Alpha‐adrenergic receptor gene polymorphisms and cardiovascular reactivity to stress in <scp>B</scp>lack adolescents and young adults

Kelsey, Robert M.; Alpert, Bruce S.; Dahmer, Mary K.; Krushkal, Julia; Quasney, Michael W.

doi:10.1111/j.1469-8986.2011.01319.x

Cited by 25 publications

(16 citation statements)

References 109 publications

(212 reference statements)

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“…Polymorphisms in genes involved in regulation of the adrenergic system, including α 1a AR gene, have been linked to hypertensive disorders [12,24,25]. Functional effects of α 1a AR SNPs might therefore represent a novel mechanism underlying hypertension and heart disease.…”

Section: Introductionmentioning

confidence: 99%

Alpha1a-adrenoceptor genetic variant induces cardiomyoblast-to-fibroblast-like cell transition via distinct signaling pathways

Kleine‐Brueggeney

Grădinaru

Babaeva

et al. 2014

Cellular Signalling

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The role of naturally occurring human α1a-Adrenergic Receptor (α1aAR) genetic variants associated with cardiovascular disorders is poorly understood. Here, we present the novel findings that expression of human α1aAR-247R (247R) genetic variant in cardiomyoblasts leads to transition of cardiomyoblasts into a fibroblast-like phenotype, evidenced by morphology and distinct de novo expression of characteristic genes. These fibroblast-like cells exhibit constitutive, high proliferative capacity and agonist-induced hypertrophy compared with cells prior to transition. We demonstrate that constitutive, synergistic activation of EGFR, Src and ERK kinases is the potential molecular mechanism of this transition. We also demonstrate that 247R triggers two distinct EGFR transactivation-dependent signaling pathways: 1) constitutive Gq-independent βarrestin1/Src/MMP/EGFR/ERK-dependent hyperproliferation and 2) agonist-induced Gq- and EGFR/STAT-dependent hypertrophy. Interestingly, in cardiomyoblasts agonist-independent hyperproliferation is MMP-dependent, but in fibroblast-like cells it is MMP-independent, suggesting that expression of α1aAR genetic variant in cardiomyocytes may trigger extracellular matrix remodeling. Thus, these novel findings demonstrate that EGFR transactivation by α1aAR-247R leads to hyperproliferation, hypertrophy and alterations in cardiomyoblasts, suggesting that these unique genetically-mediated alterations in signaling pathways and cellular function may lead to myocardial fibrosis. Such extracellular matrix remodeling may contribute to the genesis of arrhythmias in certain types of heart failure.

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Section: Introductionmentioning

confidence: 99%

Alpha1a-adrenoceptor genetic variant induces cardiomyoblast-to-fibroblast-like cell transition via distinct signaling pathways

Kleine‐Brueggeney

Grădinaru

Babaeva

et al. 2014

Cellular Signalling

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“…(30) Moreover, it has been associated with other α 2A -AR-related phenotypes suggesting a gain-of-function action such as schizophrenia, weight gain during antipsychotic medication use, body fat accumulation, and vascular reactivity to stress. (31–34) The variant is in the promoter region of the gene, and it may exert its effects by influencing gene expression. (35) In keeping with previous findings related to glucose regulation phenotypes,(31–34) we found that the G allele was associated with higher admission glucose in Caucasians (P = 0.046) with a similar trend among African-American subjects.…”

Section: Discussionmentioning

confidence: 99%

“…(31–34) The variant is in the promoter region of the gene, and it may exert its effects by influencing gene expression. (35) In keeping with previous findings related to glucose regulation phenotypes,(31–34) we found that the G allele was associated with higher admission glucose in Caucasians (P = 0.046) with a similar trend among African-American subjects.…”

Section: Discussionmentioning

confidence: 99%

Alpha2A adrenergic receptor genetic variation contributes to hyperglycemia after myocardial infarction

