Aortic stiffness is associated with vascular calcification and remodeling in a chronic kidney disease rat model

2011 ◽  
Vol 300 (6) ◽  
pp. F1431-F1436 ◽  
Author(s):  
Keith Ng ◽  
Cara M. Hildreth ◽  
Jacqueline K. Phillips ◽  
Alberto P. Avolio
Keyword(s):  
Chronic Kidney Disease ◽  
Smooth Muscle ◽  
Kidney Disease ◽  
Wall Thickness ◽  
Vascular Remodeling ◽  
Aortic Stiffness ◽  
Aortic Wall ◽  
Strong Predictor ◽  
Aortic Calcification ◽  
Aortic Wall Thickness

Increased aortic pulse-wave velocity (PWV) reflects increased arterial stiffness and is a strong predictor of cardiovascular risk in chronic kidney disease (CKD). We examined functional and structural correlations among PWV, aortic calcification, and vascular remodeling in a rodent model of CKD, the Lewis polycystic kidney (LPK) rat. Hemodynamic parameters and beat-to-beat aortic PWV were recorded in urethane-anesthetized animals [12-wk-old hypertensive female LPK rats ( n = 5)] before the onset of end-stage renal disease and their age- and sex-matched normotensive controls (Lewis, n = 6). Animals were euthanized, and the aorta was collected to measure calcium content by atomic absorption spectrophotometry. A separate cohort of animals ( n = 5/group) were anesthetized with pentobarbitone sodium and pressure perfused with formalin, and the aorta was collected for histomorphometry, which allowed calculation of aortic wall thickness, medial cross-sectional area (MCSA), elastic modulus (EM), and wall stress (WS), size and density of smooth muscle nuclei, and relative content of lamellae, interlamellae elastin, and collagen. Mean arterial pressure (MAP) and PWV were significantly greater in the LPK compared with Lewis (72 and 33%, respectively) animals. The LPK group had 6.8-fold greater aortic calcification, 38% greater aortic MCSA, 56% greater EM/WS, 13% greater aortic wall thickness, 21% smaller smooth muscle cell area, and 20% less elastin density with no difference in collagen fiber density. These findings demonstrate vascular remodeling and increased calcification with a functional increase in PWV and therefore aortic stiffness in hypertensive LPK rats.

Abstract 641: Hypotrophic Vascular Remodeling Associates With Vascular Calcification in vivo in Vitamin D 3 -stimulated Leptin-deficient ob/ob Mice

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Luciana S Carmo ◽  
Youri E Almeida ◽  
Marcel Liberman
Keyword(s):  
Cardiovascular Disease ◽  
Vitamin D ◽  
Vascular Calcification ◽  
Wall Thickness ◽  
Vascular Remodeling ◽  
Aortic Wall ◽  
Wall Area ◽  
Aortic Wall Thickness ◽  
Vitamin D 3

