Skip to main content
Erschienen in: Netherlands Heart Journal 5/2009

01.05.2009 | original article

Renal failure induces telomere shortening in the rat heart

verfasst von: L. S. Wong, W. A. Windt, A. J. Roks, R. P. van Dokkum, R. G. Schoemaker, D. de Zeeuw, R. H. Henning

Erschienen in: Netherlands Heart Journal | Ausgabe 5/2009

Einloggen, um Zugang zu erhalten

Abstract

BackgroundRenal failure aggravates pathological cardiac remodelling induced by myocardial infarction (MI). Cardiac remodelling is associated with telomere shortening, a marker for biological ageing. We investigated whether mild and severe renal failure shorten cardiac telomeres and excessively shorten telomeres after MI.
MethodsRats were subjected to sham, unilateral (UNX) or 5/6th nephrectomy (5/6NX) to induce none, mild or severe renal failure. MI was induced by left coronary artery ligation. Renal function parameters and blood pressure were measured. DNA was isolated from non-infarcted cardiac tissue. Telomere length was assessed by quantitative polymerase chain reaction (PCR).
ResultsProteinuria was unchanged in UNX and MI compared with control, but strongly increased in 5/6NX, UNX+MI and 5/6NX+MI. Serum creatinine levels were increased fourfold in 5/6NX and tenfold in 5/6NX+MI. 5/6NX and groups with both renal failure and MI showed an approximate 20% reduction of telomere length, similar to the MI group. No excess telomere shortening was observed in hearts from rats with renal ablation after MI.
ConclusionSevere renal failure, but not mild renal failure, leads to shortening of cardiac telomeres to a similar extent as found after MI. Renal failure did not induce excessive telomere shortening after MI. (Neth Heart J 2009;17:190–4.)
Literatur
1.
Zurück zum Zitat Weiner DE, Tighiouart H, Amin MG, Stark PC, MacLeod B, Griffith JL, et al. Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies. J Am Soc Nephrol 2004;15:1307–15. Weiner DE, Tighiouart H, Amin MG, Stark PC, MacLeod B, Griffith JL, et al. Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies. J Am Soc Nephrol 2004;15:1307–15.
2.
Zurück zum Zitat Amann K, Kronenberg G, Gehlen F, Wessels S, Orth S, Munter K, et al. Cardiac remodelling in experimental renal failure – an immunohistochemical study. Nephrol Dial Transplant 1998;13: 1958–66. Amann K, Kronenberg G, Gehlen F, Wessels S, Orth S, Munter K, et al. Cardiac remodelling in experimental renal failure – an immunohistochemical study. Nephrol Dial Transplant 1998;13: 1958–66.
3.
Zurück zum Zitat Blackburn EH. Switching and signaling at the telomere. Cell 2001; 106:661–73. Blackburn EH. Switching and signaling at the telomere. Cell 2001; 106:661–73.
4.
Zurück zum Zitat Chan SR, Blackburn EH. Telomeres and telomerase. Philos Trans R Soc Lond B Biol Sci 2004;359:109–21. Chan SR, Blackburn EH. Telomeres and telomerase. Philos Trans R Soc Lond B Biol Sci 2004;359:109–21.
5.
Zurück zum Zitat Artandi SE. Telomeres, telomerase, and human disease. N Engl J Med 2006;355:1195–7. Artandi SE. Telomeres, telomerase, and human disease. N Engl J Med 2006;355:1195–7.
6.
Zurück zum Zitat Oh H, Wang SC, Prahash A, Sano M, Moravec CS, Taffet GE, et al. Telomere attrition and Chk2 activation in human heart failure. Proc Natl Acad Sci U S A 2003;100:5378–83. Oh H, Wang SC, Prahash A, Sano M, Moravec CS, Taffet GE, et al. Telomere attrition and Chk2 activation in human heart failure. Proc Natl Acad Sci U S A 2003;100:5378–83.
7.
