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https://www.readbyqxmd.com/read/28647645/adding-dimension-to-cellular-mechanotransduction-advances-in-biomedical-engineering-of-multiaxial-cell-stretch-systems-and-their-application-to-cardiovascular-biomechanics-and-mechano-signaling
#1
REVIEW
O Friedrich, D Schneidereit, Y A Nikolaev, V Nikolova-Krstevski, S Schürmann, A Wirth-Hücking, A L Merten, D Fatkin, B Martinac
Hollow organs (e.g. heart) experience pressure-induced mechanical wall stress sensed by molecular mechano-biosensors, including mechanosensitive ion channels, to translate into intracellular signaling. For direct mechanistic studies, stretch devices to apply defined extensions to cells adhered to elastomeric membranes have stimulated mechanotransduction research. However, most engineered systems only exploit unilateral cellular stretch. In addition, it is often taken for granted that stretch applied by hardware translates 1:1 to the cell membrane...
June 21, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28639275/statin-regulated-erk5-stimulates-tight-junction-formation-and-reduces-permeability-in-human-cardiac-endothelial-cells
#2
Emma L Wilkinson, James E Sidaway, Michael J Cross
The MEKK3/MEK5/ERK5 signalling axis is required for cardiovascular development in vivo. We analysed the physiological role of ERK5 in cardiac endothelial cells and the consequence of activation of this kinase by the statin class of HMG Co-A reductase inhibitor drugs. We utilised human microvascular endothelial cells (HCMECs) and altered ERK5 expression using siRNA mediated gene silencing or overexpression of constitutively active MEK5 and ERK5 to reveal a role for ERK5 in regulating endothelial tight junction formation and cell permeability...
June 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28617969/conditionally-targeted-deletion-of-psen1-leads-to-diastolic-heart-dysfunction
#3
Xiao-Wei Song, Qing-Ning Yuan, Ying Tang, Mi Cao, Ya-Feng Shen, Zhen-Yu Zeng, Chang-Hai Lei, SongHua Li, Xian-Xian Zhao, Yong-Ji Yang
Recently, PSEN1 has been reported to have mutations in dilated cardiomyopathy pedigrees. However, the function and mechanism of PSEN1 in cardiomyopathy remains unresolved. Here, we established 4 types of genetically modified mice to determine the function of PSEN1 in cardiac development and pathology. PSEN1 null mutation resulted in perinatal death, retardation of heart growth, ventricular dilatation, septum defects, and valvular thickening. PSEN1 knockout in adults led to decreased muscle fibers, widened sarcomere Z lines and reduced lengths of sarcomeres in cardiomyocytes...
June 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28614788/apelin-modulates-pathological-remodeling-of-lymphatic-endothelium-after-myocardial-infarction
#4
Florence Tatin, Edith Renaud-Gabardos, Anne-Claire Godet, Fransky Hantelys, Francoise Pujol, Florent Morfoisse, Denis Calise, Fanny Viars, Philippe Valet, Bernard Masri, Anne-Catherine Prats, Barbara Garmy-Susini
Lymphatic endothelium serves as a barrier to control fluid balance and immune cell trafficking to maintain tissue homeostasis. Long-term alteration of lymphatic vasculature promotes edema and fibrosis, which is an aggravating factor in the onset of cardiovascular diseases such as myocardial infarction. Apelin is a bioactive peptide that plays a central role in angiogenesis and cardiac contractility. Despite an established role of apelin in lymphangiogenesis, little is known about its function in the cardiac lymphatic endothelium...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28614064/ionising-radiation-increases-permeability-of-endothelium-through-adam10-mediated-cleavage-of-ve-cadherin
#5
Sylwia Kabacik, Ken Raj
The association between ionising radiation (IR) exposure and risk of cardiovascular diseases (CVD) is well documented, but the underlying mechanism is still poorly understood. As atherosclerotic plaques are the most common cause of CVD, we investigated the effects of IR on one of the critical parameters for atherosclerotic plaque formation - endothelium permeability to macromolecules.We used endothelial cells from human coronary artery as a model of the endothelial layer. Our results show that exposure of this endothelial layer to IR increased its permeability to macromolecules of various sizes in a dose-dependent manner...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28590826/minimally-invasive-treatment-of-pediatric-extrinsic-ureteropelvic-junction-obstruction-by-crossing-polar-vessels-is-vascular-hitching-a-definitive-solution-report-of-a-multicenter-survey
#6
Salvatore Fabio Chiarenza, Cosimo Bleve, Paolo Caione, Maria Escolino, Simona Gerocarni Nappo, Rosa Perretta, Angela La Manna, Ciro Esposito
BACKGROUND: This article aimed to evaluate the outcome of laparoscopic vascular hitch (VH) as an effective alternative to dismembered pyeloplasty in the treatment of children with extrinsic ureteropelvic junction obstruction (UPJO) by crossing vessels (CVs), by reporting the experience of three Italian centers of Pediatric Surgery. METHODS: From 2006 to 2014, 54 children (18 girls and 36 boys, average age 10.7 years) affected by suspected extrinsic UPJO by CV were treated in three different institutions: 51 patients underwent laparoscopic VH, while 3 patients, in which a coexisting intrinsic etiology of UPJO was doubtful, underwent laparoscopic dismembered pyeloplasty...
