{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T19:40:29Z","timestamp":1785267629385,"version":"3.55.0"},"reference-count":43,"publisher":"IMR Press","issue":"6","license":[{"start":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: Although the mesenteric artery plays a key role in regulating peripheral blood pressure, the molecular mechanisms that underlie the development of essential hypertension are not yet fully understood. Materials and Methods: We explored candidate genes for hypertension using three related strains of spontaneously hypertensive rats (SHRs) that mimic human essential hypertension. In this study we used DNA microarrays, a powerful tool for studying genetic diseases, to compare gene expression in the mesenteric artery of three SHR substrains: SHR, stroke-prone SHR (SHRSP), and malignant SHRSP (M-SHRSP). Results: Compared to normotensive 6-week old Wistar Kyoto rats (WKY), higher blood pressure correlated with overexpression of 31 genes and with down regulation of 24 genes. Adam23, which negatively regulates potassium current, and the potassium channel genes, Kcnc2 and Kcnq5, were associated with the onset of hypertension. In addition, Spock2 and Agtrap were identified as strengtheners of hypertension by analyzing up and down regulated genes at 9-weeks of age. Conclusions: Adam23, Kcnc2 and Kcnq5 appear to be factors for the onset of hypertension, while Spock2 and Agtrap are as factors that strengthen hypertension. These findings contribute to our understanding of the pathophysiology of hypertension and to the development of treatment for this condition.<\/jats:p>","DOI":"10.31083\/j.fbl2706191","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T01:01:51Z","timestamp":1655427711000},"source":"Crossref","is-referenced-by-count":15,"title":["Hypertension-Associated Genes in the Mesenteric Artery of Three Spontaneously Hypertensive Rat Substrains Identified Using a DNA Array Method"],"prefix":"10.31083","volume":"27","author":[{"given":"Yoshinori","family":"Aragane","sequence":"first","affiliation":[{"name":"Tougenkai Dermatology, Osaka-city, 540-8511 Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Higashino","sequence":"first","affiliation":[{"name":"Department of Dermatology, Self-Defense Forces Central Hospital, Setagaya-ward, 154-8532 Tokyo, Japan"},{"name":"Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ward, 113-0033 Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosho","family":"Kinoshita","sequence":"first","affiliation":[{"name":"Kosho Clinic, Nishinomiya-city, 662-0051 Hyogo, Japan"},{"name":"Department of Pharmacology, Kindai University School of Medicine, Osaka-Sayama-city, 589-8511 Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Said","family":"Ashenagar","sequence":"first","affiliation":[{"name":"Department of Social and Environmental Medicine, Faculty of Medicine, Saga University, Saga-city, 849-8501 Saga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Higashino","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Kindai University School of Medicine, Osaka-Sayama-city, 589-8511 Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2022,6,15]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Yan J, Zhou J, Huang J, Zhang H, Deng Z, Du Y. The outcomes of acute myocardial infarction patients comorbidity with hypertension and hyperhomocysteinemia. Scientific Reports. 2021; 11: 22936.","DOI":"10.1038\/s41598-021-02340-w"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Ruiz-Ortega M, Rayego-Mateos S, Lamas S, Ortiz A, Rodrigues-Diez RR. Targeting the progression of chronic kidney disease. Nature Reviews Nephrology. 2020; 16: 269\u2013288.","DOI":"10.1038\/s41581-019-0248-y"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Alloubani A, Saleh A, Abdelhafiz I. Hypertension and diabetes mellitus as predictive risk factors for stroke. Diabetes & Metabolic Syndrome. 