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vascular remodeling and hypertension

Ying Li, Weidong Ren, Xin Wang, Xiaona Yu, Li Cui, Xinyang Li, Xintong Zhang, Bo Shi
Pulmonary hypertension (PH) is a dangerous disease, featured by pulmonary vascular remodeling. Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs) plays crucial roles in this process. MicroRNA-150 (miR-150) level has been found to be reduced in patients with PH, and correlated with the poor survival. This study aimed to investigate the beneficial effect of miR-150 on PH in hypoxia-induced rats, PASMCs and PAECs. The results showed that miR-150 level was reduced in the lung tissue and plasma of hypoxia-treated rats...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yen-Chun Lai, Longfei Wang, Mark T Gladwin
Pulmonary hypertension in the setting of heart failure with preserved ejection fraction (PH-HFpEF) is a growing public health problem that is increasing in prevalence. While PH-HFpEF is defined by a high mean pulmonary artery pressure, high left ventricular end-diastolic pressure and a normal ejection fraction, some HFpEF patients develop PH in the presence of pulmonary vascular remodeling with a high transpulmonary pressure gradient or pulmonary vascular resistance. Aging, increased left atrial pressure and stiffness, mitral regurgitation, as well as features of metabolic syndrome, which include obesity, diabetes, and hypertension, are recognized as risk factors for PH-HFpEF...
December 13, 2018: Journal of Physiology
Marc Humbert, Christophe Guignabert, Sébastien Bonnet, Peter Dorfmüller, James R Klinger, Mark R Nicolls, Andrea J Olschewski, Soni S Pullamsetti, Ralph T Schermuly, Kurt R Stenmark, Marlene Rabinovitch
Clinical and translational research has played a major role in advancing our understanding of pulmonary hypertension (PH), including pulmonary arterial hypertension and other forms of PH with severe vascular remodelling ( e.g. chronic thromboembolic PH and pulmonary veno-occlusive disease). However, PH remains an incurable condition with a high mortality rate, underscoring the need for a better transfer of novel scientific knowledge into healthcare interventions. Herein, we review recent findings in pathology (with the questioning of the strict morphological categorisation of various forms of PH into pre- or post-capillary involvement of pulmonary vessels) and cellular mechanisms contributing to the onset and progression of pulmonary vascular remodelling associated with various forms of PH...
December 13, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Carleene Bryan, Ibrahim Sammour, Kasonya Guerra, Mayank Sharma, Fredrick Dapaah-Siakwan, Jian Huang, Ronald Zambrano, Merline Benny, Shu Wu, Karen Young
BACKGROUND: Inflammation is a key factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Tumor necrosis factor-stimulated protein 6 (TSG-6) is a glycoprotein that modulates inflammation. Here we tested the hypothesis that intra-tracheal (IT) administration of an adenovirus overexpressing TSG-6 (AdTSG-6) would decrease inflammation and restore lung structure in experimental BPD. METHODS: Newborn Sprague-Dawley rats exposed to normoxia (RA) or hyperoxia (85% O2 ) from postnatal day (P) 1-P14 were randomly assigned to receive IT AdTSG-6 or placebo (PL) on P3...
December 11, 2018: Pediatric Research
W-W Qin, Z-L Xin, H-Q Wang, K-P Wang, X-Y Li, X Wang
OBJECTIVE: Lower extremity arteriosclerosis is one of leading causes of death worldwide. Arteriosclerosis is closely related to microvascular endothelial cells. This study was aimed to explore the role of long non-coding RNA ROR in regulations of growth, migration, and angiogenesis of microvascular endothelial cells. MATERIALS AND METHODS: Angiogenesis was determined by the number of tube-like cells on a matrigel extracellular matrix. Cell viability, apoptosis, and migration were determined by CCK-8 assay, PI/FITC-Annexin V staining method, and transwell assay, respectively...
November 2018: European Review for Medical and Pharmacological Sciences
Hiroki Nakamura, Julia Zimmer, Florian Friedmacher, Prem Puri
INTRODUCTION:  Persistent pulmonary hypertension (PPH) is a major cause of morbidity and mortality in newborns with congenital diaphragmatic hernia (CDH). PPH is characterized by increased vascular resistance and smooth muscle cell (SMC) proliferation, leading to obstructive changes in the pulmonary vasculature. Nitric oxide (NO), generated by endothelial NO synthase (eNOS), is an important regulator of vascular tone and plays a key role in pulmonary vasodilatation. NO synthase interacting protein (NOSIP), which is strongly expressed by pulmonary SMCs, has recently been identified to reduce the endogenous NO production by interacting with eNOS...
