| Hypertension from targeted ablation of chromogranin A can be rescued by the human ortholog. | |
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MedLine Citation:
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PMID: 16007257 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The secretory prohormone chromogranin A (CHGA) is overexpressed in essential hypertension, a complex trait with genetic predisposition, while its catecholamine release-inhibitory fragment catestatin is diminished, and low catestatin predicts augmented adrenergic pressor responses. These findings from studies on humans suggest a mechanism whereby diminished catestatin might increase the risk for hypertension. We generated Chga and humanized mice through transgenic insertion of a human CHGA haplotype in order to probe CHGA and catestatin in vivo. Chga mice displayed extreme phenotypic changes, including: (a) decreased chromaffin granule size and number; (b) elevated BP; (c) loss of diurnal BP variation; (d) increased left ventricular mass and cavity dimensions; (e) decreased adrenal catecholamine, neuropeptide Y (Npy), and ATP contents; (f) increased catecholamine/ATP ratio in the chromaffin granule; and (g) increased plasma catecholamine and Npy levels. Rescue of elevated BP to normalcy was achieved by either exogenous catestatin replacement or humanization of Chga mice. Loss of the physiological "brake" catestatin in Chga mice coupled with dysregulation of transmitter storage and release may act in concert to alter autonomic control of the circulation in vivo, eventuating in hypertension. |
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Authors:
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Nitish R Mahapatra; Daniel T O'Connor; Sucheta M Vaingankar; Amiya P Sinha Hikim; Manjula Mahata; Saugata Ray; Eugenie Staite; Hongjiang Wu; Yusu Gu; Nancy Dalton; Brian P Kennedy; Michael G Ziegler; John Ross; Sushil K Mahata |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 115 ISSN: 0021-9738 ISO Abbreviation: J. Clin. Invest. Publication Date: 2005 Jul |
Date Detail:
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Created Date: 2005-07-11 Completed Date: 2005-08-31 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 1942-52 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine, UCSD, San Diego, CA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / physiology Chromaffin Granules / pathology, physiology Chromogranin A Chromogranins / genetics*, physiology* Circadian Rhythm Corticosterone / blood Epinephrine / blood Gene Targeting Humans Hypertension / etiology*, genetics*, pathology, physiopathology Hypertrophy, Left Ventricular / pathology Mice Mice, Knockout Mice, Transgenic Microscopy, Electron Neuropeptide Y / blood Norepinephrine / blood Renin / blood |
| Grant Support | |
ID/Acronym/Agency:
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DK 60702/DK/NIDDK NIH HHS; HD 39293/HD/NICHD NIH HHS; P01 HL58120/HL/NHLBI NIH HHS; R29 DA11311/DA/NIDA NIH HHS; U01 HL69758/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CHGA protein, human; 0/Chromogranin A; 0/Chromogranins; 0/Neuropeptide Y; 0/chromogranin A, mouse; 50-22-6/Corticosterone; 51-41-2/Norepinephrine; 51-43-4/Epinephrine; EC 3.4.23.15/Renin |
| Comments/Corrections | |
Comment In:
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J Clin Invest. 2005 Jul;115(7):1711-3
[PMID:
16007250
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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