2018; 12: 577\u2013584.","DOI":"10.1016\/j.dsx.2018.03.009"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Hisamatsu T, Segawa H, Kadota A, Ohkubo T, Arima H, Miura K. Epidemiology of hypertension in Japan: beyond the new 2019 Japanese guidelines. Hypertension Research. 2020; 43: 1344\u20131351.","DOI":"10.1038\/s41440-020-0508-z"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Hisamatsu T, Miura K. Epidemiology and control of hypertension in Japan: a comparison with Western countries. Journal of Human Hypertension. 2021. (in press)","DOI":"10.1038\/s41371-021-00534-3"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Kelly TN, Takeuchi F, Tabara Y, Edwards TL, Kim YJ, Chen P, et al. Genome-Wide Association Study Meta-Analysis Reveals Transethnic Replication of Mean Arterial and Pulse Pressure Loci. Hypertension. 2013; 62: 853\u2013859.","DOI":"10.1161\/HYPERTENSIONAHA.113.01148"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Okamoto K, Aoki K. Development of a strain of spontaneously hypertensive rat. Japanese Circulation Journal. 1963; 27: 282\u2013293.","DOI":"10.1253\/jcj.27.282"},{"key":"ref8","unstructured":"Okamoto K, Yamori Y, Nagaoka A. Establishment of the stroke-prone spontaneously hypertensive rats (SHR). Circulation Research. 1974; 34: 143\u2013153."},{"key":"ref9","unstructured":"Okamoto K, Yamamoto K, Morita N, Ohta Y. Establishment and characteristics of rat with precocious and severe hypertension (M-SHRSP). Acta medica Kinki University. 1985; 10: 73\u201395."},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Drmanac R, Drmanac S, Strezoska Z, Paunesku T, Labat I, Zeremski M, et al. DNA Sequence Determination by Hybridization: a Strategy for Efficient Large-Scale Sequencing. Science. 1993; 260: 1649\u20131652.","DOI":"10.1126\/science.8503011"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Schena M. Microarrays: biotechnology\u2019s discovery platform for functional genomics. Trends in Biotechnology. 1998; 16: 301\u2013306.","DOI":"10.1016\/S0167-7799(98)01219-0"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Hacia JG, Brody LC, Collins FS. Applications of DNA chips for genomic analysis. Molecular Psychiatry. 1998; 3: 483\u2013492.","DOI":"10.1038\/sj.mp.4000475"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Higashino. Gene expression in the adrenal glands of three spontaneously hypertensive rat substrains. Molecular Medicine Reports. 2010; 3: 213\u2013222.","DOI":"10.3892\/mmr_000000242"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Kinoshita K, Ashenagar MS, Tabuchi M, Higashino H. Whole rat DNA array survey for candidate genes related to hypertension in kidneys from three spontaneously hypertensive rat substrains at two stages of age and with hypotensive induction caused by hydralazine hydrochloride. Experimental and Therapeutic Medicine. 2011; 2: 201\u2013212.","DOI":"10.3892\/etm.2011.193"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Ikawa T, Watanabe Y, Okuzaki D, Goto N, Okamura N, Yamanishi K, et al. A new approach to identifying hypertension-associated genes in the mesenteric artery of spontaneously hypertensive rats and stroke-prone spontaneously hypertensive rats. Journal of Hypertension. 2019; 37: 1644\u20131656.","DOI":"10.1097\/HJH.0000000000002083"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Surendran P, Drenos F, Young R, Warren H, Cook JP, Manning AK, et al. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. Nature Genetics. 2016; 48: 1151\u20131161.","DOI":"10.1038\/ng.3654"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Costantino S, Paneni F, Cosentino F. Ageing, metabolism and cardiovascular disease. The Journal of Physiology. 2016; 594: 2061\u20132073.","DOI":"10.1113\/JP270538"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Xu X, Zhao Y, Simon R. Gene Set Expression Comparison kit for BRB-ArrayTools. Bioinformatics. 