Role of the kisspeptin-KISS1R axis in the pathogenesis of chronic kidney disease and uremic cardiomyopathy.
Apoptosis
Cardiac hypertrophy
Chronic renal failure
Fibrosis
Hypertension
Inflammaging
Kisspeptin-13
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
21 Nov 2023
21 Nov 2023
Historique:
received:
13
06
2023
accepted:
07
11
2023
medline:
21
11
2023
pubmed:
21
11
2023
entrez:
21
11
2023
Statut:
aheadofprint
Résumé
The prevalence of chronic kidney disease (CKD) is increasing globally, especially in elderly patients. Uremic cardiomyopathy is a common cardiovascular complication of CKD, characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and fibrosis. Kisspeptins and their receptor, KISS1R, exert a pivotal influence on kidney pathophysiology and modulate age-related pathologies across various organ systems. KISS1R agonists, including kisspeptin-13 (KP-13), hold promise as novel therapeutic agents within age-related biological processes and kidney-related disorders. Our investigation aimed to elucidate the impact of KP-13 on the trajectory of CKD and uremic cardiomyopathy. Male Wistar rats (300-350 g) were randomized into four groups: (I) sham-operated, (II) 5/6 nephrectomy-induced CKD, (III) CKD subjected to a low dose of KP-13 (intraperitoneal 13 µg/day), and (IV) CKD treated with a higher KP-13 dose (intraperitoneal 26 µg/day). Treatments were administered daily from week 3 for 10 days. After 13 weeks, KP-13 increased systemic blood pressure, accentuating diastolic dysfunction's echocardiographic indicators and intensifying CKD-associated markers such as serum urea levels, glomerular hypertrophy, and tubular dilation. Notably, KP-13 did not exacerbate circulatory uremic toxin levels, renal inflammation, or fibrosis markers. In contrast, the higher KP-13 dose correlated with reduced posterior and anterior wall thickness, coupled with diminished cardiomyocyte cross-sectional areas and concurrent elevation of inflammatory (Il6, Tnf), fibrosis (Col1), and apoptosis markers (Bax/Bcl2) relative to the CKD group. In summary, KP-13's influence on CKD and uremic cardiomyopathy encompassed heightened blood pressure and potentially activated inflammatory and apoptotic pathways in the left ventricle.
Identifiants
pubmed: 37987885
doi: 10.1007/s11357-023-01017-8
pii: 10.1007/s11357-023-01017-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Research, Development and Innovation Office
ID : NKFIH FK129094
Organisme : National Research, Development and Innovation Office
ID : EFOP-3.6.2-16-2017-00006
Organisme : National Research, Development and Innovation Office
ID : GINOP-2.3.2-15-2016-00040
Organisme : Tempus Közalapítvány
ID : Stipendium Hungaricum Scholarship
Organisme : Szent-Györgyi Albert Orvostudományi Kar, Szegedi Tudományegyetem
ID : Albert Szent-Györgyi Scholarship for PhD students
Organisme : Emberi Eroforrások Minisztériuma
ID : UNKP-20-5-SZTE-166
Organisme : Emberi Eroforrások Minisztériuma
ID : UNKP-19-3-SZTE-160
Organisme : Magyar Tudományos Akadémia
ID : Bolyai János Kutatási Ösztöndíj
Organisme : Nemzeti Kutatási, Fejlesztési és Innovaciós Alap
ID : EFOP 3.6.3-VEKOP-16-2017-00009
Organisme : Szeged Scientists Academy Program
ID : TSZ:34232-3/2016/INTFIN
Informations de copyright
© 2023. The Author(s).
