Uremic mouse model to study vascular calcification and "inflamm-aging".
Calcification
Cardiovascular
Chronic inflammation
Chronic renal insufficiency
Inflammation
Vascular calcification
Journal
Journal of molecular medicine (Berlin, Germany)
ISSN: 1432-1440
Titre abrégé: J Mol Med (Berl)
Pays: Germany
ID NLM: 9504370
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
19
11
2021
accepted:
05
07
2022
revised:
19
05
2022
pubmed:
3
8
2022
medline:
27
8
2022
entrez:
2
8
2022
Statut:
ppublish
Résumé
Calcification and chronic inflammation of the vascular wall is a high-risk factor for cardiovascular mortality, especially in patients with chronic uremia. For the reduction or prevention of rapid disease progression, no specific treatment options are currently available. This study aimed to evaluate an adenine-based uremic mouse model for studying medial vessel calcification and senescence-associated secretory phenotype (SASP) changes of aortic tissue to unravel molecular pathogenesis and provide a model for therapy testing. The dietary adenine administration induced a stable and similar degree of chronic uremia in DBA2/N mice with an increase of uremia blood markers such as blood urea nitrogen, calcium, creatinine, alkaline phosphatase, and parathyroid hormone. Also, renal fibrosis and crystal deposits were detected upon adenine feeding. The uremic condition is related to a moderate to severe medial vessel calcification and subsequent elastin disorganization. In addition, expression of osteogenic markers as Bmp-2 and its transcription factor Sox-9 as well as p21 as senescence marker were increased in uremic mice compared to controls. Pro-inflammatory uremic proteins such as serum amyloid A, interleukin (Il)-1β, and Il-6 increased. This novel model of chronic uremia provides a simple method for investigation of signaling pathways in vascular inflammation and calcification and therefore offers an experimental basis for the development of potential therapeutic intervention studies.
Identifiants
pubmed: 35916902
doi: 10.1007/s00109-022-02234-y
pii: 10.1007/s00109-022-02234-y
pmc: PMC9402761
doi:
Substances chimiques
Adenine
JAC85A2161
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1321-1330Informations de copyright
© 2022. The Author(s).
Références
Tolle M, Reshetnik A, Schuchardt M, Hohne M, van der Giet M (2015) Arteriosclerosis and vascular calcification: causes, clinical assessment and therapy. Eur J Clin Invest 45:976–985. https://doi.org/10.1111/eci.12493
doi: 10.1111/eci.12493
pubmed: 26153098
Leopold JA (2015) Vascular calcification: mechanisms of vascular smooth muscle cell calcification. Trends Cardiovasc Med 25:267–274. https://doi.org/10.1016/j.tcm.2014.10.021
doi: 10.1016/j.tcm.2014.10.021
pubmed: 25435520
Lanzer P, Hannan FM, Lanzer JD, Janzen J, Raggi P, Furniss D, Schuchardt M, Thakker R, Fok PW, Saez-Rodriguez J et al (2021) Medial arterial calcification: JACC state-of-the-art review. J Am Coll Cardiol 78:1145–1165. https://doi.org/10.1016/j.jacc.2021.06.049
doi: 10.1016/j.jacc.2021.06.049
pubmed: 34503684
Sanchis P, Ho CY, Liu Y, Beltran LE, Ahmad S, Jacob AP, Furmanik M, Laycock J, Long DA, Shroff R et al (2019) Arterial “inflammaging” drives vascular calcification in children on dialysis. Kidney Int 95:958–972. https://doi.org/10.1016/j.kint.2018.12.014
doi: 10.1016/j.kint.2018.12.014
pubmed: 30827513
pmcid: 6684370
Dai L, Qureshi AR, Witasp A, Lindholm B, Stenvinkel P (2019) Early vascular ageing and cellular senescence in chronic kidney disease. Comput Struct Biotechnol J 17:721–729. https://doi.org/10.1016/j.csbj.2019.06.015