2008; 24: 137\u2013139.","DOI":"10.1093\/bioinformatics\/btm541"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Borthong J, Omori R, Sugimoto C, Suthienkul O, Nakao R, Ito K. Comparison of Database Search Methods for the Detection of Legionella pneumophila in Water Samples Using Metagenomic Analysis. Frontiers in Microbiology. 2018; 9: 1272.","DOI":"10.3389\/fmicb.2018.01272"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Yang Y, Ding L, Li Y, Xuan C. Hsa_circ_0039411 promotes tumorigenesis and progression of papillary thyroid cancer by miR-1179\/ABCA9 and miR-1205\/MTA1 signaling pathways. Journal of Cellular Physiology. 2020; 235: 1321\u20131329.","DOI":"10.1002\/jcp.29048"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Markus-Koch A, Schmitt O, Seemann S, Lukas J, Koczan D, Ernst M, et al. ADAM23 promotes neuronal differentiation of human neural progenitor cells. Cellular & Molecular Biology Letters. 2017; 22: 16.","DOI":"10.1186\/s11658-017-0045-1"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Ota M, Mochizuki S, Shimoda M, Abe H, Miyamae Y, Ishii K, et al. ADAM23 is downregulated in side population and suppresses lung metastasis of lung carcinoma cells. Cancer Science. 2016; 107: 433\u2013443.","DOI":"10.1111\/cas.12895"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Lancaster E, Burnor E, Zhang J, Lancaster E. ADAM23 is a negative regulator of Kv1.1\/Kv1.4 potassium currents. Neuroscience Letters. 2019; 704: 159\u2013163.","DOI":"10.1016\/j.neulet.2019.04.012"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Hasan R, Jaggar JH. Kv channel trafficking and control of vascular tone. Microcirculation. 2018; 25: 10.","DOI":"10.1111\/micc.12418"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Beato M, Sharma P. Peptidyl arginine deiminase 2 (PADI2)-mediated arginine citrullination modulates transcription in cancer. International Journal of Molecular Sciences. 2020; 21: 1351.","DOI":"10.3390\/ijms21041351"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Michetti F, D\u2019Ambrosi N, Toesca A, Puglisi MA, Serrano A, Marchese E, et al. The S100B story: from biomarker to active factor in neural injury. Journal of Neurochemistry. 2019; 148: 168\u2013187.","DOI":"10.1111\/jnc.14574"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Kim S, Kwon S, Kam T, Panicker N, Karuppagounder SS, Lee S, et al. Transneuronal Propagation of Pathologic \u03b1-Synuclein from the Gut to the Brain Models Parkinson\u2019s Disease. Neuron. 2019; 103: 627\u2013641.e7.","DOI":"10.1016\/j.neuron.2019.05.035"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Rasmussen MK, Mestre H, Nedergaard M. The glymphatic pathway in neurological disorders. The Lancet Neurology. 2018; 17: 1016\u20131024.","DOI":"10.1016\/S1474-4422(18)30318-1"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Jin B, Zhang H, Binder DK, Verkman AS. Aquaporin-4\u2013dependent K+ and water transport modeled in brain extracellular space following neuroexcitation. Journal of General Physiology. 2013; 141: 119\u2013132.","DOI":"10.1085\/jgp.201210883"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Hsu H, Duning K, Meyer HH, St\u00f6lting M, Weide T, Kreusser S, et al. Hypertension in mice lacking the CXCR3 chemokine receptor. American Journal of Physiology-Renal Physiology. 2009; 296: F780\u2013F789.","DOI":"10.1152\/ajprenal.90444.2008"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Tripathi N, Paliwal S, Sharma S, Verma K, Gururani R, Tiwari A, et al. Discovery of Novel Soluble Epoxide Hydrolase Inhibitors as Potent Vasodilators. Scientific Reports. 2018; 8: 14604.","DOI":"10.1038\/s41598-018-32449-4"},{"key":"ref32","unstructured":"Yoshimura Y. Responses to vasocontractile agents in aorta and portal vein from stroke-prone SHR, especially in relation to aging. Acta medica Kinki University. 1986; 11: 67\u201383."