D Kanmogne
HIV-1-associated neurocognitive disorders (HAND) is associated with blood-brain-barrier (BBB) inflammation, and inflammation involves toll-like receptors (TLRs) signaling. It is not known whether primary human brain microvascular endothelial cells (HBMEC), the major BBB component, express TLRs or whether TLRs are involved in BBB dysfunction and HAND. We demonstrate that HBMEC express TLR3, 4, 5, 7, 9, and 10, and TLR3 was the most abundant. HIV-1 and TLR3 activation increased endothelial TLR3 transcription and expression...
November 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29128796/nanomechanical-testing-of-drug-activities-at-the-cellular-level-case-study-for-endothelium-targeted-drugs
#11
Agnieszka M Kolodziejczyk, Marta Targosz-Korecka, Marek Szymonski
BACKGROUND: The pharmacological treatment of cardiovascular diseases that may potentially be attributed to endothelial dysfunction often requires the application of endothelium-targeted drugs. Simvastatin is one of such drugs currently on the market due to its established anti-inflammatory activities. The nanomechanical response to drug treatment at the cellular level is not yet known. However, this response mechanism is promising as a prospective testing method for newly developing drugs...
June 24, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29128669/wip1-regulates-blood-brain-barrier-function-and-neuro-inflammation-induced-by-lipopolysaccharide-via-the-sonic-hedgehog-signaling-signaling-pathway
#12
Hong Zhen, Lize Zhao, Zhangjun Ling, Li Kuo, Xiarui Xue, Jiaxiu Feng
The blood brain barrier (BBB) is a diffusion barrier that maintains the brain environment. Wip1 is a nuclear phosphatase induced by many factors and involved in various stresses, tumorigenesis, organismal aging, and neurogenesis. Wip1's role in BBB integrity has not been thoroughly investigated. The purpose of the present study was to investigate the effect and mechanism of Wip1 on lipopolysaccharide (LPS)-induced BBB dysfunction and inflammation in an in vitro BBB model. The in vitro BBB model was established by co-culturing human brain-microvascular endothelial cells and human astrocytes and then exposing them to 1μg/ml LPS for 6, 12, 18, 24, and 48h...
November 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29128377/viral-hemorrhagic-fever-in-the-tropics-report-from-the-task-force-on-tropical-diseases-by-the-world-federation-of-societies-of-intensive-and-critical-care-medicine
#13
REVIEW
Jorge Luis Hidalgo Marroquin, Guy A Richards, Juan Ignacio Silesky Jiménez, Tim Baker, Pravin Amin
Viral hemorrhagic fevers (VHFs) are a group of illnesses caused by four families of viruses namely Arenaviruses, Filoviruses, Bunyaviruses, and Flaviviruses. Humans are not the natural reservoir for any of these organisms and acquire the disease through vectors from animal reservoirs. In some conditions human to human transmission is possible increasing the risk to healthy individuals in the vicinity, more so to Health Care Workers (HCW). The pathogenesis of VHF, though poorly understood, varies according to the viruses involved...
November 4, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/29128366/vaccarin-protects-human-microvascular-endothelial-cells-from-apoptosis-via-attenuation-of-hdac1-and-oxidative-stress
#14
Xuexue Zhu, Yueyue Lei, Fanggen Tan, Leilei Gong, Haifeng Gong, Wei Yang, Ting Chen, Zhixuan Zhang, Weiwei Cai, Bao Hou, Xu Wang, Haijian Sun, Yuetao Zhou, Liying Qiu
Vaccarin (VAC), an active flavonoid glycoside from vaccariae semen, exhibits extensive biological activities including vascular endothelial cell protective effects. Histone deacetylase1 (HDAC1) is an epigenetic regulator in cellular apoptosis. In this study, we evaluated the protective effects of VAC on high glucose (HG)-induced cell apoptosis in human microvascular endothelial cells (HMEC-1). The levels of reactive oxygen species, activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were measured...
November 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29126250/diabetic-microvascular-disease-an-endocrine-society-scientific-statement
#15
Eugene J Barrett, Zhenqi Liu, Mogher Khamaisi, George L King, Ronald Klein, Barbara E K Klein, Timothy M Hughes, Suzanne Craft, Barry I Freedman, Donald W Bowden, Aaron I Vinik, Carolina M Casellini
Both type 1 and type 2 diabetes adversely affect the microvasculature in multiple organs. Our understanding of the genesis of this injury and of potential interventions to prevent, limit, or reverse injury/dysfunction is continuously evolving. This statement reviews biochemical/cellular pathways involved in facilitating and abrogating microvascular injury. The statement summarizes the types of injury/dysfunction that occur in the three classical diabetes microvascular target tissues, the eye, the kidney, and the peripheral nervous system; the statement also reviews information on the effects of diabetes and insulin resistance on the microvasculature of skin, brain, adipose tissue, and cardiac and skeletal muscle...
