Sinoatrial node dysfunction and early unexpected death of mice with a defect of klotho gene expression - PubMed (original) (raw)
. 2004 Apr 13;109(14):1776-82.
doi: 10.1161/01.CIR.0000124224.48962.32. Epub 2004 Mar 22.
Toshihiko Fujimori, Yoko Kurotaki, Haruo Honjo, Hiroshi Tsujikawa, Kenji Yasui, Jong-Kook Lee, Kaichiro Kamiya, Kiyoyuki Kitaichi, Koji Yamamoto, Masafumi Ito, Takahisa Kondo, Shigeo Iino, Yasuya Inden, Makoto Hirai, Toyoaki Murohara, Itsuo Kodama, Yo-ichi Nabeshima
Affiliations
- PMID: 15037532
- DOI: 10.1161/01.CIR.0000124224.48962.32
Sinoatrial node dysfunction and early unexpected death of mice with a defect of klotho gene expression
Kyosuke Takeshita et al. Circulation. 2004.
Abstract
Background: Homozygous mutant mice with a defect of klotho gene expression (kl/kl) show multiple age-related disorders and premature death from unknown causes.
Methods and results: The kl/kl mice subjected to 20-hour restraint stress showed a high rate (20/30) of sudden death, which was associated with sinoatrial node dysfunction (conduction block or arrest). Heart rate and plasma norepinephrine of kl/kl mice, unlike those of wild-type (WT) mice, failed to increase during the stress. Intrinsic heart rate after pharmacological blockade of autonomic nerves in kl/kl mice was significantly lower than that in WT mice (380+/-33 versus 470+/-44 bpm; n=7). The sinus node recovery time after an overdrive pacing (600 bpm, 30 seconds) in kl/kl mice was significantly longer than in WT mice (392+/-37 versus 233+/-24 ms; n=6). In isolated sinoatrial node preparations, the positive chronotropic effect of isoproterenol was significantly less, whereas the negative chronotropic effect of acetylcholine was significantly greater in kl/kl than in WT mice. There was no degenerative structural change in the sinoatrial node of kl/kl mice. The precise localization of klotho was analyzed in newly prepared klotho-null mice with a reporter gene system (kl(-geo)). Homozygous kl(-geo) mice showed characteristic age-associated phenotypes that were almost identical to those of kl/kl mice. In the kl(-geo) mice, klotho expression was recognized exclusively in the sinoatrial node region in the heart in addition to parathyroid, kidney, and choroid plexus.
Conclusions: In the heart, klotho is expressed solely at the sinoatrial node. klotho gene expression is essential for the sinoatrial node to function as a dependable pacemaker under conditions of stress.
Similar articles
- Regulation of multiple ageing-like phenotypes by inducible klotho gene expression in klotho mutant mice.
Masuda H, Chikuda H, Suga T, Kawaguchi H, Kuro-o M. Masuda H, et al. Mech Ageing Dev. 2005 Dec;126(12):1274-83. doi: 10.1016/j.mad.2005.07.007. Epub 2005 Sep 6. Mech Ageing Dev. 2005. PMID: 16144705 - Improvement of multiple pathophysiological phenotypes of klotho (kl/kl) mice by adenovirus-mediated expression of the klotho gene.
Shiraki-Iida T, Iida A, Nabeshima Y, Anazawa H, Nishikawa S, Noda M, Kuro-o M, Nabeshima Y. Shiraki-Iida T, et al. J Gene Med. 2000 Jul-Aug;2(4):233-42. doi: 10.1002/1521-2254(200007/08)2:4<233::AID-JGM110>3.0.CO;2-5. J Gene Med. 2000. PMID: 10953914 - Role of force--frequency relation during AV-block, sinus node block and beta-adrenoceptor block in conscious animals.
De Pauw M, Vilaine JP, Heyndrickx GR. De Pauw M, et al. Basic Res Cardiol. 2004 Sep;99(5):360-71. doi: 10.1007/s00395-004-0481-8. Epub 2004 Jul 23. Basic Res Cardiol. 2004. PMID: 15338245 - [Physiopathology of the sinus node and sinoatrial conduction].
Guize L, Le Heuzey JY, Cabanis C, Lavergne T, Boutjdir M. Guize L, et al. Arch Mal Coeur Vaiss. 1990 Nov;83(12):1871-7. Arch Mal Coeur Vaiss. 1990. PMID: 2125200 Review. French. - [Cognition impairment in the klotho gene mutant mice and oxidative stress].
Nagai T, Yamada K, Kim HC, Noda Y, Nabeshima Y, Nabeshima T. Nagai T, et al. Nihon Shinkei Seishin Yakurigaku Zasshi. 2003 Oct;23(5):211-7. Nihon Shinkei Seishin Yakurigaku Zasshi. 2003. PMID: 14653227 Review. Japanese.
Cited by
- Gender-specific association between circulating serum Klotho and metabolic components in adults.
Wang Z, Zhang H, Zheng G, Wang Z, Shi L. Wang Z, et al. BMC Endocr Disord. 2024 Sep 27;24(1):198. doi: 10.1186/s12902-024-01737-8. BMC Endocr Disord. 2024. PMID: 39334012 Free PMC article. - Genetic determinants of blood pressure and heart rate identified through ENU-induced mutagenesis with automated meiotic mapping.
Teixeira SK, Pontes R, Zuleta LFG, Wang J, Xu D, Hildebrand S, Russell J, Zhan X, Choi M, Tang M, Li X, Ludwig S, Beutler B, Krieger JE. Teixeira SK, et al. Sci Adv. 2024 Mar;10(9):eadj9797. doi: 10.1126/sciadv.adj9797. Epub 2024 Mar 1. Sci Adv. 2024. PMID: 38427739 Free PMC article. - Soluble Klotho, a Potential Biomarker of Chronic Kidney Disease-Mineral Bone Disorders Involved in Healthy Ageing: Lights and Shadows.
Martín-Vírgala J, Martín-Carro B, Fernández-Villabrille S, Ruiz-Torres MP, Gómez-Alonso C, Rodríguez-García M, Fernández-Martín JL, Alonso-Montes C, Panizo S, Cannata-Andía JB, Naves-Díaz M, Carrillo-López N. Martín-Vírgala J, et al. Int J Mol Sci. 2024 Feb 3;25(3):1843. doi: 10.3390/ijms25031843. Int J Mol Sci. 2024. PMID: 38339121 Free PMC article. Review. - FGF23 and klotho at the intersection of kidney and cardiovascular disease.
Edmonston D, Grabner A, Wolf M. Edmonston D, et al. Nat Rev Cardiol. 2024 Jan;21(1):11-24. doi: 10.1038/s41569-023-00903-0. Epub 2023 Jul 13. Nat Rev Cardiol. 2024. PMID: 37443358 Review. - Neuroprotective Role of Klotho on Dementia.
Ananya FN, Ahammed MR, Lahori S, Parikh C, Lawrence JA, Sulachni F, Barqawi T, Kamwal C. Ananya FN, et al. Cureus. 2023 Jun 6;15(6):e40043. doi: 10.7759/cureus.40043. eCollection 2023 Jun. Cureus. 2023. PMID: 37425590 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases