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vascular remodeling and hypertension

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https://www.readbyqxmd.com/read/30325476/-riskstratification-in-pulmonary-arterial-hypertension-renders-better-treatment-and-prognosis-at-highly-specialised-centers
#1
Göran Rådegran
Pulmonary arterial hypertension (PAH) is a progressive vascular disease, due to vasoconstriction and remodelling of pulmonary arteries. Survival has from diagnosis, if untreated, been found to be 1 to 2.8 years, depending on whether related to rheumatic disease or not. The ESC/ERS risk stratification tool provides a new approach to evaluate the clinical status of PAH patients. It supports a refined treatment strategy, based on risk assessment at diagnosis and early follow-up, with the aim to identify patients early and initiate, as well as adjust treatment individually, striving for the patients to remain in, or improve to low risk status, whereby survival is markedly improved...
October 15, 2018: Läkartidningen
https://www.readbyqxmd.com/read/30325182/androgens-in-maternal-vascular-and-placental-function-implications-for-preeclampsia-pathogenesis
#2
Sathish Kumar, Geoffrey H Gordon, David H Abbott, Jay S Mishra
Adequate maternal vascular adaptations and blood supply to the uterus and placenta are crucial for optimal oxygen and nutrient transport to growing fetuses of eutherian mammals, including humans. Multiple factors contribute to hemodynamics and structuring of placental vasculature essential for term pregnancy with minimal complications. In women, failure to achieve or sustain favorable pregnancy progression is, not surprisingly, associated with high incidence of antenatal complications, including preeclampsia, a hypertensive disorder of pregnancy...
October 16, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/30321538/high-salt-induced-hypertrophy-of-human-vascular-smooth-muscle-cells-associated-with-a-decrease-in-glycocalyx
#3
Ghassan Bkaily, Yanick Simon, Istok Menkovic, Carl Bkaily, Danielle Jacques
All health organizations agree that, presently, the average daily salt (sodium chloride) consumption per person has attained almost double the recommended amount. A chronic high salt diet contributes to the increase in blood pressure and to the development of cardiovascular disease. Although our knowledge of hypertension, in general, is abundant, little is known about salt-sensitive hypertension. Here we tested the hypothesis that acute and/or chronic high salt mimicking that present in high-salt sensitive hypertensive patients may induce hypertrophy of human vascular smooth muscle cells (hVSMCs) and their nuclei that are associated with damage to the plasma membrane glycocalyx...
October 12, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/30315607/right-atrial-to-left-atrial-volume-index-ratio-is-associated-with-increased-mortality-in-patients-with-pulmonary-hypertension
#4
Manu M Mysore, Kenneth C Bilchick, Priscilla Ababio, Benjamin K Ruth, William C Harding, Khadijah Breathett, Kimberley Chadwell, Brandy Patterson, Hunter Mwansa, Christiana M Jeukeng, Younghoon Kwon, Jamie L W Kennedy, Andrew D Mihalek, Sula Mazimba
BACKGROUND: Pulmonary hypertension (PH) is characterized by increased pulmonary vascular resistance leading to right heart failure. Elevated right atrial (RA) pressure reflects right ventricular (RV) pressure overload and is an established risk factor for mortality in PH. We hypothesized that PH patients with an increased ratio of RA to LA volume index (RAVI/LAVI), would have increased mortality. METHODS: We evaluated the association of RAVI/LAVI with mortality in 124 patients seen at a single academic center's PH clinic after adjusting for the REVEAL risk score, an established risk score in PH...
October 12, 2018: Echocardiography
https://www.readbyqxmd.com/read/30315540/mechanobiology-and-vascular-remodeling-from-membrane-to-nucleus
#5
Ying-Xin Qi, Yue Han, Zong-Lai Jiang
Vascular endothelial cells (ECs) and smooth muscle cells (VSMCs) are constantly exposed to hemodynamic forces in vivo, including flow shear stress and cyclic stretch caused by the blood flow. Numerous researches revealed that during various cardiovascular diseases such as atherosclerosis, hypertension, and vein graft, abnormal (pathological) mechanical forces play crucial roles in the dysfunction of ECs and VSMCs, which is the fundamental process during both vascular homeostasis and remodeling. Hemodynamic forces trigger several membrane molecules and structures, such as integrin, ion channel, primary cilia, etc...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/30312106/bone-morphogenetic-protein-9-is-a-mechanistic-biomarker-of-portopulmonary-hypertension
#6
Ivana Nikolic, Lai-Ming Yung, Peiran Yang, Rajeev Malhotra, Samuel D Paskin-Flerlage, Teresa Dinter, Geoffrey A Bocobo, Kathleen E Tumelty, Anthony J Faugno, Luca Troncone, Megan E McNeil, Xiuli Huang, Kathryn R Coser, Carol S C Lai, Paul D Upton, Marie Jose Goumans, Roham T Zamanian, C Gregory Elliott, Arthur Lee, Wei Zheng, Stephen P Berasi, Christine Huard, Nicholas W Morrell, Raymond T Chung, Richard W Channick, Kari E Roberts, Paul B Yu
RATIONALE: Bone Morphogenetic Protein 9 (BMP9) is a circulating endothelial quiescence factor with protective effects in pulmonary arterial hypertension (PAH). Loss-of-function mutations in BMP9, its receptors and downstream effectors have been reported in heritable PAH. OBJECTIVES: We sought to determine how an acquired deficiency of BMP9 signaling might contribute to PAH. METHODS AND RESULTS: Plasma levels of BMP9 and antagonist soluble Endoglin (sEng) were measured in Group 1 PAH, Group 2 and 3 pulmonary hypertension (PH), and in patients with severe liver disease without PAH...