Références
Elshahat S, Cockwell P, Maxwell AP, Griffin M, O’Brien T, O’Neill C. The impact of chronic kidney disease on developed countries from a health economics perspective: a systematic scoping review. PLoS ONE. 2020;15: e0230512. https://doi.org/10.1371/journal.pone.0230512 .
doi: 10.1371/journal.pone.0230512
GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395:709–33. https://doi.org/10.1016/S0140-6736(20)30045-3 .
doi: 10.1016/S0140-6736(20)30045-3
McClure M, Jorna T, Wilkinson L, Taylor J. Elderly patients with chronic kidney disease: do they really need referral to the nephrology clinic? Clin Kidney J. 2017;10:698–702. https://doi.org/10.1093/ckj/sfx034 .
doi: 10.1093/ckj/sfx034
Bolignano D, Mattace-Raso F, Sijbrands EJG, Zoccali C. The aging kidney revisited: a systematic review. Ageing Res Rev. 2014;14:65–80. https://doi.org/10.1016/j.arr.2014.02.003 .
doi: 10.1016/j.arr.2014.02.003
Csiszar A, Toth J, Peti-Peterdi J, Ungvari Z. The aging kidney: role of endothelial oxidative stress and inflammation. Acta Physiol Hung. 2007;94:107–15. https://doi.org/10.1556/APhysiol.94.2007.1-2.10 .
doi: 10.1556/APhysiol.94.2007.1-2.10
Ungvari Z, Tarantini S, Donato AJ, Galvan V, Csiszar A. Mechanisms of vascular aging. Circ Res. 2018;123:849–67. https://doi.org/10.1161/CIRCRESAHA.118.311378 .
doi: 10.1161/CIRCRESAHA.118.311378
Vlassara H, Torreggiani M, Post JB, Zheng F, Uribarri J, Striker GE. Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging. Kidney Int Suppl. 2009;76:S3-11. https://doi.org/10.1038/ki.2009.401 .
doi: 10.1038/ki.2009.401
Wang X, Shapiro JI. Evolving concepts in the pathogenesis of uraemic cardiomyopathy. Nat Rev Nephrol. 2019;15:159–75. https://doi.org/10.1038/s41581-018-0101-8 .
doi: 10.1038/s41581-018-0101-8
Duni A, Liakopoulos V, Rapsomanikis K-P, Dounousi E. Chronic kidney disease and disproportionally increased cardiovascular damage: does oxidative stress explain the burden? Oxid Med Cell Longev. 2017;2017:9036450. https://doi.org/10.1155/2017/9036450 .
doi: 10.1155/2017/9036450
Husain-Syed F, McCullough PA, Birk H-W, Renker M, Brocca A, Seeger W, Ronco C. Cardio-pulmonary-renal interactions: a multidisciplinary approach. J Am Coll Cardiol. 2015;65:2433–48. https://doi.org/10.1016/j.jacc.2015.04.024 .
doi: 10.1016/j.jacc.2015.04.024
Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Cardiorenal syndrome. J Am Coll Cardiol. 2008;52:1527–39. https://doi.org/10.1016/j.jacc.2008.07.051 .
doi: 10.1016/j.jacc.2008.07.051
Kaesler N, Babler A, Floege J, Kramann R. Cardiac remodeling in chronic kidney disease. Toxins (Basel). 2020. https://doi.org/10.3390/toxins12030161 .
doi: 10.3390/toxins12030161
Sárközy M, Kovács ZZA, Kovács MG, Gáspár R, Szűcs G, Dux L. Mechanisms and modulation of oxidative/nitrative stress in type 4 cardio-renal syndrome and renal sarcopenia. Front Physiol. 2018;9:1648. https://doi.org/10.3389/fphys.2018.01648 .
doi: 10.3389/fphys.2018.01648
Shoji I, Hirose T, Mori N, Hiraishi K, Kato I, Shibasaki A, et al. Expression of kisspeptins and kisspeptin receptor in the kidney of chronic renal failure rats. Peptides. 2010;31:1920–5. https://doi.org/10.1016/j.peptides.2010.07.001 .
doi: 10.1016/j.peptides.2010.07.001
Kim K, Choe HK. Role of hypothalamus in aging and its underlying cellular mechanisms. Mech Ageing Dev. 2019;177:74–9. https://doi.org/10.1016/j.mad.2018.04.008 .