doi: 10.1016/j.csbj.2019.06.015
pubmed: 31303976
pmcid: 6603301
Sperka T, Wang J, Rudolph KL (2012) DNA damage checkpoints in stem cells, ageing and cancer. Nat Rev 13:579–590. https://doi.org/10.1038/nrm3420
doi: 10.1038/nrm3420
Orjalo AV, Bhaumik D, Gengler BK, Scott GK, Campisi J (2009) Cell surface-bound IL-1alpha is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network. Proc Natl Acad Sci U S A 106:17031–17036. https://doi.org/10.1073/pnas.0905299106
doi: 10.1073/pnas.0905299106
pubmed: 19805069
pmcid: 2761322
Wen C, Yang X, Yan Z, Zhao M, Yue X, Cheng X, Zheng Z, Guan K, Dou J, Xu T et al (2013) Nalp3 inflammasome is activated and required for vascular smooth muscle cell calcification. Int J Cardiol 168:2242–2247. https://doi.org/10.1016/j.ijcard.2013.01.211
doi: 10.1016/j.ijcard.2013.01.211
pubmed: 23453445
Hegner B, Schaub T, Janke D, Zickler D, Lange C, Girndt M, Jankowski J, Schindler R, Dragun D (2018) Targeting proinflammatory cytokines ameliorates calcifying phenotype conversion of vascular progenitors under uremic conditions in vitro. Sci Rep 8:12087. https://doi.org/10.1038/s41598-018-30626-z
doi: 10.1038/s41598-018-30626-z
pubmed: 30108259
pmcid: 6092400
Herrmann J, Gummi MR, Xia M, van der Giet M, Tolle M, Schuchardt M (2021) Vascular calcification in rodent models-keeping track with an extented method assortment. Biology (Basel). https://doi.org/10.3390/biology10060459
doi: 10.3390/biology10060459
pubmed: 34681166
pmcid: 8533629
Herrmann J, Babic M, Tolle M, van der Giet M, Schuchardt M (2020) Research models for studying vascular calcification. Int J Mol Sci 21:2204. https://doi.org/10.3390/ijms21062204
doi: 10.3390/ijms21062204
pmcid: 7139511
Shobeiri N, Pang J, Adams MA, Holden RM (2013) Cardiovascular disease in an adenine-induced model of chronic kidney disease: the temporal link between vascular calcification and haemodynamic consequences. J Hypertens 31:160–168. https://doi.org/10.1097/HJH.0b013e32835b15bb
doi: 10.1097/HJH.0b013e32835b15bb
pubmed: 23183279
Santana AC, Degaspari S, Catanozi S, Delle H, de Sa LL, Silva C, Blanco P, Solez K, Scavone C, Noronha IL (2013) Thalidomide suppresses inflammation in adenine-induced CKD with uraemia in mice. Nephrol Dial Transplant 28:1140–1149. https://doi.org/10.1093/ndt/gfs569
doi: 10.1093/ndt/gfs569
pubmed: 23345625
Yoshida T, Yamashita M, Horimai C, Hayashi M (2017) Smooth muscle-selective nuclear factor-kappaB inhibition reduces phosphate-induced arterial medial calcification in mice with chronic kidney disease. J Am Heart Assoc. https://doi.org/10.1161/JAHA.117.007248
doi: 10.1161/JAHA.117.007248
pubmed: 29146611
pmcid: 5721793
Oe Y, Mitsui S, Sato E, Shibata N, Kisu K, Sekimoto A, Miyazaki M, Sato H, Ito S, Takahashi N (2021) Lack of endothelial nitric oxide synthase accelerates ectopic calcification in uremic mice fed an adenine and high phosphorus diet. Am J Pathol 191:283–293. https://doi.org/10.1016/j.ajpath.2020.10.012
doi: 10.1016/j.ajpath.2020.10.012
pubmed: 33159888
Nguyen-Yamamoto L, Tanaka KI, St-Arnaud R, Goltzman D (2019) Vitamin D-regulated osteocytic sclerostin and BMP2 modulate uremic extraskeletal calcification. JCI Insight. https://doi.org/10.1172/jci.insight.126467
doi: 10.1172/jci.insight.126467
pubmed: 31292298
pmcid: 6629247
Tani T, Orimo H, Shimizu A, Tsuruoka S (2017) Development of a novel chronic kidney disease mouse model to evaluate the progression of hyperphosphatemia and associated mineral bone disease. Sci Rep 7:2233. https://doi.org/10.1038/s41598-017-02351-6