October 12, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/30305109/upregulation-of-microrna-17-5p-contributes-to-hypoxia-induced-proliferation-in-human-pulmonary-artery-smooth-muscle-cells-through-modulation-of-p21-and-pten
#7
Guangjie Liu, Peng Hao, Jie Xu, Liming Wang, Yuchuan Wang, Ruifang Han, Ming Ying, Shuangshuang Sui, Jinghua Liu, Xuan Li
BACKGROUND: Pulmonary arterial smooth muscle cell (PASMC) proliferation in response to hypoxia plays an important role in the vascular remodelling that occurs in hypoxic pulmonary hypertension. MicroRNAs (miRs) are emerging as important regulators in the progression of pulmonary hypertension. In this study, we investigated whether the expression of miR-17-5p is modulated by hypoxia and is involved in the hypoxia-induced proliferation of PASMCs. METHODS: Human PASMCs were cultured under hypoxic conditions...
October 10, 2018: Respiratory Research
https://www.readbyqxmd.com/read/30298006/luteolin-inhibits-vascular-smooth-muscle-cell-proliferation-and-migration-by-inhibiting-tgfbr1-signaling
#8
Yu-Ting Wu, Ling Chen, Zhang-Bin Tan, Hui-Jie Fan, Ling-Peng Xie, Wen-Tong Zhang, Hong-Mei Chen, Jun Li, Bin Liu, Ying-Chun Zhou
Vascular smooth muscle cell (VSMC) proliferation and migration play a critical role in the development of arterial remodeling during various vascular diseases including atherosclerosis, hypertension, and related diseases. Luteolin is a food-derived flavonoid that exerts protective effects on cardiovascular diseases. Here, we investigated whether transforming growth factor-β receptor 1 (TGFBR1) signaling underlies the inhibitory effects of luteolin on VSMC proliferation and migration. We found that luteolin reduced the proliferation and migration of VSMCs, specifically A7r5 and HASMC cells, in a dose-dependent manner, based on MTS and EdU, and Transwell and wound healing assays, respectively...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/30298002/maprotiline-prevents-monocrotaline-induced-pulmonary-arterial-hypertension-in-rats
#9
Yi Tong, Qian Jiao, Yuanru Liu, Jiankun Lv, Rui Wang, Lili Zhu
Pulmonary arterial hypertension (PAH) is a progressive disease caused by increased pulmonary artery pressure and pulmonary vascular resistance, eventually leading to right heart failure until death. Soluble guanylate cyclase (sGC) has been regarded as an attractive drug target in treating PAH. In this study, we discovered that maprotiline, a tetracyclic antidepressant, bound to the full-length recombinant sGC with a high affinity ( K D = 0.307 μM). Further study demonstrated that maprotiline concentration-dependently inhibited the proliferation of hypoxia-induced human pulmonary artery smooth muscle cells...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/30291516/obesity-and-pulmonary-hypertension
#10
REVIEW
Karnika Ayinapudi, Twinkle Singh, Ayush Motwani, Thierry H Le Jemtel, Suzanne Oparil
PURPOSE OF REVIEW: Whether the present obesity epidemic will increase the prevalence of pulmonary hypertension over the next decades is unclear. We review the obesity-related mechanisms that may further the development and progression of pulmonary hypertension. RECENT FINDINGS: Systemic and local inflammation, insulin resistance and oxidative stress contribute to the pathobiology of obesity and pulmonary arterial hypertension. Preliminary data suggest that expansion of adipose tissue surrounding the pulmonary artery may hasten the progression of pulmonary arterial hypertension in obese persons...