doi: 10.1016/j.mad.2018.04.008
Hrabovszky E, Takács S, Göcz B, Skrapits K. New perspectives for anatomical and molecular studies of kisspeptin neurons in the aging human brain. Neuroendocrinology. 2019;109:230–41. https://doi.org/10.1159/000496566 .
doi: 10.1159/000496566
Fang P, She Y, Zhao J, Yan J, Yu X, Jin Y, et al. Emerging roles of kisspeptin/galanin in age-related metabolic disease. Mech Ageing Dev. 2021;199: 111571. https://doi.org/10.1016/j.mad.2021.111571 .
doi: 10.1016/j.mad.2021.111571
Clarke SA, Dhillo WS. Kisspeptin across the human lifespan: evidence from animal studies and beyond. J Endocrinol. 2016;229:R83-98. https://doi.org/10.1530/JOE-15-0538 .
doi: 10.1530/JOE-15-0538
Barabás K, Szabó-Meleg E, Ábrahám IM. Effect of inflammation on female gonadotropin-releasing hormone (GnRH) neurons: mechanisms and consequences. Int J Mol Sci. 2020. https://doi.org/10.3390/ijms21020529 .
doi: 10.3390/ijms21020529
Watanabe T, Sato K. Roles of the kisspeptin/GPR54 system in pathomechanisms of atherosclerosis. Nutr Metab Cardiovasc Dis. 2020;30:889–95. https://doi.org/10.1016/j.numecd.2020.02.017 .
doi: 10.1016/j.numecd.2020.02.017
Guzman S, Brackstone M, Wondisford F, Babwah AV, Bhattacharya M. KISS1/KISS1R and breast cancer: metastasis promoter. Semin Reprod Med. 2019;37:197–206. https://doi.org/10.1055/s-0039-3400968 .
doi: 10.1055/s-0039-3400968
Ly T, Harihar S, Welch DR. KISS1 in metastatic cancer research and treatment: potential and paradoxes. Cancer Metastasis Rev. 2020;39:739–54. https://doi.org/10.1007/s10555-020-09868-9 .
doi: 10.1007/s10555-020-09868-9
Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001;276:34631–6. https://doi.org/10.1074/jbc.M104847200 .
doi: 10.1074/jbc.M104847200
Ciaramella V, Della Corte CM, Ciardiello F, Morgillo F. Kisspeptin and cancer: molecular interaction, biological functions, and future perspectives. Front Endocrinol (Lausanne). 2018;9:115. https://doi.org/10.3389/fendo.2018.00115 .
doi: 10.3389/fendo.2018.00115
Sitticharoon C, Raksadawan Y, Boonpuan P, Keadkraichaiwat I, Sririwichitchai R, Maikaew P. Serum kisspeptin is higher in hypertensive than non-hypertensive female subjects and positively correlated with systolic blood pressure. Minerva Endocrinol (Torino) 2023. https://doi.org/10.23736/S2724-6507.22.03766-6 .
Ten S-C, Gu S-Y, Niu Y-F, An X-F, Yan M, He M. Central administration of kisspeptin-10 inhibits water and sodium excretion of anesthetized male rats and the involvement of arginine vasopressin. Endocr Res. 2010;35:128–36. https://doi.org/10.3109/07435801003769995 .
doi: 10.3109/07435801003769995
Han X, Yan M, An X-F, He M, Yu J. Central administration of kisspeptin-10 inhibits natriuresis and diuresis induced by blood volume expansion in anesthetized male rats. Acta Pharmacol Sin. 2010;31:145–9. https://doi.org/10.1038/aps.2009.179 .
doi: 10.1038/aps.2009.179
Dinh H, Kovács ZZA, Márványkövi F, Kis M, Kupecz K, Szűcs G, et al. The kisspeptin-1 receptor antagonist peptide-234 aggravates uremic cardiomyopathy in a rat model. Sci Rep. 2023. https://doi.org/10.1038/s41598-023-41037-0 .
doi: 10.1038/s41598-023-41037-0
Guzman S, Dragan M, Kwon H, de Oliveira V, Rao S, Bhatt V, et al. Targeting hepatic kisspeptin receptor ameliorates nonalcoholic fatty liver disease in a mouse model. J Clin Invest. 2022. https://doi.org/10.1172/JCI145889 .
doi: 10.1172/JCI145889
Lei Z, Bai X, Ma J, Yu Q. Kisspeptin-13 inhibits bleomycin-induced pulmonary fibrosis through GPR54 in mice. Mol Med Rep. 2019;20:1049–56. https://doi.org/10.3892/mmr.2019.10341 .
doi: 10.3892/mmr.2019.10341
Mead EJ, Maguire JJ, Kuc RE, Davenport AP. Kisspeptins are novel potent vasoconstrictors in humans, with a discrete localization of their receptor, G protein-coupled receptor 54, to atherosclerosis-prone vessels. Endocrinology. 2007;148:140–7. https://doi.org/10.1210/en.2006-0818 .
doi: 10.1210/en.2006-0818
Zhang Y, Hou Y, Wang X, Ping J, Ma Z, Suo C, et al. The effects of kisspeptin-10 on serum metabolism and myocardium in rats. PLoS ONE. 2017;12: e0179164. https://doi.org/10.1371/journal.pone.0179164 .
doi: 10.1371/journal.pone.0179164
Silvestre RA, Egido EM, Hernández R, Marco J. Kisspeptin-13 inhibits insulin secretion without affecting glucagon or somatostatin release: study in the perfused rat pancreas. J Endocrinol. 2008;196:283–90. https://doi.org/10.1677/JOE-07-0454 .
doi: 10.1677/JOE-07-0454
Sárközy M, Watzinger S, Kovács ZZ, Acar E, Márványkövi F, Szűcs G, et al. Neuregulin-1β improves uremic cardiomyopathy and renal dysfunction in rats. JACC: Basic Transl Sci 2023. https://doi.org/10.1016/j.jacbts.2023.03.003 .
Hamza O, Kiss A, Kramer A-M, Trojanek S, Abraham D, Acar E, et al. Tenascin C promotes valvular remodeling in two large animal models of ischemic mitral regurgitation. Basic Res Cardiol. 2020;115:76. https://doi.org/10.1007/s00395-020-00837-5 .
doi: 10.1007/s00395-020-00837-5
Kovács ZZA, Szűcs G, Freiwan M, Kovács MG, Márványkövi FM, Dinh H, et al. Comparison of the antiremodeling effects of losartan and mirabegron in a rat model of uremic cardiomyopathy. Sci Rep. 2021;11:17495. https://doi.org/10.1038/s41598-021-96815-5 .
doi: 10.1038/s41598-021-96815-5
Sárközy M, Márványkövi FM, Szűcs G, Kovács ZZA, Szabó MR, Gáspár R, et al. Ischemic preconditioning protects the heart against ischemia-reperfusion injury in chronic kidney disease in both males and females. Biol Sex Differ. 2021;12:49. https://doi.org/10.1186/s13293-021-00392-1 .
doi: 10.1186/s13293-021-00392-1
Zacchigna S, Paldino A, Falcão-Pires I, Daskalopoulos EP, Dal Ferro M, Vodret S, et al. Towards standardization of echocardiography for the evaluation of left ventricular function in adult rodents: a position paper of the ESC Working Group on Myocardial Function. Cardiovasc Res. 2021;117:43–59. https://doi.org/10.1093/cvr/cvaa110 .
doi: 10.1093/cvr/cvaa110
Sárközy M, Gáspár R, Zvara Á, Siska A, Kővári B, Szűcs G, et al. Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212. Sci Rep. 2019;9:1302. https://doi.org/10.1038/s41598-018-37690-5 .
doi: 10.1038/s41598-018-37690-5
Kocsis GF, Sárközy M, Bencsik P, Pipicz M, Varga ZV, Pálóczi J, et al. Preconditioning protects the heart in a prolonged uremic condition. Am J Physiol Heart Circ Physiol. 2012;303:H1229–36. https://doi.org/10.1152/ajpheart.00379.2012 .
