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Volumn 13, Issue 1, 2011, Pages 36-45

Catecholamine storage vesicles: Role of core protein genetic polymorphisms in hypertension

Author keywords

Blood pressure; Catecholamine; CHGA; CHGB; Genetics; Granins; Heritability; Hypertension; SCG2

Indexed keywords

ADENINE; ALBUMIN; CATECHOLAMINE; CHROMOGRANIN A; CHROMOGRANIN B; CORE PROTEIN; CYTOSINE; ISOPROSTANE; SECRETOGRANIN II; THYMINE;

EID: 79551512487     PISSN: 15226417     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11906-010-0170-y     Document Type: Article
Times cited : (18)

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    • Naturally occurring human genetic variation in the 3′-untranslated region of the secretory protein chromogranin A is associated with autonomic blood pressure regulation and hypertension in a sex-dependent fashion
    • Here the authors defined the functional activity of common variant C+87T in the 3′-UTR of the CHGA mRNA, which has been associated with both BP elevation in the population and risk for hypertensive (nondiabetic) renal disease
    • • Chen Y, Rao F, Rodriguez-Flores JL, et al.: Naturally occurring human genetic variation in the 3′-untranslated region of the secretory protein chromogranin A is associated with autonomic blood pressure regulation and hypertension in a sex-dependent fashion. J Am Coll Cardiol 2008, 52:1468-1481. Here the authors defined the functional activity of common variant C+87T in the 3′-UTR of the CHGA mRNA, which has been associated with both BP elevation in the population and risk for hypertensive (nondiabetic) renal disease.
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    • Common functional genetic variants in catecholamine storage vesicle protein promoter motifs interact to trigger systemic hypertension
    • In this report, common variants and haplotypes of the CHGB promoter were functionally defined in transcriptional assays; such variants were strongly predictive of autonomic activity and BP in vivo
    • • Zhang K, Rao F, Wang L, et al.: Common functional genetic variants in catecholamine storage vesicle protein promoter motifs interact to trigger systemic hypertension. J Am Coll Cardiol 2010, 55:1463-1475. In this report, common variants and haplotypes of the CHGB promoter were functionally defined in transcriptional assays; such variants were strongly predictive of autonomic activity and BP in vivo.
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    • Zhang, K.1    Rao, F.2    Wang, L.3
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    • Antihypertensive treatments obscure familial contributions to blood pressure variation
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    • Isoprostane, an "intermediate phenotype" for oxidative stress heritability, risk trait associations, and the influence of chromogranin B polymorphism
    • A common variant (C+84A) in the 3′-UTR of the CHGB mRNA was associated with an "oxidative stress" phenotype: isoprostane excretion. The variant acted by disrupting an A/U-rich mRNA stability element
    • • Rao F, Zhang K, Khandrika S, et al.: Isoprostane, an "intermediate phenotype" for oxidative stress heritability, risk trait associations, and the influence of chromogranin B polymorphism. J Am Coll Cardiol 2010, 56:1338-1350. A common variant (C+84A) in the 3′-UTR of the CHGB mRNA was associated with an "oxidative stress" phenotype: isoprostane excretion. The variant acted by disrupting an A/U-rich mRNA stability element.
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    • Chromogranin A polymorphisms are associated with hypertensive renal disease
    • This was the initial report on the effect of CHGA polymorphisms on susceptibility to hypertensive renal disease in African Americans. The functional variant was at position C+87T in the CHGA mRNA
    • • Salem RM, Cadman PE, Chen Y, et al.: Chromogranin A polymorphisms are associated with hypertensive renal disease. J Am Soc Nephrol 2008, 19:600-614. This was the initial report on the effect of CHGA polymorphisms on susceptibility to hypertensive renal disease in African Americans. The functional variant was at position C+87T in the CHGA mRNA.
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    • Salem, R.M.1    Cadman, P.E.2    Chen, Y.3
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    • Chromogranin A regulates renal function by triggering Weibel-Palade body exocytosis
    • The authors found that CHGA influenced renal function by triggering generalized exocytosis from Weibel-Palade bodies, the hormone storage granules in endothelial cells
    • • Chen Y, Mahata M, Rao F, et al.: Chromogranin A regulates renal function by triggering Weibel-Palade body exocytosis. J Am Soc Nephrol 2009, 20:1623-1632. The authors found that CHGA influenced renal function by triggering generalized exocytosis from Weibel-Palade bodies, the hormone storage granules in endothelial cells.
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    • Chen, Y.1    Mahata, M.2    Rao, F.3
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    • Effects of chromogranin A deficiency and excess in vivo: Biphasic blood pressure and catecholamine responses