October 5, 2018: Current Hypertension Reports
https://www.readbyqxmd.com/read/30291325/the-cofilin-phosphatase-slingshot-homolog-1-restrains-angiotensin-ii-induced-vascular-hypertrophy-and-fibrosis-in-vivo
#11
Holly C Williams, Jing Ma, Daiana Weiss, Bernard Lassègue, Roy L Sutliff, Alejandra San Martín
The dual specificity phosphatase slingshot homolog 1 (SSH1) contributes to actin remodeling by dephosphorylating and activating the actin-severing protein cofilin. The reorganization of the actin cytoskeleton has been implicated in chronic hypertension and the subsequent mechano-adaptive rearrangement of vessel wall components. Therefore, using a novel Ssh1-/- mouse model, we investigated the potential role of SSH1 in angiotensin II (Ang II)-induced hypertension, and vascular remodeling. We found that loss of SSH1 did not produce overt phenotypic changes and that baseline blood pressures as well as heart rates were comparable between Ssh1+/+ and Ssh1-/- mice...
October 5, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/30284059/hemodynamic-assessment-of-pulmonary-hypertension-in-mice-a-model-based-analysis-of-the-disease-mechanism
#12
M Umar Qureshi, Mitchel J Colebank, L Mihaela Paun, Laura Ellwein Fix, Naomi Chesler, Mansoor A Haider, Nicholas A Hill, Dirk Husmeier, Mette S Olufsen
This study uses a one-dimensional fluid dynamics arterial network model to infer changes in hemodynamic quantities associated with pulmonary hypertension in mice. Data for this study include blood flow and pressure measurements from the main pulmonary artery for 7 control mice with normal pulmonary function and 5 mice with hypoxia-induced pulmonary hypertension. Arterial dimensions for a 21-vessel network are extracted from micro-CT images of lungs from a representative control and hypertensive mouse. Each vessel is represented by its length and radius...
October 3, 2018: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/30282973/exosomal-15-lo2-mediates-hypoxia-induced-pulmonary-artery-hypertension-in-vivo-and-in-vitro
#13
Min Zhang, Wei Xin, Cui Ma, Hongyue Zhang, Min Mao, Ying Liu, Xiaodong Zheng, Lixin Zhang, Xiufeng Yu, Huajian Li, Daling Zhu
Our previous studies have shown that 15-LO2/15-HETE induced by hypoxia played an important role in pulmonary arterial hypertension (PH). However, the transportations of 15-LO2/15-HETE among the cells remain elusive. In this study, we investigated the specific involvement of 15-LO2-containing exosomes in the overproliferation of pulmonary artery endothelial cells (PAECs) induced by hypoxia and the underlying mechanism. In vitro, 15-LO2 was abundantly expressed and enriched in exosomes secreted from hypoxic PAECs, which subsequently activated the STAT3 signaling pathway, resulting in a robust increase in PAECs proliferation...
October 3, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/30280796/the-mechanisms-of-ang-ii-induced-hypertensive-vascular-remodeling-under-suppression-of-cd68-in-macrophages
#14
Z-G Zhao, H-F Wang, Y-W Wang, J Li, Y-X Li, H Xin, J-J Liu, X-M Guan
OBJECTIVE: High blood pressure (hypertension) is one of the most common cardiovascular diseases. In recent years, there were more and more studies on the function of inflammation in hypertension. CD68 mainly mediates the activation of cytokine interleukin-17 (IL-17) signaling pathway and participates in inflammatory responses. It has been studied the function of CD68 and IL-17 in hypertension, but it has not been reported whether it affected hypertension and vascular remodeling when macrophage CD68 expression inhibited...
September 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/30279269/nf-%C3%AE%C2%BAb-responsive-mirna-31-5p-elicits-endothelial-dysfunction-associated-with-preeclampsia-via-downregulation-of-endothelial-nitric-oxide-synthase
#15
Suji Kim, Kyu-Sun Lee, Seunghwan Choi, Joohwan Kim, Dong-Keon Lee, Minsik Park, Wonjin Park, Tae-Hoon Kim, Jong Yun Hwang, Moo-Ho Won, Hansoo Lee, Sungwoo Ryoo, Kwon-Soo Ha, Young-Guen Kwon, Young-Myeong Kim
Inflammatory cytokines, including TNF-α, were elevated in patients with cardiovascular diseases and are also considered as crucial factors in the pathogenesis of preeclampsia; however, the underlying pathogenic mechanism has not been clearly elucidated. The present study provides novel evidence that TNF-α leads to endothelial dysfunction associated with hypertension and vascular remodeling in preeclampsia through downregulation of eNOS by NF-κB-dependent biogenesis of microRNA (miR)-31-5p, which targets eNOS mRNA...