doi: 10.1038/s41598-017-02351-6
pubmed: 28533541
pmcid: 5440375
El-Abbadi MM, Pai AS, Leaf EM, Yang HY, Bartley BA, Quan KK, Ingalls CM, Liao HW, Giachelli CM (2009) Phosphate feeding induces arterial medial calcification in uremic mice: role of serum phosphorus, fibroblast growth factor-23, and osteopontin. Kidney Int 75:1297–1307. https://doi.org/10.1038/ki.2009.83
doi: 10.1038/ki.2009.83
pubmed: 19322138
pmcid: 2799244
Pai A, Leaf EM, El-Abbadi M, Giachelli CM (2011) Elastin degradation and vascular smooth muscle cell phenotype change precede cell loss and arterial medial calcification in a uremic mouse model of chronic kidney disease. Am J Pathol 178:764–773. https://doi.org/10.1016/j.ajpath.2010.10.006
doi: 10.1016/j.ajpath.2010.10.006
pubmed: 21281809
pmcid: 3069837
Lau WL, Linnes M, Chu EY, Foster BL, Bartley BA, Somerman MJ, Giachelli CM (2013) High phosphate feeding promotes mineral and bone abnormalities in mice with chronic kidney disease. Nephrol Dial Transplant 28:62–69. https://doi.org/10.1093/ndt/gfs333
doi: 10.1093/ndt/gfs333
pubmed: 23045434
Schuchardt M, Tolle M, Prufer J, Prufer N, Huang T, Jankowski V, Jankowski J, Zidek W, van der Giet M (2012) Uridine adenosine tetraphosphate activation of the purinergic receptor P2Y enhances in vitro vascular calcification. Kidney Int 81:256–265. https://doi.org/10.1038/ki.2011.326
doi: 10.1038/ki.2011.326
pubmed: 21956191
Prufer J, Schuchardt M, Tolle M, Prufer N, Hohne M, Zidek W, van der Giet M (2014) Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: induction of mineralization. PLoS ONE 9:e101709. https://doi.org/10.1371/journal.pone.0101709
doi: 10.1371/journal.pone.0101709
pubmed: 25029363
pmcid: 4100760
Tolle M, Huang T, Schuchardt M, Jankowski V, Prufer N, Jankowski J, Tietge UJ, Zidek W, van der Giet M (2012) High-density lipoprotein loses its anti-inflammatory capacity by accumulation of pro-inflammatory-serum amyloid A. Cardiovasc Res 94:154–162. https://doi.org/10.1093/cvr/cvs089
doi: 10.1093/cvr/cvs089
pubmed: 22328092
Price PA, Roublick AM, Williamson MK (2006) Artery calcification in uremic rats is increased by a low protein diet and prevented by treatment with ibandronate. Kidney Int 70:1577–1583. https://doi.org/10.1038/sj.ki.5001841
doi: 10.1038/sj.ki.5001841
pubmed: 16955099
Du F, Higginbotham DA, White BD (2000) Food intake, energy balance and serum leptin concentrations in rats fed low-protein diets. J Nutr 130:514–521
doi: 10.1093/jn/130.3.514
Fang Y, Ginsberg C, Sugatani T, Monier-Faugere MC, Malluche H, Hruska KA (2014) Early chronic kidney disease-mineral bone disorder stimulates vascular calcification. Kidney Int 85:142–150. https://doi.org/10.1038/ki.2013.271
doi: 10.1038/ki.2013.271
pubmed: 23884339
Mazzaccara C, Labruna G, Cito G, Scarfo M, De Felice M, Pastore L, Sacchetti L (2008) Age-related reference intervals of the main biochemical and hematological parameters in C57BL/6J, 129SV/EV and C3H/HeJ mouse strains. PLoS ONE 3:e3772. https://doi.org/10.1371/journal.pone.0003772
doi: 10.1371/journal.pone.0003772
pubmed: 19020657
pmcid: 2582346
Tani T, Fujiwara M, Orimo H, Shimizu A, Narisawa S, Pinkerton AB, Millan JL, Tsuruoka S (2020) Inhibition of tissue-nonspecific alkaline phosphatase protects against medial arterial calcification and improves survival probability in the CKD-MBD mouse model. J Pathol 250:30–41. https://doi.org/10.1002/path.5346
doi: 10.1002/path.5346
pubmed: 31509234