June 7, 2017: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
https://www.readbyqxmd.com/read/28588504/tnf%C3%AE-modulates-cardiac-conduction-by-altering-electrical-coupling-between-myocytes
#7
Sharon A George, Patrick J Calhoun, Robert G Gourdie, James W Smyth, Steven Poelzing
Background: Tumor Necrosis Factor α (TNFα) upregulation during acute inflammatory response has been associated with numerous cardiac effects including modulating Connexin43 and vascular permeability. This may in turn alter cardiac gap junctional (GJ) coupling and extracellular volume (ephaptic coupling) respectively. We hypothesized that acute exposure to pathophysiological TNFα levels can modulate conduction velocity (CV) in the heart by altering electrical coupling: GJ and ephaptic. Methods and Results: Hearts were optically mapped to determine CV from control, TNFα and TNFα + high calcium (2...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28558298/facile-endothelium-protection-from-tnf-%C3%AE-inflammatory-insult-with-surface-topography
#8
Georgios Stefopoulos, Costanza Giampietro, Volkmar Falk, Dimos Poulikakos, Aldo Ferrari
Adverse events triggered by the direct contact between blood and synthetic materials constitute a sincere shortcoming of cardiovascular implant technology. A well-connected autologous endothelium, generated through the process of endothelialization, impedes such interaction and endows the implant luminal interface with optimal protection. The endothelialization of artificial substrates is the result of a complex interplay between endothelial cells (ECs), surface topography, and flow-generated wall shear stress (WSS)...
May 26, 2017: Biomaterials
https://www.readbyqxmd.com/read/28555373/blood-brain-barrier-injury-in-diabetes-unrecognized-effects-on-brain-and-cognition
#9
REVIEW
Marina Bogush, Nathan A Heldt, Yuri Persidsky
Diabetes mellitus (DM) is a disorder due to the inability properly to metabolize glucose associated with dysregulation of metabolic pathways of lipids and proteins resulting in structural and functional changes of various organ systems. DM has detrimental effects on the vasculature, resulting in the development of various cardiovascular diseases and stemming from microvascular injury. The blood brain barrier (BBB) is a highly specialized structure protecting the unique microenvironment of the brain. Endothelial cells, connected by junctional complexes and expressing numerous transporters, constitute the main cell type in the BBB...