doi: 10.1152/ajpheart.00379.2012
Galla Z, Rajda C, Rácz G, Grecsó N, Baráth Á, Vécsei L, et al. Simultaneous determination of 30 neurologically and metabolically important molecules: a sensitive and selective way to measure tyrosine and tryptophan pathway metabolites and other biomarkers in human serum and cerebrospinal fluid. J Chromatogr A. 2021;1635: 461775. https://doi.org/10.1016/j.chroma.2020.461775 .
doi: 10.1016/j.chroma.2020.461775
Galla Z, Rácz G, Grecsó N, Baráth Á, Kósa M, Bereczki C, Monostori P. Improved LC-MS/MS method for the determination of 42 neurologically and metabolically important molecules in urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2021;1179: 122846. https://doi.org/10.1016/j.jchromb.2021.122846 .
doi: 10.1016/j.jchromb.2021.122846
Kovács MG, Kovács ZZA, Varga Z, Szűcs G, Freiwan M, Farkas K, et al. Investigation of the antihypertrophic and antifibrotic effects of losartan in a rat model of radiation-induced heart disease. Int J Mol Sci. 2021. https://doi.org/10.3390/ijms222312963 .
doi: 10.3390/ijms222312963
Freiwan M, Kovács MG, Kovács ZZA, Szűcs G, Dinh H, Losonczi R, et al. Investigation of the Antiremodeling effects of losartan, mirabegron and their combination on the development of doxorubicin-induced chronic cardiotoxicity in a rat model. Int J Mol Sci. 2022. https://doi.org/10.3390/ijms23042201 .
doi: 10.3390/ijms23042201
Szabó PL, Ebner J, Koenig X, Hamza O, Watzinger S, Trojanek S, et al. Cardiovascular phenotype of the Dmdmdx rat - a suitable animal model for Duchenne muscular dystrophy. Dis Model Mech. 2021. https://doi.org/10.1242/dmm.047704 .
doi: 10.1242/dmm.047704
Thum T, Galuppo P, Wolf C, Fiedler J, Kneitz S, van Laake LW, et al. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation. 2007;116:258–67. https://doi.org/10.1161/CIRCULATIONAHA.107.687947 .
doi: 10.1161/CIRCULATIONAHA.107.687947
Falconi CA, Da Junho CVC, Fogaça-Ruiz F, Vernier ICS, Da Cunha RS, Stinghen AEM, Carneiro-Ramos MS. Uremic toxins: an alarming danger concerning the cardiovascular system. Front Physiol. 2021;12: 686249. https://doi.org/10.3389/fphys.2021.686249 .
doi: 10.3389/fphys.2021.686249
Lekawanvijit S, Kompa AR, Krum H. Protein-bound uremic toxins: a long overlooked culprit in cardiorenal syndrome. Am J Physiol Renal Physiol. 2016;311:F52-62. https://doi.org/10.1152/ajprenal.00348.2015 .
doi: 10.1152/ajprenal.00348.2015
Kasama S, Furuya M, Toyama T, Ichikawa S, Kurabayashi M. Effect of atrial natriuretic peptide on left ventricular remodelling in patients with acute myocardial infarction. Eur Heart J. 2008;29:1485–94. https://doi.org/10.1093/eurheartj/ehn206 .
doi: 10.1093/eurheartj/ehn206
Wahab F, Atika B, Shahab M, Behr R. Kisspeptin signalling in the physiology and pathophysiology of the urogenital system. Nat Rev Urol. 2016;13:21–32. https://doi.org/10.1038/nrurol.2015.277 .
doi: 10.1038/nrurol.2015.277
de Albuquerque Suassuna PG, Sanders-Pinheiro H, de Paula RB. Uremic cardiomyopathy: a new piece in the chronic kidney disease-mineral and bone disorder puzzle. Front Med (Lausanne). 2018;5:206. https://doi.org/10.3389/fmed.2018.00206 .