},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Cheng Y, Zhao J, Tse HF, Le XC, Rong J. Plant Natural Products Calycosin and Gallic Acid Synergistically Attenuate Neutrophil Infiltration and Subsequent Injury in Isoproterenol-Induced Myocardial Infarction: a Possible Role for Leukotriene B4 12-Hydroxydehydrogenase? Oxidative Medicine and Cellular Longevity. 2015; 2015: 434052.","DOI":"10.1155\/2015\/434052"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"Qian J, Tian W, Jiang X, Tamosiuniene R, Sung YK, Shuffle EM, et al. Leukotriene B4 activates pulmonary artery adventitial fibroblasts in pulmonary Hypertension. Hypertension. 2015; 66: 1227\u20131239.","DOI":"10.1161\/HYPERTENSIONAHA.115.06370"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Fard MK, van der Meer F, S\u00e1nchez P, Cantuti-Castelvetri L, Mandad S, J\u00e4kel S, et al. BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions. Science Translational Medicine. 2017; 9: eaam7816.","DOI":"10.1126\/scitranslmed.aam7816"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Barral A, Rollan I, Sanchez-Iranzo H, Jawaid W, Badia-Careaga C, Menchero S, et al Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation. Biology Open. 2019; 8: bio046367.","DOI":"10.1242\/bio.046367"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Perota A, Galli C. N-glycolylneuraminic acid (Neu5Gc) null large animals by targeting the CMP-Neu5Gc hydroxylase (Cmah). Frontiers in Immunology. 2019; 10: 2396","DOI":"10.3389\/fimmu.2019.02396"},{"key":"ref38","doi-asserted-by":"crossref","unstructured":"Place DE, Malireddi RKS, Kim J, Vogel P, Yamamoto M, Kanneganti T. Osteoclast fusion and bone loss are restricted by interferon inducible guanylate binding proteins. Nature Communications. 2021; 12: 496.","DOI":"10.1038\/s41467-020-20807-8"},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Landrock KK, Sullivan P, Martini-Stoica H, Goldstein DS, Graham BH, Yamamoto S, et al. Pleiotropic neuropathological and biochemical alterations associated with Myo5a mutation in a rat Model. Brain Research. 2018; 1679: 155\u2013170.","DOI":"10.1016\/j.brainres.2017.11.029"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Ahn N, Kim W, Kim N, Park HW, Lee S, Yoo J. The Interferon-Inducible Proteoglycan Testican-2\/SPOCK2 Functions as a Protective Barrier against Virus Infection of Lung Epithelial Cells. Journal of Virology. 2019; 93: e00662-19.","DOI":"10.1128\/JVI.00662-19"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"Lacolley P, Regnault V, Segers P, Laurent S. Vascular Smooth Muscle Cells and Arterial Stiffening: Relevance in Development, Aging, and Disease. Physiological Reviews. 2017; 97: 1555\u20131617.","DOI":"10.1152\/physrev.00003.2017"},{"key":"ref42","doi-asserted-by":"crossref","unstructured":"Kinguchi S, Wakui H, Azushima K, Haruhara K, Koguchi T, Ohki K, et al. Effects of ATRAP in Renal Proximal Tubules on Angiotensin\u2010Dependent Hypertension. Journal of the American Heart Association. 2019; 8: e012395.","DOI":"10.1161\/JAHA.119.012395"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Zhang F, Xu Y, Pan Y, Sun S, Chen A, Li P, et al. Effects of angiotensin-(1-7) and angiotensin II on acetylcholine induced vascular relaxation in spontaneously hypertensive rats. Oxidative Medicine and Cellular Longevity. 2019; 2019: 6512485.","DOI":"10.1155\/2019\/6512485"}],"container-title":["Frontiers in Bioscience-Landmark"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/27\/6\/10.31083\/j.fbl2706191","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T12:05:25Z","timestamp":1732709125000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/27\/6\/10.31083\/j.fbl2706191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,15]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022]]}},"alternative-id":["S2768-6701(22)00556-1"],"URL":"https:\/\/doi.org\/10.31083\/j.fbl2706191","relation":{},"ISSN":["2768-6701","2768-6698"],"issn-type":[{"value":"2768-6701","type":"print"},{"value":"2768-6698","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,15]]},"article-number":"191"}}