scholarly journals Cathepsin K Deficiency Impaired Ischemia-Induced Neovascularization in Aged Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xueling Yue ◽  
Haiying Jiang ◽  
Ying Xu ◽  
Manli Xia ◽  
Xian-Wu Cheng
Keyword(s):  
Blood Flow ◽  
Flow Analysis ◽  
Cathepsin K ◽  
Cellular Functions ◽  
Aged Mice ◽  
Blood Flow Ratio ◽  
K Deficiency ◽  
Signaling Activation ◽  
Endothelial Growth Factor

Background. Aging is a major risk factor for cardiovascular disease. Cysteine protease cathepsin K (CatK) has been implicated in the process of angiogenesis, but the exact roles of individual CatK in vessel formation during aging are poorly understood. Methods and Results. To study the putative role of CatK in ischemia-induced angiogenesis, we applied a hindlimb ischemia model to aged wild-type (CatK+/+) and CatK-deficient (CatK−/−) mice. A serial laser Doppler blood-flow analysis revealed that the recovery of the ischemic/normal blood-flow ratio in the aged CatK−/−mice was impaired throughout the follow-up period. On postoperative day 14, CatK deficiency had also impaired capillary formation. CatK deficiency reduced the levels of cleaved Notch1, phospho-Akt, and/or vascular endothelial growth factor (VEGF) proteins in the ischemic muscles and bone marrow-derived c-Kit+ cells. A flow cytometry analysis revealed that CatK deficiency reduced the numbers of endothelial progenitor cell (EPC)-like CD31+/c-Kit+ cells in the peripheral blood as well as the ischemic vasculature. In vitro experiments, CatK−/− impaired bone-derived c-Kit+ cellular functions (migration, invasion, proliferation, and tubulogenesis) in aged mice. Our findings demonstrated that aging impaired the ischemia-induced angiogenesis associated with the reductions of the production and mobilization of CD31+/c-Kit+ cells in mice. Conclusions. These findings established that the impairment of ischemia-induced neovascularization in aged CatK−/− mice is due, at least in part, to the reduction of EPC mobilization and the homing of the cells into vasculature that is associated with the impairment of Notch1 signaling activation at advanced ages.

Hemodynamic effects of intracoronary VEGF delivery: evidence of tachyphylaxis and NO dependence of response

1997 ◽  
Vol 273 (3) ◽  
pp. H1317-H1323 ◽  
Author(s):  
J. J. Lopez ◽  
R. J. Laham ◽  
J. P. Carrozza ◽  
M. Tofukuji ◽  
F. W. Sellke ◽  
...  
Keyword(s):  
Blood Flow ◽  
Diastolic Pressure ◽  
Rapid Development ◽  
Left Ventricular ◽  
No Production ◽  
Vascular Endothelial ◽  
Hemodynamic Effects ◽  
Endothelial Growth Factor ◽  
Dose Dependent Increase

Vascular endothelial growth factor (VEGF) has been utilized to improve blood flow in the setting of myocardial or peripheral vascular ischemia. In this investigation we studied the hemodynamic effects of intracoronary VEGF administration. Hemodynamic parameters and Doppler flow wire recordings from the left anterior descending coronary artery were measured after intracoronary infusion of VEGF (1, 10, and 100 micrograms) in 28 intubated pigs. Additional studies were performed using an in vitro isolated microvessel preparation. VEGF produced a highly significant dose-dependent increase in coronary blood flow (maximal 3.51 +/- 0.85-fold) in the absence of significant changes in epicardial artery diameter, a decline in mean arterial pressure (maximal 43%), and a decrease in left ventricular end-diastolic pressure (maximal 52%), all of which could be inhibited by pretreatment with NG-nitro-L-arginine. The increase in coronary flow seen with 10 or 100 micrograms VEGF was significantly greater than the maximal vasodilation achieved with serotonin or nitroglycerin and was equivalent to a maximal adenosine response. In summary, VEGF stimulates nitric oxide (NO)-dependent dilation of coronary microvessels, and repeat administrations of VEGF resulted in rapid development of tachyphylaxis to VEGF as well as serotonin, but not to nitroglycerin or adenosine, which appeared to be secondary to impaired NO production.

scholarly journals Analisis Interaksi Aliran Darah dan Pembuluh Serta Pengaruh Kebebasan Mesh Pada Simulasi Hemodinamik Berbasis Metode Elemen Hingga

2020 ◽  
Vol 4 (2) ◽  
pp. 54
Author(s):  
Narendra Kurnia Putra ◽  
Bonfilio Nainggolan ◽  
Johanna Muliany ◽  
S Suprijanto
Keyword(s):  
Blood Flow ◽  
Computational Simulation ◽  
Flow Analysis ◽  
Flow Simulation ◽  
Vascular Wall ◽  
Wall Displacement ◽  
Vascular Flow ◽  
Mesh Independence ◽  
Significant Difference

Cardiovascular diseases are the world’s leading cause of death with significant death rates caused by abnormalities in vessels such as aneurysms and stenosis. These conditions can potentially cause blockage and thinning of vessels which may lead to heart attack, stroke, and bleedings. Recently, computational simulation methods are frequently used in blood flow analysis. These methods are frequently used in vascular fluid dynamics analysis which relate to the origin of a disease, efficacy prediction in installation of therapeutic instruments and complements the in vitro studies. This article presents an example of a simple vascular simulation to study the effect of blood flow with respect to vascular wall displacement. Furthermore, this research shows the importance of formal CFD pre-processing such as mesh independence testing which influences the simlation accuracy as well as vascular flow prediction and its effects on vascular wall displacement. In this research, it is concluded that the number of mesh elements affects the accuracy of vascular wall shear stress (WSS) calculations with average WSS difference of 0.8 Pa with no significant difference in wall displacement values. An average WSS of 1.95 Pa and a wall displacement of 5.7 µm are obtained from the blood flow simulation in this study.