doi: 10.3389/fmed.2018.00206
Tao H, Xu W, Qu W, Gao H, Zhang J, Cheng X, et al. Loss of ten-eleven translocation 2 induces cardiac hypertrophy and fibrosis through modulating ERK signaling pathway. Hum Mol Genet. 2021;30:865–79. https://doi.org/10.1093/hmg/ddab046 .
doi: 10.1093/hmg/ddab046
Oldfield CJ, Duhamel TA, Dhalla NS. Mechanisms for the transition from physiological to pathological cardiac hypertrophy. Can J Physiol Pharmacol. 2020;98:74–84. https://doi.org/10.1139/cjpp-2019-0566 .
doi: 10.1139/cjpp-2019-0566
Abbara A, Ratnasabapathy R, Jayasena CN, Dhillo WS. The effects of kisspeptin on gonadotropin release in non-human mammals. Adv Exp Med Biol. 2013;784:63–87. https://doi.org/10.1007/978-1-4614-6199-9_4 .
doi: 10.1007/978-1-4614-6199-9_4
Tsoutsouki J, Abbara A, Dhillo W. Novel therapeutic avenues for kisspeptin. Curr Opin Pharmacol. 2022;67: 102319. https://doi.org/10.1016/j.coph.2022.102319 .
doi: 10.1016/j.coph.2022.102319
Bond J-AP de, Tolson KP, Nasamran C, Kauffman AS, Smith JT. Unaltered hypothalamic metabolic gene expression in Kiss1r knockout mice despite obesity and reduced energy expenditure. J Neuroendocrinol 2016. https://doi.org/10.1111/jne.12430 .
Izzi-Engbeaya C, Hill TG, Bowe JE. Kisspeptin and glucose homeostasis. Semin Reprod Med. 2019;37:141–6. https://doi.org/10.1055/s-0039-3400242 .
doi: 10.1055/s-0039-3400242
Clementi A, Virzì GM, Goh CY, Cruz DN, Granata A, Vescovo G, Ronco C. Cardiorenal syndrome type 4: a review. Cardiorenal Med. 2013;3:63–70. https://doi.org/10.1159/000350397 .
doi: 10.1159/000350397
Da Pinheiro Silva AL, Da Vaz Silva MJ. Type 4 cardiorenal syndrome. Rev Port Cardiol. 2016;35:601–16. https://doi.org/10.1016/j.repc.2016.06.007 .
doi: 10.1016/j.repc.2016.06.007
Yi T, Tan K, Cho S-G, Wang Y, Luo J, Zhang W, et al. Regulation of embryonic kidney branching morphogenesis and glomerular development by KISS1 receptor (Gpr54) through NFAT2- and Sp1-mediated Bmp7 expression. J Biol Chem. 2010;285:17811–20. https://doi.org/10.1074/jbc.M110.130740 .
doi: 10.1074/jbc.M110.130740
Luedde M, Spehlmann ME, Hippe H-J, Loosen SH, Roy S, Vargas Cardenas D, et al. Serum levels of kisspeptin are elevated in critically ill patients. PLoS ONE. 2018;13: e0206064. https://doi.org/10.1371/journal.pone.0206064 .
doi: 10.1371/journal.pone.0206064
Hewitson TD, Holt SG, Smith ER. Animal models to study links between cardiovascular disease and renal failure and their relevance to human pathology. Front Immunol. 2015;6:465. https://doi.org/10.3389/fimmu.2015.00465 .
doi: 10.3389/fimmu.2015.00465
Griffin KA, Picken MM, Churchill M, Churchill P, Bidani AK. Functional and structural correlates of glomerulosclerosis after renal mass reduction in the rat. J Am Soc Nephrol. 2000;11:497–506. https://doi.org/10.1681/ASN.V113497 .
doi: 10.1681/ASN.V113497
Adam RJ, Williams AC, Kriegel AJ. Comparison of the surgical resection and infarct 5/6 nephrectomy rat models of chronic kidney disease. Am J Physiol Renal Physiol. 2022;322:F639–54. https://doi.org/10.1152/ajprenal.00398.2021 .