Adefurin

Darghosian

Okafor

et al. 2016

International Journal of Cardiology

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Background Acute myocardial infarction (AMI) is frequently associated with transient hyperglycemia even in patients without pre-existing diabetes. Acute stress can lead to increased blood glucose through the effect of catecholamines on alpha2A-adrenergic receptors (α2A-ARs) present in pancreatic islet β-cells. Variation in the gene (ADRA2A) that encodes the α2A-AR affects insulin release and glucose control and may play a particularly important role during times of stress. Methods We performed a retrospective cohort study using de-identified electronic medical records linked to a DNA repository in 521 Caucasians and 55 African-American non-diabetic patients with AMI. We examined the association between admission blood glucose concentrations and ten selected ADRA2A SNPs in Caucasians. Results Three ADRA2A SNPS were associated with stress-induced hyperglycemia in Caucasians. Individuals homozygous for the rs10885122 variant (n=9) had a 23% lower admission glucose (geometric mean [95% CI], 99 [83 – 118] mg/dl) compared with non-carriers (121 [118–125] mg/dl; n=401; P = 0.001). Admission glucose was 14% higher in rs1800544 variant homozygotes (134 [119–150] mg/dl; n=36) compared to non-carriers (118 [115–121] mg/dl; n=290, P=0.046). Furthermore, homozygotes of the rs553668 variant (n = 13) had a 13% higher glucose (133 [110–160] mg/dl) compared to non-carriers (118 [115–122] mg/dl; n=366; P = 0.056). Haplotypes including these ADRA2A SNPs were associated with higher admission glucose levels. Conclusions Three ADRA2A genetic variants are associated with blood glucose and stress-induced hyperglycemia after AMI in Caucasians.

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“…To address this point, Kelsey et al evaluated associations between three genetic polymorphisms within the α1-, α2A and α2B-ARs genes (Arg492Cys, C-1291G, and Ins/Del301-303, respectively) and cardiovascular reactivity to stress in healthy, normotensive black adolescents as well as in young adults [62]. The psychological stressors used in this study consisted of mental arithmetic tasks and a video game task.…”

Section: α-And β-Adrenergic Receptors (Adra and Adrb) Genesmentioning

confidence: 99%

Searching for genes involved in hypertension development in special populations: children and pre-eclamptic women. Where are we standing now?

Danese¹,

Montagnana²,

Fava³

2013

Clinical Chemistry and Laboratory Medicine (CCLM)

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Primary hypertension is a very common disorder particularly in the aging population but hypertensive disorders can appear earlier in life, especially when obesity and unhealthy lifestyle are present. Also pregnant women can be at risk of developing gestational hypertension and/or pre-eclampsia, which causes complications in nearly 7% of pregnancies. These "special" populations could be regarded as natural models suited to reveal mechanisms of hypertension development which are either common to other forms of hypertension, including primary hypertension or specific to these populations. Recent studies in the field of genetics of primary hypertension have used new powerful tools, such as genome-wide association studies (GWAS) and sequencing, but studies about hypertension during childhood and in pregnancy have seldom used high-throughput technologies and the knowledge in this field comes mostly from the candidate gene approach. In this review we summarize some interesting results from genetic studies conducted in childhood and adolescence and during pregnancy and underline the need to apply modern technologies in these potentially very fruitful populations.

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Alpha‐adrenergic receptor gene polymorphisms and cardiovascular reactivity to stress in Black adolescents and young adults

Cited by 25 publications

References 109 publications

Alpha1a-adrenoceptor genetic variant induces cardiomyoblast-to-fibroblast-like cell transition via distinct signaling pathways

Alpha1a-adrenoceptor genetic variant induces cardiomyoblast-to-fibroblast-like cell transition via distinct signaling pathways

Alpha2A adrenergic receptor genetic variation contributes to hyperglycemia after myocardial infarction

Searching for genes involved in hypertension development in special populations: children and pre-eclamptic women. Where are we standing now?

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