Vascular calcification may determine arterial flow imbalance through increasing vascular rigidity and Windkessel effect, frequently occurring in diabetes. Vascular remodeling, considered an adaptive response of the vessel to specific stimuli, may associate with calcification and participate in pathophysiology of cardiovascular disease. In order to further investigate the intersection between pathophysiology of vascular calcification and vascular remodeling, we hypothesized that leptin-deficient ob/ob mice, demonstrate increased vascular remodeling and vascular calcifying response to Vitamin D 3 in vivo compared to C57BL/6 (C57) mice. We injected C57 and ob/ob mice with Vitamin D 3 8x10 4 IU (VitD) daily or saline 0.9% ip. (Cont) for 14 days and for 21 days. Results are showed as Mean±SEM. We considered statistically significant if p<.05 after ANOVA (Newman-Keuls). After 14d, o b/ob VitD aorta decreased aortic wall thickness (24.3±0.4μm) versus ob/ob Cont (29.7±1.3μm), vs. C57VitD (34.4±0.6μm) and vs. C57Cont (39±1.3μm), p<.05 n=6. After 21d, we also showed that ob/ob VitD decreased aortic wall thickness (25.4±0.5μm) vs. ob/ob Cont (29.7±1.3μm) and vs. C57Cont (39.0±1.3μm), p<.05 n=3. Moreover, o b/ob VitD decreased vessel wall area (VWA)= 79120±3957μm 2 vs. ob/ob Cont=85310±4593μm 2 and vs. C57Cont=96970±6719μm 2 after 14d (n=6) and also after 21d ( ob/ob VitD=72090±3268μm 2 vs. ob/ob Cont=85310±4593μm 2 (n=3). On contrary, C57VitD did not change VWA. Coincidently, ob/ob VitD increased vascular calcification after 14d (total Ca ++ area burden=4548.2μm 2 , n=6) and after 21d (total Ca ++ area burden=2212.88 μm 2 , n=3) respectively. C57VitD and C57Cont did not calcify (n=6). Together with increased VWA loss and calcification, ob/ob VitD also showed augmented elastolysis and fibrosis. Nevertheless, hypotrophic remodeling did not determine any change in vascular lumen area ( ob/ob VitD=208300±24810μm 2 ; ob/ob Cont=207300±22740μm 2 , C57VitD=196800±22120μm 2 and C57Cont=225400±17960μm 2 ) after 14d in this model. Vascular remodeling associated with calcification and other architectural changes of the vascular wall may bring important insights for investigating human cardiovascular disease in obese and insulin resistant background.

AB0967 Determinants of Aortic Wall Thickness in Patients without Aortitis: A Computed Tomography-Based Study: Table 1

2014 ◽  
Vol 73 (Suppl 2) ◽  
pp. 1119.3-1120
Author(s):  
A. Nakhleh ◽  
D. Rimar ◽  
I. Rukhkyan ◽  
V. Wolfson ◽  
I. Rosner ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Wall Thickness ◽  
Aortic Wall ◽  
Aortic Wall Thickness

scholarly journals Vascular Remodeling and Arterial Calcification Are Directly Mediated by S100A12 (EN-RAGE) in Chronic Kidney Disease

2011 ◽  
Vol 33 (3) ◽  
pp. 250-259 ◽  
Author(s):  
Joseph Gawdzik ◽  
Liby Mathew ◽  
Gene Kim ◽  
Tipu S. Puri ◽  
Marion A. Hofmann Bowman
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Remodeling ◽  
Arterial Calcification

scholarly journals Effect of MgCl2 and GdCl3 on ORAI1 Expression and Store-Operated Ca2+ Entry in Megakaryocytes

2021 ◽  
Vol 22 (7) ◽  
pp. 3292
Author(s):  
Kuo Zhou ◽  
Xuexue Zhu ◽  
Ke Ma ◽  
Jibin Liu ◽  
Bernd Nürnberg ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Transcription Factor ◽  
Smooth Muscle ◽  
Kidney Disease ◽  
Protein Abundance ◽  
Rt Pcr ◽  
Calcium Sensing Receptor ◽  
Transcript Levels ◽  
Calcium Sensing ◽  
Store Depletion

In chronic kidney disease, hyperphosphatemia upregulates the Ca2+ channel ORAI and its activating Ca2+ sensor STIM in megakaryocytes and platelets. ORAI1 and STIM1 accomplish store-operated Ca2+ entry (SOCE) and play a key role in platelet activation. Signaling linking phosphate to upregulation of ORAI1 and STIM1 includes transcription factor NFAT5 and serum and glucocorticoid-inducible kinase SGK1. In vascular smooth muscle cells, the effect of hyperphosphatemia on ORAI1/STIM1 expression and SOCE is suppressed by Mg2+ and the calcium-sensing receptor (CaSR) agonist Gd3+. The present study explored whether sustained exposure to Mg2+ or Gd3+ interferes with the phosphate-induced upregulation of NFAT5, SGK1, ORAI1,2,3, STIM1,2 and SOCE in megakaryocytes. To this end, human megakaryocytic Meg-01 cells were treated with 2 mM ß-glycerophosphate for 24 h in the absence and presence of either 1.5 mM MgCl2 or 50 µM GdCl3. Transcript levels were estimated utilizing q-RT-PCR, protein abundance by Western blotting, cytosolic Ca2+ concentration ([Ca2+]i) by Fura-2 fluorescence and SOCE from the increase in [Ca2+]i following re-addition of extracellular Ca2+ after store depletion with thapsigargin (1 µM). As a result, Mg2+ and Gd3+ upregulated CaSR and blunted or virtually abolished the phosphate-induced upregulation of NFAT5, SGK1, ORAI1,2,3, STIM1,2 and SOCE in megakaryocytes. In conclusion, Mg2+ and the CaSR agonist Gd3+ interfere with phosphate-induced dysregulation of [Ca2+]i in megakaryocytes.

