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Capillary rarefaction

Sun Ah Nam, Wan-Young Kim, Jin-Won Kim, Min Gyu Kang, Sang Hee Park, Myung-Shik Lee, Hyung Wook Kim, Chul Woo Yang, Jin Kim, Yong Kyun Kim
Renal fibrosis is the final common pathway of various renal injuries and it leads to chronic kidney disease. Recent studies reported that FOXD1-lineage pericyte plays a critical role in tubulointerstitial fibrosis (TIF). However the regulatory mechanisms remain unclear. Autophagy is a cellular process of degradation of damaged cytoplasmic components that regulates cell death and proliferation. To investigate the role of autophagy in FOXD1-lineage pericytes on renal TIF, we generated the FOXD1-lineage stromal cell-specific Atg7 deletion (Atg7△FOXD1 ) mice...
December 10, 2018: Biochemical and Biophysical Research Communications
Wen-Ching Shen, Yu-Hsiang Chou, Hsiang-Po Huang, Jenn-Feng Sheen, Shih-Chieh Hung, Hsin-Fu Chen
BACKGROUND: Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI), which is associated with high morbidity and mortality. AKI is a serious and costly medical condition. Effective therapy for AKI is an unmet clinical need, and molecular mechanisms underlying the interactions between an injured kidney and distant organs remain unclear. Therefore, novel therapeutic strategies should be developed. METHODS: We directed the differentiation of human induced pluripotent stem (iPS) cells into endothelial progenitor cells (iEPCs), which were then applied for treating mouse AKI...
December 10, 2018: Stem Cell Research & Therapy
Stefan Peter Mortensen, Kamilla Munch Winding, Ulrik Winning Iepsen, Gregers Winding Munch, Niels Marcussen, Ylva Hellsten, Bente Klarlund Pedersen, Oliver Baum
Type 2 diabetes is associated with microvascular dysfunction, but little is known about how capillary ultrastructure is affected by exercise training. To investigate the effect of two types of exercise training on skeletal muscle capillary ultrastructure and capillarization in individuals with type 2 diabetes, 21 individuals with type 2 diabetes were allocated (randomized controlled trial) to 11 weeks of aerobic exercise training consisting of either moderate-intensity endurance training (END; n=10), or low-volume high-intensity interval training (HIIT; n=11)...
November 27, 2018: Scandinavian Journal of Medicine & Science in Sports
Achim Lother, Lisa Deng, Michael Huck, David Fürst, Jessica Kowalski, Jennifer Susanne Esser, Martin Moser, Christoph Bode, Lutz Hein
Aldosterone is a key factor in adverse cardiovascular remodeling by acting on the mineralocorticoid receptor (MR) in different cell types. Endothelial MR activation mediates hypertrophy, inflammation and fibrosis. Cardiovascular remodeling is often accompanied by impaired angiogenesis, which is a risk factor for the development of heart failure. In this study, we evaluated the impact of MR in endothelial cells on angiogenesis. Deoxycorticosterone acetate (DOCA)-induced hypertension was associated with capillary rarefaction in the heart of wildtype mice but not of mice with cell type-specific MR deletion in endothelial cells...
September 1, 2018: Journal of Endocrinology
Tao Guan, Ke Huang, Yuanyuan Liu, Shihui Hou, Chengfang Hu, Yi Li, Jingbo Zhang, Jinghong Zhao, Jun Zhang, Rupeng Wang, Yunjian Huang
Robo1/Robo2-NCK1/NCK2 signaling pathway controls endothelial cell sprouting and migration induced by Slit2 or VEGF, but whether it is involved in peritubular capillary (PTC) rarefaction of Aristolochic acid nephropathy (AAN) is unclear. In the present study, we evaluated whether AA exerts antiangiogenic effects by targeting this signaling pathways in HUVECs. HUVECs or lentivirus-mediated NCK1-overexpressing HUVECs were stimulated with AA (1, 2 or 3 μg/ml) in the absence or presence of 6 nM Slit2. Our results showed that AAІ (1-3 μg/ml) dose-dependently inhibited the migration and tube formation of HUVECs...