December 10, 2018: European Journal of Pediatric Surgery
Limor Raz, Yi Yang, Jeffrey Thompson, Sasha Hobson, John Pesko, Shahriar Mobashery, Mayland Chang, Gary Rosenberg
Vascular cognitive impairment dementia (VCID) is a major cause of cognitive loss in the elderly. Matrix metalloproteinases (MMPs) are a family of proteases involved in remodeling the extracellular matrix in development, injury and repair. Blood-brain barrier (BBB) disruption due to inflammation mediated by MMPs is a mechanism of white matter injury. Currently there are no treatments besides the control of vascular risk factors. We tested two MMP-9 inhibitors that improved outcome in acute stroke: DP-460 and SB-3CT...
2018: PloS One
Birger Tielemans, Marion Delcroix, Catharina Belge, Rozenn Quarck
Pulmonary arterial hypertension (PAH) is a severe condition characterised by remodelling of precapillary pulmonary arteries sometimes associated with mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene. Even in the absence of BMPR2 mutations, increased transforming growth factor (TGF)β receptor signalling and decreased BMPRII signalling have been shown to contribute to PAH pathogenesis. In this Keynote, we review the potential mechanisms by which the imbalance of BMP/TGFβ signalling contributes to endothelial dysfunction, vascular remodelling, inflammation and disordered angiogenesis in PAH...
December 7, 2018: Drug Discovery Today
Irma Isordia-Salas, David Santiago-Germán, Megan Carolina Cerda-Mancillas, Jesús Hernández-Juárez, Mariela Bernabé-García, Alfredo Leaños-Miranda, José Antonio Alvarado-Moreno, Abraham Majluf-Cruz
OBJECTIVE: The renin-angiotensin system (RAS) is a hormonal signaling mechanism implicated in the atherosclerosis and regulation of blood pressure. Angiotensin-converting enzyme (ACE) a key enzyme in the RAS, plays important roles in vascular remodeling atherosclerosis, and ischemic stroke. The aim of this study was to examine the possible contribution of the I/D in the ACE gene, M235T and T174M in the angiotensinogen (AGT) gene polymorphisms with ischemic stroke in young Mexican population...
December 3, 2018: Gene
Mao Dai, Rui Xiao, Luyao Cai, Tong Ge, Liping Zhu, Qinghua Hu
Pulmonary hypertension (PH) is a mortal disease featured with pulmonary vascular constriction and remodeling, right heart failure and eventual death. Several reports showed that high mobility group box 1 (HMGB1) appears to be critical for the development of PH, the underlying mechanism, however has not been revealed. Experiments from the current study demonstrated that the HMGB1 level was elevated in the lung tissue and blood plasma of rats after chronic hypoxia exposure and monocrotaline treatment. The HMGB1 was originally located within nucleus and translocated to cytoplasm of pulmonary artery smooth muscle cells (PASMCs) upon hypoxia exposure, a process that appeared mediated by endogenous H2 O2 ...
December 5, 2018: American Journal of Physiology. Cell Physiology
Benjamin Kramer, Lucas Martins França, 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 wk would develop endothelial dysfunction via endothelial Toll-like receptor 4 (TLR4) signaling...
December 1, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Aijun Liu, Yifan Liu, Bin Li, Ming Yang, Yang Liu, Junwu Su
OBJECTIVES: To investigate the functions of miR-223-3p and ITGB3 in pulmonary arterial hypertension (PAH). MATERIALS AND METHODS: Microarray analysis was used to detect differentially expressed genes and microRNAs. In in vitro models, the expressions of miR-223-3p and ITGB3 were detected by qRT-PCR and Western blot. α-SMA expression and cell proliferation were analysed by immunofluorescence and MTT assay, respectively. In in vivo models, PAH progressions were determined by measuring the levels of mPAP and RVSP...
December 3, 2018: Cell Proliferation
Benjamin Strauss, Yassine Sassi, Carlos Bueno-Beti, Zeki Ilkan, Nour Raad, Marine Cacheux, Malik Bisserier, Irene C Turnbull, Erik Kohlbrenner, Roger J Hajjar, Lahouaria Hadri, Fadi G Akar
BACKGROUND: Pulmonary arterial hypertension (PAH) results in right ventricular (RV) failure, electro-mechanical dysfunction and heightened risk of sudden cardiac death (SCD), although exact mechanisms and predisposing factors remain unclear. Because impaired chronotropic response to exercise is a strong predictor of early mortality in patients with PAH, we hypothesized that progressive elevation in heart rate can unmask ventricular tachyarrhythmias (VT) in a rodent model of monocrotaline (MCT)-induced PAH...
November 28, 2018: Journal of Molecular and Cellular Cardiology
Kai Shen, Harshavardhan Kenche, Hua Zhao, Jinping Li, Jasimine Stone
Vinculin is a key player in sensing and responding to external mechanical cues such as extracellular matrix stiffness. Increased matrix stiffness is often associated with certain pathological conditions including hypertension induced cellular cytoskeleton changes in vascular smooth muscle (VSM) cells. However, little is known on how stiffness affects cytoskeletal remodeling via vinculin in VSM cells. Thus, we utilized matrices with elastic moduli that simulate vascular stiffness in different stages of hypertension to investigate how matrix stiffness regulates cell cytoskeleton via vinculin in synthetic VSM cells...