October 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30272025/bone-morphogenetic-protein-signaling-is-required-for-rad51-mediated-maintenance-of-genome-integrity-in-vascular-endothelial-cells
#16
Sanna Vattulainen-Collanus, Mark Southwood, Xu Dong Yang, Stephen Moore, Prajakta Ghatpande, Nicholas W Morrell, Giorgio Lagna, Akiko Hata
The integrity of blood vessels is fundamental to vascular homeostasis. Inactivating mutations in the bone morphogenetic protein (BMP) receptor type II (BMPR2) gene cause hereditary vascular disorders, including pulmonary arterial hypertension and hereditary hemorrhagic telangiectasia, suggesting that BMPR2 and its downstream signaling pathway are pivotal to the maintenance of vascular integrity through an unknown molecular mechanism. Here we report that inactivation of BMPR2 in pulmonary vascular endothelial cells results in a deficit of RAD51, an enzyme essential for DNA repair and replication...
2018: Communications biology
https://www.readbyqxmd.com/read/30266526/topotecan-prevents-hypoxia-induced-pulmonary-arterial-hypertension-and-inhibits-hypoxia-inducible-factor-1%C3%AE-and-trpc-channels
#17
Yongliang Jiang, Yumin Zhou, Gongyong Peng, Nian Liu, Heshen Tian, Dan Pan, Lei Liu, Xing Yang, Chao Li, Wen Li, Ling Chen, Pixin Ran, Aiguo Dai
BACKGROUND: This study aimed to investigate the effects of topotecan (TPT) on the hypoxia-induced pulmonary arterial hypertension (PAH) in a rat model, and to explore the underlying mechanism. METHODS: The experiments were carried out in vitro using rat PASMCs and in vivo using a rat model of hypoxia-induced PAH. RESULTS: TPT significantly suppressed the hypoxia-induced upregulation of HIF-1α and TRPC1/4/6 expression both in pulmonary arterial smooth muscle cells (PASMCs) from normal rats and in pulmonary arteries from PAH model rats...
September 25, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/30265151/western-diet-triggers-toll-like-receptor-4-tlr4-signaling-induced-endothelial-dysfunction-in-female-wistar-rats
#18
Benjamin Kramer, Lucas Martins Franca, Youhua Zhang, Antonio Marcus de Andrade Paes, A Martin Gerdes, Maria Alicia Carrillo-Sepulveda
Overconsumption of a diet rich in fat and carbohydrates, called the western diet, is a major contributor to the global epidemic of cardiovascular disease. Despite previously documented cardiovascular protection exhibited in female rats, this safeguard may be lost under certain metabolic stressors. We hypothesized that female Wistar rats challenged by a western diet composed of 21% fat and 50% carbohydrate (34.1% sucrose) for 17-weeks would develop endothelial dysfunction via endothelial Toll like receptor 4 (TLR4) signaling...
September 28, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/30262154/dissecting-molecular-mechanisms-underlying-pulmonary-vascular-smooth-muscle-cell-dedifferentiation-in-pulmonary-hypertension-role-of-mutated-caveolin-1-cav1-f92a-bone-marrow-mesenchymal-stem-cells
#19
Wancheng Yu, Haiying Chen, Hongli Yang, Jie Ding, Peng Xia, Xu Mei, Lei Wang, Shuangfeng Chen, Chengwei Zou, Le-Xin Wang
BACKGROUND: Pulmonary arterial hypertension (PAH) is characterised by remodelling in vascular smooth muscles, and switching from contractile (differentiated) to synthetic (dedifferentiated) phenotype. This study aimed to investigate the effect of a mutated caveolin-1 (Cav1F92A ) gene from bone marrow mesenchymal stem cells (rBMSCs) on phenotypic switching in the smooth muscle cells during PAH. METHODS: Human pulmonary smooth muscle cells (HPASMCs) were treated with monocrotaline (MCT,1μM), and co-cultured with Cav1F92A gene modified rBMSCs (rBMSCs/Cav1F92A )...
September 7, 2018: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/30260284/pulmonary-microvascular-remodeling-in-chronic-thrombo-embolic-pulmonary-hypertension
#20
Kelly Stam, Richard W B van Duin, Andre Uitterdijk, Ilona Krabbendam-Peters, Oana Sorop, A H Jan Danser, Dirk J Duncker, Daphne Merkus
RATIONALE: Pulmonary vascular remodeling in pulmonary arterial hypertension involves perturbations in the nitric oxide (NO) and endothelin-1 (ET-1) pathways. However, the implications of pulmonary vascular remodeling and these pathways remain unclear in chronic thrombo-embolic pulmonary hypertension (CTEPH). OBJECTIVES: To characterize changes in microvascular morphology and function by assessing the function of the ET-1- and NO-pathways in the regulation of vascular tone in a CTEPH swine model...
September 27, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
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