January 2019: Toxicology Letters
Dennis Kannenkeril, Agnes Bosch, Joanna Harazny, Marina Karg, Susanne Jung, Christian Ott, Roland E Schmieder
BACKGROUND: Diabetes converts from a metabolic disorder into a predominantly vascular disease, once its duration extends over several years or/and when additional cardiovascular risk factors such as hypertension coexist. In a cross-sectional analysis we analyzed various vascular parameters in the renal, retinal and systemic circulation, with the goal to identify which vascular parameter of early organ damage is the earliest that can be clinically detected. METHODS: In 111 patients with type 2 diabetes (T2DM) (off any anti-diabetic medication for at least 4 weeks) and 54 subjects without T2DM we compared various parameters of early vascular remodeling in the same patient: urinary albumin creatinine ratio ([UACR], early morning spot urine) and estimated glomerular filtration rate (eGFR), retinal capillary flow (RCF) and intercapillary distance (ICD) as parameters of capillary rarefaction, wall-to-lumen ratio (WLR) of the retinal arterioles [all assessed by Scanning Laser Doppler Flowmetry], and central systolic pressure (cSBP) and central pulse pressure (cPP) [measured by pulse wave analysis, Syphygmocor] both reflecting vascular stiffness of large arteries...
September 19, 2018: Cardiovascular Diabetology
Amaal E Abdulle, Gilles F H Diercks, Martin Feelisch, Douwe J Mulder, Harry van Goor
Systemic sclerosis (SSc) is a rare connective tissue disease characterized by autoimmunity, vasculopathy, and progressive fibrosis typically affecting multiple organs including the skin. SSc often is a lethal disorder, because effective disease-modifying treatment still remains unavailable. Vasculopathy with endothelial dysfunction, perivascular infiltration of mononuclear cells, vascular wall remodeling and rarefaction of capillaries is the hallmark of the disease. Most patients present with vasospastic attacks of the digital arteries referred to as 'Raynaud's phenomenon,' which is often an indication of an underlying widespread vasculopathy...
2018: Frontiers in Physiology
Vanessa Estato, Joice Stipursky, Fabiana Gomes, Tally C Mergener, Edwards Frazão-Teixeira, Silvana Allodi, Eduardo Tibiriçá, Helene S Barbosa, Daniel Adesse
Toxoplasmosis is one of the leading parasitic diseases worldwide. Some data suggest that chronic acquired toxoplasmosis could be linked to behavioral alterations in humans. The parasite infects neurons, forming immunologically silent cysts. Cerebral microcirculation homeostasis is determinant to brain functions, and pathologic states can alter capillarity or blood perfusion, leading to neurodegeneration and cognitive deficits. Albino mice were infected with Toxoplasma gondii (ME49 strain) and analyzed after 10, 40, and 180 days...
November 2018: American Journal of Pathology
Jacqueline Chua, Calvin Woon Loong Chin, Jimmy Hong, Miao Li Chee, Thu-Thao Le, Daniel Shu Wei Ting, Tien Yin Wong, Leopold Schmetterer
OBJECTIVE: Reduction in capillary density or rarefaction is a hallmark of essential hypertension. We measured the retinal capillary density using noninvasive optical coherence tomographic angiography (OCT-A) in adults with treated systemic hypertension and determined possible correlations with ambulatory blood pressure (BP) and renal parameters. METHODS: This observational cross-sectional study consisted of 153 normal eyes from 77 nondiabetic hypertensive adults [mean (SD) age, 58 (9) years; 49% women; 23% poorly controlled BP]...
August 14, 2018: Journal of Hypertension
Alessandro Arrigo, Emanuela Aragona, Luigi Capone, Luisa Pierro, Francesco Romano, Francesco Bandello, Maurizio Battaglia Parodi
PURPOSE: To analyze optical coherence tomography angiography (OCTA) quantitative features in patients affected by new-onset choroidal neovascularization (CNV) in 1 eye and early/intermediate age-related macular degeneration (AMD) in the fellow eye. DESIGN: Case-control study. METHODS: Setting: Clinical practice. STUDY POPULATION: Thirty patients and 30 age-matched controls. OBSERVATION PROCEDURES: Both cohorts underwent complete ophthalmologic examination, including best-corrected visual acuity (BCVA) measurement, biomicroscopy, fluorescein angiography (FA) and indocyanine green angiography (ICGA) examination, optical coherence tomography, and OCTA scans...