May 29, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28553164/tbx20-loss-of-function-mutation-responsible-for-familial-tetralogy-of-fallot-or-sporadic-persistent-truncus-arteriosus
#10
Ri-Tai Huang, Juan Wang, Song Xue, Xing-Biao Qiu, Hong-Yu Shi, Ruo-Gu Li, Xin-Kai Qu, Xiao-Xiao Yang, Hua Liu, Ning Li, Yan-Jie Li, Ying-Jia Xu, Yi-Qing Yang
Congenital heart disease (CHD), the most common form of developmental abnormality in humans, remains a leading cause of morbidity and mortality in neonates. Genetic defects have been recognized as the predominant causes of CHD. Nevertheless, CHD is of substantial genetic heterogeneity and the genetic defects underlying CHD in most cases remain unclear. In the current study, the coding regions and splicing junction sites of the TBX20 gene, which encodes a T-box transcription factor key to cardiovascular morphogenesis, were sequenced in 175 unrelated patients with CHD, and a novel heterozygous TBX20 mutation, p...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28551790/connexin-43-and-mitochondria-in-cardiovascular-health-and-disease
#11
Kerstin Boengler, Rainer Schulz
Connexin 43 (Cx43) is the major connexin protein in ventricular cardiomyocytes. Six Cx43 proteins assemble into so-called hemichannels at the sarcolemma and opposing hemichannels form gap junctions, which allow the passage of small molecules and electrical current flow between adjacent cells. Apart from its localization at the plasma membrane, Cx43 is also present in cardiomyocyte mitochondria, where it is important for mitochondrial function in terms of oxygen consumption and potassium fluxes. The expression of gap junctional and mitochondrial Cx43 is altered under several pathophysiological conditions among them are hypertension, hypertrophy, hypercholesterolemia, ischemia/reperfusion injury, post-infarction remodeling, and heart failure...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28550903/hemodynamic-effects-of-the-abdominal-aortic-and-junctional-tourniquet-in-a-hemorrhagic-swine-model
#12
Jason M Rall, James D Ross, Michael S Clemens, Jennifer M Cox, Theresea A Buckley, Jonathan J Morrison
BACKGROUND: Torso hemorrhage constitutes a leading cause of battlefield mortality. The Abdominal Aortic and Junctional Tourniquet (AAJT) uses a pneumatic bladder to compress the aorta reducing pelvic and lower extremity perfusion; however, concern exists over the risk of caval compression exacerbating hypotension after application. METHODS: Male swine (70-90 kg) were randomized into four groups of 10: presence or absence of hemorrhage and AAJT placement. After a 40% hemorrhage, a 15-min period of hypovolemia was observed before the AAJT application...
May 15, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28533325/physiologic-regulation-of-heart-rate-and-blood-pressure-involves-connexin-36-containing-gap-junctions
#13
Varinder K Lall, Gareth Bruce, Larysa Voytenko, Mark Drinkhill, Kerstin Wellershaus, Klaus Willecke, Jim Deuchars, Susan A Deuchars
Chronically elevated sympathetic nervous activity underlies many cardiovascular diseases. Elucidating the mechanisms contributing to sympathetic nervous system output may reveal new avenues of treatment. The contribution of the gap junctional protein connexin 36 (Cx36) to the regulation of sympathetic activity and thus blood pressure and heart rate was determined using a mouse with specific genetic deletion of Cx36. Ablation of the Cx36 protein was confirmed in sympathetic preganglionic neurons of Cx36 knockout (KO) mice...
May 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28510599/selective-inhibition-of-brain-endothelial-rho-kinase-2-provides-optimal-protection-of-an-in-vitro-blood-brain-barrier-from-tissue-type-plasminogen-activator-and-plasmin
#14
Be'eri Niego, Natasha Lee, Pia Larsson, T Michael De Silva, Amanda E-Ling Au, Fiona McCutcheon, Robert L Medcalf
Rho-kinase (ROCK) inhibition, broadly utilised in cardiovascular disease, may protect the blood-brain barrier (BBB) during thrombolysis from rt-PA-induced damage. While the use of nonselective ROCK inhibitors like fasudil together with rt-PA may be hindered by possible hypotensive side-effects and inadequate capacity to block detrimental rt-PA activity in brain endothelial cells (BECs), selective ROCK-2 inhibition may overcome these limitations. Here, we examined ROCK-2 expression in major brain cells and compared the ability of fasudil and KD025, a selective ROCK-2 inhibitor, to attenuate rt-PA-induced BBB impairment in an in vitro human model...
2017: PloS One
https://www.readbyqxmd.com/read/28495795/the-desmoplakin-intermediate-filament-linkage-regulates-cell-mechanics
#15
Joshua A Broussard, Ruiguo Yang, Changjin Huang, S Shiva P Nathamgari, Allison M Beese, Lisa M Godsel, Sherry Lee, Fan Zhou, Nathan J Sniadecki, Kathleen J Green, Horacio D Espinosa
The translation of mechanical forces into biochemical signals plays a central role in guiding normal physiological processes during tissue development and homeostasis. Interfering with this process contributes to cardiovascular disease, cancer progression, and inherited disorders. The actin-based cytoskeleton and its associated adherens junctions are well-established contributors to mechanosensing and transduction machinery; however, the role of the desmosome/intermediate filament network is poorly understood in this context...