    • CHGA expression displays paradoxic relationships with BP: though human essential hypertension is associated with elevated plasma CHGA, targeted ablation of the Chga locus in the mouse also results in hypertension. In this study, the authors used gene targeting and replacement to systematically vary the copy number of CHGA from 0 to 4 copies per diploid genome, and the results established biphasic effects of CHGA copy number on catecholamine storage and release as well as on BP
    • • Vaingankar SM, Li Y, Biswas N, et al.: Effects of chromogranin A deficiency and excess in vivo: biphasic blood pressure and catecholamine responses. J Hypertens 2010, 28:817-825. CHGA expression displays paradoxic relationships with BP: though human essential hypertension is associated with elevated plasma CHGA, targeted ablation of the Chga locus in the mouse also results in hypertension. In this study, the authors used gene targeting and replacement to systematically vary the copy number of CHGA from 0 to 4 copies per diploid genome, and the results established biphasic effects of CHGA copy number on catecholamine storage and release as well as on BP.
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    • Global disturbances in autonomic function yield cardiovascular instability and hypertension in the chromogranin a null mouse
    • Targeted ablation of the Chga locus results in systemic hypertension in the mouse; this study defined widespread effects of such genetic deletion upon both the sympathetic and parasympathetic branches of the autonomic nervous system
    • • Gayen JR, Gu Y, O'Connor DT, Mahata SK: Global disturbances in autonomic function yield cardiovascular instability and hypertension in the chromogranin a null mouse. Endocrinology 2009, 150:5027-5035. Targeted ablation of the Chga locus results in systemic hypertension in the mouse; this study defined widespread effects of such genetic deletion upon both the sympathetic and parasympathetic branches of the autonomic nervous system.
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    • Chromogranin a and the autonomic system: Decomposition of heart rate variability and rescue by its catestatin fragment
    • Adjustment of heart rate upwards or downwards in response to endogenous and exogenous cues (heart rate variability, HRV) reflects a healthy autonomic system. After targeted ablation of the Chga gene in the mouse, HRV declines; the trait can be "rescued" by replacement of the catestatin fragment of CHGA
    • • Dev NB, Gayen JR, O'Connor DT, Mahata SK: Chromogranin a and the autonomic system: decomposition of heart rate variability and rescue by its catestatin fragment. Endocrinology 2010, 151:2760-2768. Adjustment of heart rate upwards or downwards in response to endogenous and exogenous cues (heart rate variability, HRV) reflects a healthy autonomic system. After targeted ablation of the Chga gene in the mouse, HRV declines; the trait can be "rescued" by replacement of the catestatin fragment of CHGA.
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    • A novel pathway of insulin sensitivity in chromogranin A null mice: A crucial role for pancreastatin in glucose homeostasis
    • In the mouse, knockout of the Chga gene (Chga-/- genotype) results in a peculiar combination of elevated blood pressure coupled with enhanced insulin sensitivity, especially in the liver. Chga encodes a dysglycemic fragment, named "pancreastatin"; administration of this peptide to Chga-/- mice reversed the insulin sensitivity of the knockout state
    • • Gayen JR, Saberi M, Schenk S, et al.: A novel pathway of insulin sensitivity in chromogranin A null mice: a crucial role for pancreastatin in glucose homeostasis. J Biol Chem 2009, 284:28498-28509. In the mouse, knockout of the Chga gene (Chga-/- genotype) results in a peculiar combination of elevated blood pressure coupled with enhanced insulin sensitivity, especially in the liver. Chga encodes a dysglycemic fragment, named "pancreastatin" ; administration of this peptide to Chga-/- mice reversed the insulin sensitivity of the knockout state.
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    • Here the authors profiled the transcriptome in mice after targeted ablation of the Chga locus, and thereby identified global patterns of mRNA expression subserving enhanced insulin sensitivity in this animal model
    • • Friese RS, Gayen JR, Mahapatra NR, et al.: Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification. Physiol Genomics 2010, 40:195-207. Here the authors profiled the transcriptome in mice after targeted ablation of the Chga locus, and thereby identified global patterns of mRNA expression subserving enhanced insulin sensitivity in this animal model.
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    • Here the authors defined commonly occurring, natural genetic variation across the human CHGB locus, including promoter variants predicting elevated BP. In a complementary study, targeted ablation of the mouse Chgb locus resulted in systemic hypertension
    • • Zhang K, Rao F, Rana BK, et al.: Autonomic function in hypertension: Role of genetic variation at the catecholamine storage vesicle protein chromogranin B (CHGB). Circ Cardiovasc Genet 2009, 2:46-56. Here the authors defined commonly occurring, natural genetic variation across the human CHGB locus, including promoter variants predicting elevated BP. In a complementary study, targeted ablation of the mouse Chgb locus resulted in systemic hypertension.
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* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.