scholarly journals Gender differences affect blood flow recovery in a mouse model of hindlimb ischemia

2011 ◽  
Vol 300 (6) ◽  
pp. H2027-H2034 ◽  
Author(s):  
XinZhi Peng ◽  
Jinsong Wang ◽  
Roberta M. Lassance-Soares ◽  
Amir H. Najafi ◽  
Subeena Sood ◽  
...  
Keyword(s):  
Blood Flow ◽  
Smooth Muscle Actin ◽  
Gender Effects ◽  
Endothelial Cell Proliferation ◽  
Hindlimb Ischemia ◽  
Ischemic Tissue ◽  
Flow Restoration ◽  
Endothelial Growth Factor ◽  
Endothelial Nitric Oxide

Blood flow restoration to ischemic tissue is affected by various risk factors. The aim of this study was to examine gender effects on arteriogenesis and angiogenesis in a mouse ischemic hindlimb model. C57BL/6J mice were subjected to unilateral hindlimb ischemia. Flow recovery was less and hindlimb use impairment was greater in females. No gender difference in vessel number was found at baseline, although 7 days postsurgery females had fewer α-smooth muscle actin-positive vessels in the midpoint of the adductor region. Females had higher hindlimb vascular resistance, were less responsive to vasodilators, and were more sensitive to vasoconstrictors postligation. Western blotting showed that females had higher baseline levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) in the calf, while 7 days postligation males had higher levels of VEGF, eNOS, and phosphorylated vasodilator stimulated phosphoprotein. Females had less angiogenesis in a Matrigel plug assay and less endothelial cell proliferation in vitro. Females have impaired recovery of flow, a finding presumably caused by multiple factors including decreased collateral remodeling, less angiogenesis, impaired vasodilator response, and increased vasoconstrictor activity; our results also suggest the possibility that new collateral formation, from capillaries, is impaired in females.

scholarly journals Increased Bone Resorption during Lactation in Pycnodysostosis

2021 ◽  
Vol 22 (4) ◽  
pp. 1810
Author(s):  
Ineke D.C. Jansen ◽  
Socrates E. Papapoulos ◽  
Nathalie Bravenboer ◽  
Teun J. de Vries ◽  
Natasha M. Appelman-Dijkstra
Keyword(s):  
Bone Resorption ◽  
Cathepsin K ◽  
Collagen Type I ◽  
Type I ◽  
Lactation Period ◽  
Blood Monocytes ◽  
Lactating Women ◽  
Before And After ◽  
K Deficiency

Pycnodysostosis, a rare autosomal recessive skeletal dysplasia, is caused by a deficiency of cathepsin K. Patients have impaired bone resorption in the presence of normal or increased numbers of multinucleated, but dysfunctional, osteoclasts. Cathepsin K degrades collagen type I and generates N-telopeptide (NTX) and the C-telopeptide (CTX) that can be quantified. Levels of these telopeptides are increased in lactating women and are associated with increased bone resorption. Nothing is known about the consequences of cathepsin K deficiency in lactating women. Here we present for the first time normalized blood and CTX measurements in a patient with pycnodysostosis, exclusively related to the lactation period. In vitro studies using osteoclasts derived from blood monocytes during lactation and after weaning further show consistent bone resorption before and after lactation. Increased expression of cathepsins L and S in osteoclasts derived from the lactating patient suggests that other proteinases could compensate for the lack of cathepsin K during the lactation period of pycnodysostosis patients.

In vitro blood flow analysis using magnetic resonance angiography

2016 ◽  
Vol 32 ◽  
pp. 305 ◽  
Author(s):  
Kazerou Aspasia ◽  
Patatoukas George ◽  
Argiropoulos George ◽  
Efstathopoulos Efstathios
Keyword(s):  
Blood Flow ◽  
Magnetic Resonance ◽  
Magnetic Resonance Angiography ◽  
Flow Analysis ◽  
Blood Flow Analysis

Correlation Between Cellular Functions and Morphological Changes of Human Trophoblast in Vitro

1975 ◽  
Vol 33 ◽  
pp. 600-601
Author(s):  
John C. Garancis ◽  
Robert O. Hussa ◽  
Michael T. Story ◽  
Donald Yorde ◽  
Roland A. Pattillo
Keyword(s):  
Electron Microscopy ◽  
Cellular Proliferation ◽  
Morphological Changes ◽  
Culture Fluid ◽  
Cellular Functions ◽  
Human Trophoblast ◽  
Transmission Electron ◽  
Marked Activity ◽  
Malignant Trophoblast

Human malignant trophoblast cells in continuous culture were incubated for 3 days in medium containing 1 mM N6-O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) and 1 mM theophylline. The culture fluid was replenished daily. Stimulated cultures secreted many times more chorionic gonadotropin and estrogens than did control cultures in the absence of increased cellular proliferation. Scanning electron microscopy revealed remarkable surface changes of stimulated cells. Control cells (not stimulated) were smooth or provided with varying numbers of microvilli (Fig. 1). The latter, usually, were short and thin. The surface features of stimulated cells were considerably different. There was marked increase of microvilli which appeared elongated and thick. Many cells were covered with confluent polypoid projections (Fig. 2). Transmission electron microscopy demonstrated marked activity of cytoplasmic organelles. Mitochondria were increased in number and size; some giant forms with numerous cristae were observed.

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