Rodier F, Coppe JP, Patil CK, Hoeijmakers WA, Munoz DP, Raza SR, Freund A, Campeau E, Davalos AR, Campisi J (2009) Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol 11:973–979. https://doi.org/10.1038/ncb1909
doi: 10.1038/ncb1909
pubmed: 19597488
pmcid: 2743561
Freund A, Orjalo AV, Desprez PY, Campisi J (2010) Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med 16:238–246. https://doi.org/10.1016/j.molmed.2010.03.003
doi: 10.1016/j.molmed.2010.03.003
pubmed: 20444648
pmcid: 2879478
Nakano-Kurimoto R, Ikeda K, Uraoka M, Nakagawa Y, Yutaka K, Koide M, Takahashi T, Matoba S, Yamada H, Okigaki M et al (2009) Replicative senescence of vascular smooth muscle cells enhances the calcification through initiating the osteoblastic transition. Am J Physiol Heart Circ Physiol 297:H1673-1684. https://doi.org/10.1152/ajpheart.00455.2009
doi: 10.1152/ajpheart.00455.2009
pubmed: 19749165
Burton DG, Giles PJ, Sheerin AN, Smith SK, Lawton JJ, Ostler EL, Rhys-Williams W, Kipling D, Faragher RG (2009) Microarray analysis of senescent vascular smooth muscle cells: a link to atherosclerosis and vascular calcification. Exp Gerontol 44:659–665. https://doi.org/10.1016/j.exger.2009.07.004
doi: 10.1016/j.exger.2009.07.004
pubmed: 19631729
Lee CT, Chua S, Hsu CY, Tsai YC, Ng HY, Kuo CC, Wu CH, Chen TC, Chiu TT, Lee YT (2013) Biomarkers associated with vascular and valvular calcification in chronic hemodialysis patients. Dis Markers 34:229–235. https://doi.org/10.3233/DMA-130965
doi: 10.3233/DMA-130965
pubmed: 23396289
pmcid: 3810241
Simic-Ogrizovic S, Dopsaj V, Bogavac-Stanojevic N, Obradovic I, Stosovic M, Radovic M (2009) Serum amyloid-A rather than C-reactive protein is a better predictor of mortality in hemodialysis patients. Tohoku J Exp Med 219:121–127. https://doi.org/10.1620/tjem.219.121
doi: 10.1620/tjem.219.121
pubmed: 19776529
Barreto DV, Barreto FC, Liabeuf S, Temmar M, Lemke HD, Tribouilloy C, Choukroun G, Vanholder R, Massy ZA, Work EUT, G, (2010) Plasma interleukin-6 is independently associated with mortality in both hemodialysis and pre-dialysis patients with chronic kidney disease. Kidney Int 77:550–556. https://doi.org/10.1038/ki.2009.503
doi: 10.1038/ki.2009.503
pubmed: 20016471
Ridker PM (2016) From C-reactive protein to interleukin-6 to interleukin-1: moving upstream to identify novel targets for atheroprotection. Circ Res 118:145–156. https://doi.org/10.1161/CIRCRESAHA.115.306656
doi: 10.1161/CIRCRESAHA.115.306656
pubmed: 26837745
pmcid: 4793711
Herrmann J, Xia M, Gummi MR, Greco A, Schacke A, van der Giet M, Tolle M, Schuchardt M (2021) Stressor-Induced “inflammaging” of vascular smooth muscle cells via Nlrp3-mediated pro-inflammatory auto-loop. Frontiers in cardiovascular medicine 8:752305. https://doi.org/10.3389/fcvm.2021.752305
doi: 10.3389/fcvm.2021.752305
pubmed: 34988126
pmcid: 8720922
Feng H, Wang JY, Yu B, Cong X, Zhang WG, Li L, Liu LM, Zhou Y, Zhang CL, Gu PL et al (2019) Peroxisome proliferator-activated receptor-gamma coactivator-1alpha inhibits vascular calcification through sirtuin 3-mediated reduction of mitochondrial oxidative stress. Antioxid Redox Signal 31:75–91. https://doi.org/10.1089/ars.2018.7620
doi: 10.1089/ars.2018.7620
pubmed: 30829051
De Schutter TM, Behets GJ, Geryl H, Peter ME, Steppan S, Gundlach K, Passlick-Deetjen J, D’Haese PC, Neven E (2013) Effect of a magnesium-based phosphate binder on medial calcification in a rat model of uremia. Kidney Int 83:1109–1117. https://doi.org/10.1038/ki.2013.34
doi: 10.1038/ki.2013.34
pubmed: 23486515
pmcid: 3674404