November 27, 2018: Biochemical and Biophysical Research Communications
Carol R Reinero, L Ari Jutkowitz, Nathan Nelson, Isabelle Masseau, Samuel Jennings, Kurt Williams
BACKGROUND: Histologic features of pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) have been described in dogs but without a thorough clinical description. OBJECTIVES: To report the clinical features, diagnostics, treatment, and outcome of dogs with histologic evidence of PVOD and PCH. ANIMALS: Fifteen pet dogs meeting histopathologic criteria of PVOD (occlusive remodeling of small-sized to medium-sized pulmonary veins) or PCH (alveolar capillary proliferation and congestion), or both...
November 29, 2018: Journal of Veterinary Internal Medicine
Li Lu, Xiaodong Sun, Chen Chen, Yating Qin, Xiaomei Guo
Shexiang Baoxin Pill (SBP), derived from the traditional Chinese medicine, has been broadly applied for the treatment of cardiovascular diseases including coronary heart disease, heart failure, and hypertension in East Asia for decades. Emerging pharmacological studies have revealed that SBP displays pleiotropic roles in protecting the cardiovascular system, as seen by the promotion of angiogenesis, amelioration of inflammation, improvement of endothelium dysfunction, mitigation of dyslipidemia, repression of vascular smooth muscle cell proliferation, and migration and restraint of cardiac remodeling...
2018: Frontiers in Pharmacology
Paul-Benoit Poble, Carole Phan, Timothée Quatremare, Jennifer Bordenave, Raphaël Thuillet, Amélie Cumont, Alice Huertas, Ly Tu, Peter Dorfmüller, Marc Humbert, Maria-Rosa Ghigna, Laurent Savale, Christophe Guignabert
Heightened pulmonary artery smooth muscle cell (PA-SMC) proliferation and migration and dynamic remodeling of the extracellular matrix are hallmark pathogenic features of pulmonary arterial hypertension (PAH). Pirfenidone (PFD) is an orally bioavailable pyridone derivative with antifibrotic, antiinflammatory, and antioxidative properties currently used in the treatment of idiopathic pulmonary fibrosis. We therefore evaluated the efficacy of curative treatments with PFD in the sugen/hypoxia (SuHx) rat model of severe pulmonary hypertension...
November 27, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Sachiyo Igata, Nobuhiro Tahara, Yoichi Sugiyama, Munehisa Bekki, Jun Kumanomido, Atsuko Tahara, Akihiro Honda, Shoko Maeda, Kazutaka Nashiki, Tomohisa Nakamura, Jiahui Sun, Toshi Abe, Yoshihiro Fukumoto
Electrocardiogram (ECG) has been widely used for assessment of right ventricular (RV) hypertrophy (RVH) in patients with pulmonary hypertension (PH). However, it still remains unclear which ECG criteria of RVH are useful to predict for the severity of PH. The aim of our study was to examine the utility of ECG findings of RVH in assessment of PH. A total of 53 patients (42 women, mean age; 57.6 ± 16.4 years) with pre-capillary PH, who were diagnosed by right heart catheterization, underwent blood sampling, ECG, and cardiac magnetic resonance within a week before the right heart catheterization...
2018: PloS One
Hung Chang, Cheng-Yi Chang, Hwei-Jen Lee, Ching-Yu Chou, Tz-Chong Chou
BACKGROUND: Magnolol, a major bioactive component extracted from Magnolia officinalis, exerts several beneficial effects, such as anti-inflammatory and anti-hypertensive activities. PURPOSE: In this study, we investigated whether magnolol has a protective effect on pneumonectomy and monocrotaline-induced pulmonary arterial hypertension (PAH) in rats. DESIGN/METHODS: The alterations of right ventricular (RV) hypertrophy, pulmonary vascular remodeling, histopathological parameters, and related gene expression and signaling pathways in lungs by magnolol treatment were studied in the PAH rats...
December 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Li Zhang, Yu-Mei Li, Xi-Xi Zeng, Xiao-Yan Wang, Shao-Kun Chen, Long-Xin Gui, Mo-Jun Lin
BACKGROUND/AIMS: Vascular muscularity is a key event in vessel remodeling during pulmonary artery hypertension (PAH). Endothelial-mesenchymal transdifferentiation (EndMT) has been increasingly reported to play a role in disease occurrence. Galectin-3, a carbohydrate-binding protein regulates cell proliferation, differentiation, migration and neovascularization. However, whether galectin-3 controls endothelial cell transdifferentiation during the development of PAH is unknown. METHODS: Rats were exposed to normoxic or hypoxic conditions (fraction of inspired O2 0...
2018: Cellular Physiology and Biochemistry
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