May 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28485540/proteinase-activated-receptor-2-modulates-ve-cadherin-expression-to-affect-human-vascular-endothelial-barrier-function
#16
Rui Zhang, Jianjun Ge
Published data indicate that the protease-activated receptor (PAR) 2 is involved in the pathogenesis of some cardiovascular diseases; the underlying mechanism is to be further investigated. Ve-cadherin is a critical molecule in maintaining the endothelial barrier integrity. This study aims to investigate the role of PAR2 activation in compromising the cardiac endothelial barrier function. In this study, human umbilical vein endothelial cells (Huvec cells) were cultured into monolayers using as an in vitro model of barrier function...
May 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28458438/chronic-lithium-intoxication-varying-electrocardiogram-manifestations
#17
Raja Naga Mahesh Maddala, A J Ashwal, M Sudhakar Rao, R Padmakumar
Lithium is a commonly used drug in psychiatric practice. It is used in the treatment of depression and bipolar disorder. It has a narrow therapeutic index with documented adverse effects even near therapeutic levels. It has myriad of manifestations at toxic levels. The cardiovascular effects range from relatively benign ST-T wave changes to fatal arrhythmias. We describe a case of lithium toxicity which presented as a junctional rhythm and later showed a variety of manifestations such as complete heart block, atrial fibrillation, sinus bradycardia, and finally reverted to sinus rhythm at par with serum lithium levels...
January 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/28457700/human-connexin40-mutations-slow-conduction-and-increase-propensity-for-atrial-fibrillation
#18
Ajita Kanthan, Peter Fahmy, Renuka Rao, Jim Pouliopoulos, Ian E Alexander, Stuart P Thomas, Eddy Kizana
BACKGROUND: Patch clamping studies using non-cardiomyocytes revealed that the human connexin40 mutations P88S, G38D, and A96S are associated with reduced gap junction conductances compared to wild type connexin40 (wtCx40). Their effects within myocytes however are unclear. We aimed to characterise P88S, G38D, and A96S after expression in rat hearts and primary cardiomyocyte cultures. METHODS: Adult Sprague-Dawley rat atria were transduced with a lentivector containing a transgene encoding wtCx40, P88S, G38D, A96S, or eGFP (n=6 per transgene)...
March 21, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/28440499/effects-of-tanshinone-iia-on-the-regulation-of-renal-proximal-tubular-fibrosis
#19
Luoyuan Cao, Baoying Huang, Xianguo Fu, Jing Yang, Yinghua Lin, Feng Lin
The development of diabetes mellitus, along with its complications, is a chronic inflammatory response process. Chronic kidney diseases are characterized by renal fibrosis, and fibrosis is an important pathway for end‑stage renal failure. According to previous studies, high glucose (HG) has been demonstrated to be the most important fibrogenesis‑inducing agent. Tanshinone IIA is one of the main components isolated from Danshen (Salvia miltiorrhiza). Although tanshinone IIA has been widely used for the treatment of cardiovascular diseases, the possible role of tanshinone IIA in fibrosis regulation remains to be elucidated and requires investigation...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28439518/diabetes-adult-neurogenesis-and-brain-remodeling-new-insights-from-rodent-and-zebrafish-models
#20
REVIEW
Anne-Claire Dorsemans, David Couret, Anaïs Hoarau, Olivier Meilhac, Christian Lefebvre d'Hellencourt, Nicolas Diotel
The prevalence of diabetes rapidly increased during the last decades in association with important changes in lifestyle. Diabetes and hyperglycemia are well-known for inducing deleterious effects on physiologic processes, increasing for instance cardiovascular diseases, nephropathy, retinopathy and foot ulceration. Interestingly, diabetes also impairs brain morphology and functions such as (1) decreased neurogenesis (proliferation, differentiation and cell survival), (2) decreased brain volumes, (3) increased blood-brain barrier leakage, (4) increased cognitive impairments, as well as (5) increased stroke incidence and worse neurologic outcomes following stroke...
2017: Neurogenesis (Austin, Tex.)
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