Zurück zum Zitat Leri A, Franco S, Zacheo A, Barlucchi L, Chimenti S, Limana F, et al. Ablation of telomerase and telomere loss leads to cardiac dilatation and heart failure associated with p53 upregulation. EMBO J 2003;22:131–9. Leri A, Franco S, Zacheo A, Barlucchi L, Chimenti S, Limana F, et al. Ablation of telomerase and telomere loss leads to cardiac dilatation and heart failure associated with p53 upregulation. EMBO J 2003;22:131–9.
8.
Zurück zum Zitat van Dokkum RP, Eijkelkamp WB, Kluppel AC, Henning RH, van Goor H, Citgez M, et al. Myocardial infarction enhances progressive renal damage in an experimental model for cardio-renal interaction. J Am Soc Nephrol 2004;15:3103–10. van Dokkum RP, Eijkelkamp WB, Kluppel AC, Henning RH, van Goor H, Citgez M, et al. Myocardial infarction enhances progressive renal damage in an experimental model for cardio-renal interaction. J Am Soc Nephrol 2004;15:3103–10.
9.
Zurück zum Zitat Raij L, Azar S, Keane W. Mesangial immune injury, hypertension, and progressive glomerular damage in Dahl rats. Kidney Int 1984;26:137–43. Raij L, Azar S, Keane W. Mesangial immune injury, hypertension, and progressive glomerular damage in Dahl rats. Kidney Int 1984;26:137–43.
10.
Zurück zum Zitat Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res 2002;30:e47 Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res 2002;30:e47
11.
Zurück zum Zitat Hatori N, Havu N, Hofman-Bang C, Clyne N, Pehrsson SK. Myocardial morphology and cardiac function in rats with renal failure. Jpn Circ J 2000;64:606–10. Hatori N, Havu N, Hofman-Bang C, Clyne N, Pehrsson SK. Myocardial morphology and cardiac function in rats with renal failure. Jpn Circ J 2000;64:606–10.
12.
Zurück zum Zitat Raine AE, Seymour AM, Roberts AF, Radda GK, Ledingham JG. Impairment of cardiac function and energetics in experimental renal failure. J Clin Invest 1993;92:2934–40. Raine AE, Seymour AM, Roberts AF, Radda GK, Ledingham JG. Impairment of cardiac function and energetics in experimental renal failure. J Clin Invest 1993;92:2934–40.
13.
Zurück zum Zitat Dikow R, Kihm LP, Zeier M, Kapitza J, Tornig J, Amann K, et al. Increased infarct size in uremic rats: reduced ischemia tolerance? J Am Soc Nephrol 2004;15:1530–6. Dikow R, Kihm LP, Zeier M, Kapitza J, Tornig J, Amann K, et al. Increased infarct size in uremic rats: reduced ischemia tolerance? J Am Soc Nephrol 2004;15:1530–6.
14.
Zurück zum Zitat van der Harst P, van der Steege G, de Boer RA, Voors AA, Hall AS, Mulder MJ, et al. Telomere length of circulating leukocytes is decreased in patients with chronic heart failure. J Am Coll Cardiol 2007;49:1459–64. van der Harst P, van der Steege G, de Boer RA, Voors AA, Hall AS, Mulder MJ, et al. Telomere length of circulating leukocytes is decreased in patients with chronic heart failure. J Am Coll Cardiol 2007;49:1459–64.
15.
Zurück zum Zitat van der Harst P, Wong LS, de Boer RA, Brouilette SW, van der Steege G, Voors AA, et al. Possible association between telomere length and renal dysfunction in patients with chronic heart failure. Am J Cardiol 2008;102:207–10. van der Harst P, Wong LS, de Boer RA, Brouilette SW, van der Steege G, Voors AA, et al. Possible association between telomere length and renal dysfunction in patients with chronic heart failure. Am J Cardiol 2008;102:207–10.
16.
Zurück zum Zitat Saretzki G, Murphy MP, von Zglinicki T. MitoQ counteracts telomere shortening and elongates lifespan of fibroblasts under mild oxidative stress. Aging Cell 2003;2:141–3. Saretzki G, Murphy MP, von Zglinicki T. MitoQ counteracts telomere shortening and elongates lifespan of fibroblasts under mild oxidative stress. Aging Cell 2003;2:141–3.