November 2018: American Journal of Ophthalmology
Lei Ye, Liping Su, Chenxu Wang, Szejie Loo, Guizhen Tee, Shihua Tan, Sandar Win Khin, Shijie Ko, Boyang Su, Stuart A Cook
Titin (TTN) Truncating variants (TTNtv) in the A-band of TTN predispose the mouse heart to systolic dysfunction when subjected to pressure-loading. However, the effects of TTNtv of the Z-disc are largely unexplored. A rat model of pressure-loaded heart is developed by trans-aortic constriction (TAC). Rats with TTNtv of the Z-disc were randomly assigned to TAC (Z-TAC) or sham-surgery (Z-Sham) and wildtype (WT) littermates served as controls (WT-TAC or WT-Sham). Left ventricular (LV) function was assessed by echocardiography...
2018: PloS One
Yifan Zhang, Daisuke Nakano, Yu Guan, Hirofumi Hitomi, Akiyoshi Uemura, Tsutomu Masaki, Hideki Kobara, Takeshi Sugaya, Akira Nishiyama
Multiple large clinical trials have shown that sodium-glucose cotransporter (SGLT) 2 inhibitors reduce the risk of renal events. However, the mechanism responsible for this outcome remains unknown. Here we investigated the effects of the SGLT2 inhibitor luseogliflozin on the development of renal fibrosis after renal ischemia/reperfusion injury in non-diabetic mice. Luseogliflozin significantly suppressed development of renal fibrosis, prevented peritubular capillary congestion/hemorrhage, attenuated CD31-positive cell loss, suppressed hypoxia, and increased vascular endothelial growth factor (VEGF)-A expression in the kidney after ischemia/reperfusion injury...
September 2018: Kidney International
Diana A Papazova, Merle M Krebber, Nynke R Oosterhuis, Hendrik Gremmels, Arjan D van Zuilen, Jaap A Joles, Marianne C Verhaar
Kidney transplantation (Tx) is considered the only definite treatment for end-stage kidney disease (ESKD) patients. The increasing prevalence of ESKD has necessitated the introduction of transplantation with kidneys from suboptimal donors. There is, however, still a lack of fundamental and longitudinal research on suboptimal kidney transplants. Specifically, there is a demand for accurate pre-Tx predictors of donor kidney function and injury to predict post-Tx outcome. In the present study, we combine rat models of chronic kidney disease (CKD) and renal Tx to dissect the effects of healthy and CKD renal grafts on healthy and CKD recipients...
July 17, 2018: Disease Models & Mechanisms
Gunnar Schley, Jutta Jordan, Stephan Ellmann, Seymour Rosen, Kai-Uwe Eckardt, Michael Uder, Carsten Willam, Tobias Bäuerle
OBJECTIVES: In human chronic kidney disease (CKD) the extent of renal tubulointerstitial fibrosis correlates with progressive loss of renal function. However, fibrosis can so far only be assessed by histology of kidney biopsies. Magnetic resonance imaging (MRI) can provide information about tissue architecture, but its potential to assess fibrosis and inflammation in diseased kidneys remains poorly defined. MATERIALS AND METHODS: We evaluated excised kidneys in a murine adenine-induced nephropathy model for CKD by MRI and correlated quantitative MRI parameters (T1, T2, and T2* relaxation times, apparent diffusion coefficient and fractional anisotropy) with histological hallmarks of progressive CKD, including renal fibrosis, inflammation, and microvascular rarefaction...
2018: PloS One
Baris Afsar, Rengin E Afsar, Tuncay Dagel, Ege Kaya, Suat Erus, Alberto Ortiz, Adrian Covic, Mehmet Kanbay
Capillary rarefaction is broadly defined as a reduction in vascular density. Capillary rarefaction in the kidneys is thought to promote hypoxia, impair hemodynamic responses and predispose to chronic kidney disease (CKD) progression and hypertension development. Various mechanisms have been suggested to play a role in the development of capillary rarefaction, including inflammation, an altered endothelial-tubular epithelial cell crosstalk, a relative deficiency in angiogenic growth factors, loss of pericytes, increased activity of Transforming growth factor -β1 and thrombospondin-1, vitamin D deficiency, a link to lymphatic neoangiogenesis and INK4a/ARF (Cylin-dependent kinase inhibitor 2a; CDKN2A)...