scholarly journals Validation of semiautomated and locally resolved aortic wall thickness measurements from computed tomography

2015 ◽  
Vol 61 (4) ◽  
pp. 1034-1040 ◽  
Author(s):  
Eric K. Shang ◽  
Eric Lai ◽  
Alison M. Pouch ◽  
Robin Hinmon ◽  
Robert C. Gorman ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Wall Thickness ◽  
Aortic Wall ◽  
Aortic Wall Thickness ◽  
Thickness Measurements

Maternal undernutrition reduces aortic wall thickness and elastin content in offspring rats without altering endothelial function

2006 ◽  
Vol 111 (4) ◽  
pp. 281-287 ◽  
Author(s):  
Michael R. Skilton ◽  
Alison K. Gosby ◽  
Ben J. Wu ◽  
Lisa M. L. Ho ◽  
Roland Stocker ◽  
...  
Keyword(s):  
Wall Thickness ◽  
Aortic Wall ◽  
Infant Nutrition ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Organ Bath ◽  
High Fat ◽  
Maternal Undernutrition ◽  
Low Protein ◽  
Aortic Wall Thickness

Epidemiological studies suggest a link between fetal/early infant nutrition and adult coronary artery disease. In the present study, we examined the effects of altering nutrition during gestation, lactation and juvenile life on aortic structure and function in rats. Wistar rat dams were fed either a control or low-protein diet throughout pregnancy, or a low-protein diet for the final 7 days of gestation only. At 21 days post-partum, male pups were weaned on to a control, low-protein or high-fat diet. At 12 weeks, the offspring rats were killed. In 46 rats, aortic sections were mounted and stained to assess media thickness and elastin content. In a further 38 rats, aortic rings were suspended in an organ bath and vascular reactivity was tested with dose–response curves to the endothelium-dependent dilator acetylcholine and the endothelium-independent dilator sodium nitroprusside. Rats exposed to maternal protein restriction while in utero had a significantly decreased aortic wall thickness compared with control rats (P=0.005). Total elastin content of the aorta was also decreased by both maternal low-protein (P=0.02) and early postnatal low-protein (P=0.01) diets. Neither maternal nor postnatal low-protein or high-fat diets, however, resulted in any significant changes in arterial dilator function. In conclusion, fetal undernutrition in rats, induced via a maternal low-protein diet, causes a decrease in aortic wall thickness and elastin content without altering aortic dilator function. These changes in vascular structure may amplify aging-related changes to the vasculature and contribute to the pathophysiology of the putative link between impaired fetal growth and adult cardiovascular disease.

scholarly journals Aortic Stiffness Is Independently Associated With Rate of Renal Function Decline in Chronic Kidney Disease Stages 3 and 4

Hypertension ◽  
2010 ◽  
Vol 55 (5) ◽  
pp. 1110-1115 ◽  
Author(s):  
Martin L. Ford ◽  
Laurie A. Tomlinson ◽  
Thomas P.E. Chapman ◽  
Chakravarthi Rajkumar ◽  
Stephen G. Holt
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Aortic Stiffness ◽  
Renal Function Decline ◽  
Disease Stages
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