17.
Zurück zum Zitat Serra V, von Zglinicki T, Lorenz M, Saretzki G. Extracellular superoxide dismutase is a major antioxidant in human fibroblasts and slows telomere shortening. J Biol Chem 2003;278:6824–30. Serra V, von Zglinicki T, Lorenz M, Saretzki G. Extracellular superoxide dismutase is a major antioxidant in human fibroblasts and slows telomere shortening. J Biol Chem 2003;278:6824–30.
18.
Zurück zum Zitat Vaziri ND, Ni Z, Oveisi F, Liang K, Pandian R. Enhanced nitric oxide inactivation and protein nitration by reactive oxygen species in renal insufficiency. Hypertension 2002;39:135–41. Vaziri ND, Ni Z, Oveisi F, Liang K, Pandian R. Enhanced nitric oxide inactivation and protein nitration by reactive oxygen species in renal insufficiency. Hypertension 2002;39:135–41.
19.
Zurück zum Zitat Oberg BP, McMenamin E, Lucas FL, McMonagle E, Morrow J, Ikizler TA, et al. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int 2004;65:1009–16. Oberg BP, McMenamin E, Lucas FL, McMonagle E, Morrow J, Ikizler TA, et al. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int 2004;65:1009–16.
20.
Zurück zum Zitat von Zglinicki T. Oxidative stress shortens telomeres. Trends Biochem Sci 2002;27:339–44. von Zglinicki T. Oxidative stress shortens telomeres. Trends Biochem Sci 2002;27:339–44.
21.
Zurück zum Zitat Cao Y, Li H, Mu FT, Ebisui O, Funder JW, Liu JP. Telomerase activation causes vascular smooth muscle cell proliferation in genetic hypertension. FASEB J 2002;16:96–8. Cao Y, Li H, Mu FT, Ebisui O, Funder JW, Liu JP. Telomerase activation causes vascular smooth muscle cell proliferation in genetic hypertension. FASEB J 2002;16:96–8.
22.
Zurück zum Zitat Ide T, Tsutsui H, Hayashidani S, Kang D, Suematsu N, Nakamura K, et al. Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res 2001;88:529–35. Ide T, Tsutsui H, Hayashidani S, Kang D, Suematsu N, Nakamura K, et al. Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res 2001;88:529–35.
23.
Zurück zum Zitat Maulik N, Yoshida T, Das DK. Oxidative stress developed during the reperfusion of ischemic myocardium induces apoptosis. Free Radic Biol Med 1998;24:869–75. Maulik N, Yoshida T, Das DK. Oxidative stress developed during the reperfusion of ischemic myocardium induces apoptosis. Free Radic Biol Med 1998;24:869–75.
24.
Zurück zum Zitat Koike MK, de Carvalho FC, de Lourdes HM. Bradykinin B2 receptor antagonism attenuates inflammation, mast cell infiltration and fibrosis in remote myocardium after infarction in rats. Clin Exp Pharmacol Physiol 2005;32:1131–6. Koike MK, de Carvalho FC, de Lourdes HM. Bradykinin B2 receptor antagonism attenuates inflammation, mast cell infiltration and fibrosis in remote myocardium after infarction in rats. Clin Exp Pharmacol Physiol 2005;32:1131–6.
25.
Zurück zum Zitat Sun Y, Zhang JQ, Zhang J, Lamparter S. Cardiac remodeling by fibrous tissue after infarction in rats. J Lab Clin Med 2000;135: 316–23. Sun Y, Zhang JQ, Zhang J, Lamparter S. Cardiac remodeling by fibrous tissue after infarction in rats. J Lab Clin Med 2000;135: 316–23.
26.
Zurück zum Zitat Dean RG, Balding LC, Candido R, Burns WC, Cao Z, Twigg SM, et al. Connective tissue growth factor and cardiac fibrosis after myocardial infarction. J Histochem Cytochem 2005;53:1245–56. Dean RG, Balding LC, Candido R, Burns WC, Cao Z, Twigg SM, et al. Connective tissue growth factor and cardiac fibrosis after myocardial infarction. J Histochem Cytochem 2005;53:1245–56.
