The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Hypertension from targeted ablation of chromogranin A can be rescued by the human ortholog
Open accessAbstract
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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Cites
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Continuous Relation Between Left Ventricular Mass and Cardiovascular Risk in Essential Hypertension
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Dense-core secretory granule biogenesis
Kim, T., Gondré-Lewis, M. C., Arnaoutova, I., & Loh, Y. P. (2006) · Physiology · doi:10.1152/physiol.00043.2005 · Cited by 203
Sending proteins to dense core secretory granules: still a lot to sort out
Dikeakos, J. D., & Reudelhuber, T. L. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200701024 · Cited by 131
Biogenesis of secretory granules
Borgonovo, B., Ouwendijk, J., & Solimena, M. (2006) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2006.06.010 · Cited by 100
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Metadata
- Authors
- Mahapatra, N. R., O’Connor, D. T., Vaingankar, S. M., Hikim, A. P. S., Mahata, M., Ray, S., Staite, E., Wu, H., Gu, Y., Dalton, N., Kennedy, B. P., Ziegler, M. G., Ross, J., & Mahata, S. K.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-07-01
- Volume
- 115
- Issue
- 7
- Pages
- 1942-1952
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2157377175
- Cited by
- 309
- References
- 55
- FWCI
- 12.94
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Mahapatra, N. R., O’Connor, D. T., Vaingankar, S. M., Hikim, A. P. S., Mahata, M., Ray, S., Staite, E., Wu, H., Gu, Y., Dalton, N., Kennedy, B. P., Ziegler, M. G., Ross, J., & Mahata, S. K. (2005). Hypertension from targeted ablation of chromogranin A can be rescued by the human ortholog. Journal of Clinical Investigation. https://doi.org/10.1172/jci24354
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