doi: 10.1152/ajprenal.00398.2021
Mitani S, Yabuki A, Sawa M, Chang H-S, Yamato O. Intrarenal distributions and changes of angiotensin-converting enzyme and angiotensin-converting enzyme 2 in feline and canine chronic kidney disease. J Vet Med Sci. 2014;76:45–50. https://doi.org/10.1292/jvms.13-0314 .
doi: 10.1292/jvms.13-0314
Franco V, Chen Y-F, Oparil S, Feng J an, Wang D, Hage F, Perry G. Atrial natriuretic peptide dose-dependently inhibits pressure overload-induced cardiac remodeling. Hypertension. 2004;44:746–50. https://doi.org/10.1161/01.HYP.0000144801.09557.4c .
doi: 10.1161/01.HYP.0000144801.09557.4c
Sarzani R, Allevi M, Di Pentima C, Schiavi P, Spannella F, Giulietti F. Role of cardiac natriuretic peptides in heart structure and function. Int J Mol Sci. 2022. https://doi.org/10.3390/ijms232214415 .
doi: 10.3390/ijms232214415
Saadat S, Noureddini M, Mahjoubin-Tehran M, Nazemi S, Shojaie L, Aschner M, et al. Pivotal role of TGF-β/Smad signaling in cardiac fibrosis: non-coding RNAs as effectual players. Front Cardiovasc Med. 2020;7: 588347. https://doi.org/10.3389/fcvm.2020.588347 .
doi: 10.3389/fcvm.2020.588347
Oakley AE, Clifton DK, Steiner RA. Kisspeptin signaling in the brain. Endocr Rev. 2009;30:713–43. https://doi.org/10.1210/er.2009-0005 .
doi: 10.1210/er.2009-0005
Xie Q, Kang Y, Zhang C, Xie Y, Wang C, Liu J, et al. The role of kisspeptin in the control of the hypothalamic-pituitary-gonadal axis and reproduction. Front Endocrinol (Lausanne). 2022;13: 925206. https://doi.org/10.3389/fendo.2022.925206 .
doi: 10.3389/fendo.2022.925206
Zhu N, Zhao M, Song Y, Ding L, Ni Y. The KiSS-1/GPR54 system: essential roles in physiological homeostasis and cancer biology. Genes Dis. 2022;9:28–40. https://doi.org/10.1016/j.gendis.2020.07.008 .
doi: 10.1016/j.gendis.2020.07.008
Navarro VM. Metabolic regulation of kisspeptin - the link between energy balance and reproduction. Nat Rev Endocrinol. 2020;16:407–20. https://doi.org/10.1038/s41574-020-0363-7 .
doi: 10.1038/s41574-020-0363-7
Jayasena CN, Abbara A, Comninos AN, Nijher GMK, Christopoulos G, Narayanaswamy S, et al. Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization. J Clin Invest. 2014;124:3667–77. https://doi.org/10.1172/JCI75730 .
doi: 10.1172/JCI75730
Hrabovszky E, Molnár CS, Sipos MT, Vida B, Ciofi P, Borsay BA, et al. Sexual dimorphism of kisspeptin and neurokinin B immunoreactive neurons in the infundibular nucleus of aged men and women. Front Endocrinol (Lausanne). 2011;2:80. https://doi.org/10.3389/fendo.2011.00080 .
doi: 10.3389/fendo.2011.00080
Akdag T, Uca AU, Altas M, Odabas FO, Aktas F. Level of kisspeptin-10 in patients with multiple sclerosis and the association between third ventricle diameter size and vitamin D level. Physiol Int. 2021. https://doi.org/10.1556/2060.2021.00179 .
doi: 10.1556/2060.2021.00179
Lee K-E, Jeong S, Yun SK, Kyung S, Sophie A, Moh SH, et al. Synthesis of kisspeptin-mimicking fragments and investigation of their skin anti-aging effects. Int J Mol Sci. 2020. https://doi.org/10.3390/ijms21228439 .