June 2018: Clinical Kidney Journal
Cristian González-Guerrero, José Luis Morgado-Pascual, Pablo Cannata-Ortiz, María Angeles Ramos-Barron, Carlos Gómez-Alamillo, Manuel Arias, Sergio Mezzano, Jesús Egido, Marta Ruiz-Ortega, Alberto Ortiz, Adrián M Ramos
The chemokine CCL20 activates the CCR6 receptor and has been implicated in the pathogenesis of glomerular injury. However, it is unknown whether it contributes to acute kidney injury (AKI). We identified CCL20 as upregulated in a systems biology strategy combining transcriptomics of kidney tissue from experimental toxic folic acid-induced AKI and from stressed cultured tubular cells and have explored the expression and function of CCL20 in experimental and clinical AKI. CCL20 upregulation was confirmed in three models of kidney injury induced by a folic acid overdose, cisplatin or unilateral ureteral obstruction...
July 8, 2018: Journal of Pathology
Megha Agarwal, Nidhi Thareja, Melody Benjamin, Andre Akhondi, George D Mitchell
PURPOSE OF REVIEW: The purpose of this paper is to identify commonly used tyrosine kinase inhibitors (TKIs) that are associated with hypertension, primarily, vascular endothelial growth factor (VEGF) signaling pathway (VSP) inhibitors. We review the incidence, mechanism, and strategies for management of TKI-induced HTN. We hope to provide clinicians with guidance on how to manage similar clinical scenarios. RECENT FINDINGS: Many of the newer VSP inhibitors are reviewed here, including cediranib, axitinib, pazopanib, and ponatinib...
June 21, 2018: Current Oncology Reports
Bing Yang, Shanshan Lan, Mélanie Dieudé, Jean-Paul Sabo-Vatasescu, Annie Karakeussian-Rimbaud, Julie Turgeon, Shijie Qi, Lakshman Gunaratnam, Natalie Patey, Marie-Josée Hébert
Background Ischemia-reperfusion injury (IRI) is a major risk factor for chronic renal failure. Here, we characterize the different modes of programmed cell death in the tubular and microvascular compartments during the various stages of IRI-induced AKI, and their relative importance to renal fibrogenesis. Methods We performed unilateral renal artery clamping for 30 minutes and contralateral nephrectomy in wild-type mice (C57BL/6) or caspase-3-/- mice. Results Compared with their wild-type counterparts, caspase-3-/- mice in the early stage of AKI had high urine cystatin C levels, tubular injury scores, and serum creatinine levels...
July 2018: Journal of the American Society of Nephrology: JASN
Francesco Romano, Alessandro Arrigo, Soon Wai Chʼng, Maurizio Battaglia Parodi, Maria Pia Manitto, Elisabetta Martina, Francesco Bandello, Paulo E Stanga
PURPOSE: To assess foveal and parafoveal vasculature at the superficial capillary plexus, deep capillary plexus, and choriocapillaris of patients with X-linked retinoschisis by means of optical coherence tomography angiography. METHODS: Six patients with X-linked retinoschisis (12 eyes) and seven healthy controls (14 eyes) were recruited and underwent complete ophthalmologic examination, including best-corrected visual acuity, dilated fundoscopy, and 3 × 3-mm optical coherence tomography angiography macular scans (DRI OCT Triton; Topcon Corp)...
June 5, 2018: Retina
Yuan Li, Quan Li, Chun-Shui Pan, Li Yan, Bai-He Hu, Yu-Ying Liu, Lei Yang, Ping Huang, Shao-Yang Zhao, Chuan-She Wang, Jing-Yu Fan, Xue-Mei Wang, Jing-Yan Han
Type 2 Diabetes mellitus (T2DM) is closely correlated with cognitive impairment and neurodegenerative disease. Bushen Huoxue (BSHX) is a compound Chinese medicine used clinically to treat diabetes-induced cognitive impairment. However, its underlying mechanisms remain unclear. In the present study, KKAy mice, a genetic model of type 2 diabetes with obesity and insulin resistant hyperglycemia, received a daily administration of BSHX for 12 weeks. Blood glucose was measured every 4 weeks. After 12 weeks, BSHX treatment significantly ameliorated the T2DM related insults, including the increased blood glucose, the impaired spatial memory, decreased cerebral blood flow (CBF), occurrence of albumin leakage, leukocyte adhesion and opening capillary rarefaction...
2018: Frontiers in Physiology
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