November 8, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29122956/characterization-of-age-related-penile-microvascular-hemodynamic-impairment-using-laser-speckle-contrast-imaging-possible-role-of-increased-fibrogenesis
#16
Seung-Ryeol Lee, Ki-Ho Kim, Ho-Song You, Johnny Fu, Tung-Chin Mike Hsieh, Valmik Bhargava, M Raj Rajasekaran
Current technology for penile hemodynamic evaluations in small animals is invasive and has limitations. We evaluated a novel laser speckle contrast imaging (LSCI) technique to determine age-related changes in penile microvascular perfusion (PMP) and tested the role of cavernosal muscle (CC) fibrosis mediated by Wnt-TGF β1 signaling pathways in a mouse model. Ten young (2-3 months) and old (24-28 months) wild-type C57BL6 male mice were subjected to PMP measured using a LSCI system. Penile blood flow (PBF, peak systolic velocity, PSV) was also measured using a color Doppler ultrasound for comparison...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29121742/retinopathy-and-left-ventricular-hypertrophy-in-patients-with-chronic-kidney-disease-interrelationship-and-impact-on-clinical-outcomes
#17
Yaeni Kim, Jung Sun Cho, Won-Kyung Cho, Hye Eun Yoon, Yu Ah Hong, Yoon Kyung Chang, Chul Woo Yang, Suk Young Kim, Hyeon Seok Hwang
BACKGROUND: Retinopathy and left ventricular hypertrophy (LVH) are representative markers of microvascular and cardiac dysfunction in patients with chronic kidney disease (CKD). However, their relationship and their combined effects on clinical outcomes are unknown. METHODS: We included 401 patients with nondialysis-dependent CKD stage 3-5 who had been examined with fundus photography for diabetic or hypertensive retinopathy. The presence of LVH was identified by echocardiography...
December 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/29121455/bench-to-bedside-and-back-again-finding-the-goldilocks-zone-within-the-scleroderma-universe
#18
EDITORIAL
Janet E Pope, Jason J Lee, Christopher P Denton
Systemic sclerosis (SSc) is a complex inflammatory connective tissue disease characterized by skin thickening, organ fibrosis and vasculopathy [1, 2]. The underlying disease mechanisms and pathophysiology are not fully understood. However, it appears to be, at least in part, driven by autoimmunity and inflammation associated with microvascular dysfunction ultimately resulting in excess extracellular matrix deposition in target organs [2-4]. Clinical heterogeneity coupled with our lack of understanding of the disease pathogenesis means that current treatment strategies are mostly organ based therapies using anti-rheumatic drugs that were originally approved for other indications [5]...
November 9, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29121074/proteome-profiling-in-the-aorta-and-kidney-of-type-1-diabetic-rats
#19
Moustafa Al Hariri, Mohamad Elmedawar, Rui Zhu, Miran A Jaffa, Jingfu Zhao, Parvin Mirzaei, Adnan Ahmed, Firas Kobeissy, Fuad N Ziyadeh, Yehia Mechref, Ayad A Jaffa
Diabetes is associated with a number of metabolic and cardiovascular risk factors that contribute to a high rate of microvascular and macrovascular complications. The risk factors and mechanisms that contribute to the development of micro- and macrovascular disease in diabetes are not fully explained. In this study, we employed mass spectrometric analysis using tandem LC-MS/MS to generate a proteomic profile of protein abundance and post-translational modifications (PTM) in the aorta and kidney of diabetic rats...
2017: PloS One
https://www.readbyqxmd.com/read/29119919/polyphenols-and-microvascular-function-in-humans-a-systematic-review
#20
Kirsty A Woodward, Richard Draijer, Dick H J Thijssen, David A Low
BACKGROUND: Polyphenol-rich dietary sources are acknowledged to have potential cardiovascular health benefits, particularly in reducing cardiovascular disease risk. METHODS: This systematic review sought to determine the effect of polyphenol-rich foods and beverages upon microvascular function, which is of considerable importance in its contribution towards the pathophysiology of microvascular-related complications but also in the future development of (macro-vessel) cardiovascular disease...
November 8, 2017: Current Pharmaceutical Design
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