doi: 10.3390/ijms21228439
Mattam U, Talari NK, Paripati AK, Krishnamoorthy T, Sepuri NBV. Kisspeptin preserves mitochondrial function by inducing mitophagy and autophagy in aging rat brain hippocampus and human neuronal cell line. Biochim Biophys Acta Mol Cell Res. 2021;1868: 118852. https://doi.org/10.1016/j.bbamcr.2020.118852 .
doi: 10.1016/j.bbamcr.2020.118852
Mattam U, Talari NK, Thiriveedi VR, Fareed M, Velmurugan S, Mahadev K, Sepuri NBV. Aging reduces kisspeptin receptor (GPR54) expression levels in the hypothalamus and extra-hypothalamic brain regions. Exp Ther Med. 2021;22:1019. https://doi.org/10.3892/etm.2021.10451 .
doi: 10.3892/etm.2021.10451
Erel CT, Ozcivit IB, Inan D, Mut A, Karakus Hatipoglu B, Konukoglu D. Serum kisspeptin levels along reproductive period in women: is it a marker for aging? Gynecol Endocrinol. 2022;38:267–72. https://doi.org/10.1080/09513590.2022.2028768 .
doi: 10.1080/09513590.2022.2028768
Yan L, Nong X, Deng J, Yang G. Testosterone protects cardiomyocytes against hydrogen peroxide-induced aging by upregulating IGF1 and SIRT1 pathways. Physiol Int. 2022. https://doi.org/10.1556/2060.2022.00191 .
doi: 10.1556/2060.2022.00191
Usui S, Iso Y, Sasai M, Mizukami T, Mori H, Watanabe T, et al. Kisspeptin-10 induces endothelial cellular senescence and impaired endothelial cell growth. Clin Sci (Lond). 2014;127:47–55. https://doi.org/10.1042/CS20130505 .
doi: 10.1042/CS20130505
Huang C, Wang H-Y, Wang M-E, Hsu M-C, Wu Y-HS, Jiang Y-F, et al. Kisspeptin-activated autophagy independently suppresses non-glucose-stimulated insulin secretion from pancreatic β-cells. Sci Rep. 2019;9:17451. https://doi.org/10.1038/s41598-019-53826-7 .
doi: 10.1038/s41598-019-53826-7
Khonacha SE, Mirbehbahani SH, Rahdar M, Davoudi S, Borjkhani M, Khodagholi F, et al. Kisspeptin-13 prevented the electrophysiological alterations induced by amyloid-beta pathology in rat: possible involvement of stromal interaction molecules and pCREB. Brain Res Bull. 2022;184:13–23. https://doi.org/10.1016/j.brainresbull.2022.03.003 .
doi: 10.1016/j.brainresbull.2022.03.003
Milton NGN, Chilumuri A, Rocha-Ferreira E, Nercessian AN, Ashioti M. Kisspeptin prevention of amyloid-β peptide neurotoxicity in vitro. ACS Chem Neurosci. 2012;3:706–19. https://doi.org/10.1021/cn300045d .
doi: 10.1021/cn300045d
Hou Y, Wang X, Ping J, Lei Z, Gao Y, Ma Z, et al. Metabonomics approach to assessing the modulatory effects of kisspeptin-10 on liver injury induced by heat stress in Rats. Sci Rep. 2017;7:7020. https://doi.org/10.1038/s41598-017-06017-1 .
doi: 10.1038/s41598-017-06017-1
Huang Y, Guo Y, Huang L, Fang Y, Li D, Liu R, et al. Kisspeptin-54 attenuates oxidative stress and neuronal apoptosis in early brain injury after subarachnoid hemorrhage in rats via GPR54/ARRB2/AKT/GSK3β signaling pathway. Free Radic Biol Med. 2021;171:99–111. https://doi.org/10.1016/j.freeradbiomed.2021.05.012 .
doi: 10.1016/j.freeradbiomed.2021.05.012