27.
Zurück zum Zitat Wolf WC, Yoshida H, Agata J, Chao L, Chao J. Human tissue kallikrein gene delivery attenuates hypertension, renal injury, and cardiac remodeling in chronic renal failure. Kidney Int 2000;58: 730–9. Wolf WC, Yoshida H, Agata J, Chao L, Chao J. Human tissue kallikrein gene delivery attenuates hypertension, renal injury, and cardiac remodeling in chronic renal failure. Kidney Int 2000;58: 730–9.
28.
Zurück zum Zitat Nabokov AV, Amann K, Wessels S, Munter K, Wagner J, Ritz E. Endothelin receptor antagonists influence cardiovascular morphology in uremic rats. Kidney Int 1999;55:512–9. Nabokov AV, Amann K, Wessels S, Munter K, Wagner J, Ritz E. Endothelin receptor antagonists influence cardiovascular morphology in uremic rats. Kidney Int 1999;55:512–9.
29.
Zurück zum Zitat Brouilette SW, Moore JS, McMahon AD, Thompson JR, Ford I, Shepherd J, et al. Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. Lancet 2007;369:107–14. Brouilette SW, Moore JS, McMahon AD, Thompson JR, Ford I, Shepherd J, et al. Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. Lancet 2007;369:107–14.
30.
Zurück zum Zitat Kurz DJ, Kloeckener-Gruissem B, Akhmedov A, Eberli FR, Buhler I, Berger W, et al. Degenerative aortic valve stenosis, but not coronary disease, is associated with shorter telomere length in the elderly. Arterioscler Thromb Vasc Biol 2006;26:e114–e117 Kurz DJ, Kloeckener-Gruissem B, Akhmedov A, Eberli FR, Buhler I, Berger W, et al. Degenerative aortic valve stenosis, but not coronary disease, is associated with shorter telomere length in the elderly. Arterioscler Thromb Vasc Biol 2006;26:e114–e117
31.
Zurück zum Zitat Martin-Ruiz C, Saretzki G, Petrie J, Ladhoff J, Jeyapalan J, Wei W, et al. Stochastic variation in telomere shortening rate causes heterogeneity of human fibroblast replicative life span. J Biol Chem 2004; 279:17826–33. Martin-Ruiz C, Saretzki G, Petrie J, Ladhoff J, Jeyapalan J, Wei W, et al. Stochastic variation in telomere shortening rate causes heterogeneity of human fibroblast replicative life span. J Biol Chem 2004; 279:17826–33.
Metadaten
Titel
Renal failure induces telomere shortening in the rat heart
verfasst von
L. S. Wong
W. A. Windt
A. J. Roks
R. P. van Dokkum
R. G. Schoemaker
D. de Zeeuw
R. H. Henning
Publikationsdatum
01.05.2009
Verlag
Bohn Stafleu van Loghum
Erschienen in
Netherlands Heart Journal / Ausgabe 5/2009
Print ISSN: 1568-5888
Elektronische ISSN: 1876-6250
DOI
https://doi.org/10.1007/BF03086245

Weitere Artikel der Ausgabe 5/2009

Netherlands Heart Journal 5/2009 Zur Ausgabe

Screening-Mammografie offenbart erhöhtes Herz-Kreislauf-Risiko

26.04.2024 Mammografie Nachrichten

Routinemäßige Mammografien helfen, Brustkrebs frühzeitig zu erkennen. Anhand der Röntgenuntersuchung lassen sich aber auch kardiovaskuläre Risikopatientinnen identifizieren. Als zuverlässiger Anhaltspunkt gilt die Verkalkung der Brustarterien.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Adipositas-Medikament auch gegen Schlafapnoe wirksam

24.04.2024 Adipositas Nachrichten

Der als Antidiabetikum sowie zum Gewichtsmanagement zugelassene Wirkstoff Tirzepatid hat in Studien bei adipösen Patienten auch schlafbezogene Atmungsstörungen deutlich reduziert, informiert der Hersteller in einer Vorab-Meldung zum Studienausgang.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.