Gly460Trp α-adducin gene polymorphism and endothelial function in untreated hypertensive patients

Perticone, Francesco; Sciacqua, Angela; Barlassina, Cristina; Vecchio, Lucia Del; Signorello, Maria Chiara; Fiume, Chiara Dal; Andreozzi, Francesco; Sesti, Giorgio; Cusi, Daniele

doi:10.1097/hjh.0b013e3282ef3a50

Cited by 11 publications

(11 citation statements)

References 18 publications

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“…30 Adducin may then exert a pleiotropic effect, both on the development of hypertension and on organ damage, as an endothelial dysfunction, through its effect on adhesion molecules, caused by a constitutive change in their cell-surface expression and by altering intracellular signals. 8 A second interesting finding of this study is the observation of quantitative and qualitative changes in the pattern of contractile response to NE in mesenteric small arteries of the MHS. It was shown earlier that, in adducin-dependent hypertension, alterations in the vascular Na+-K+-ATPase are present and may be responsible for an increased vascular contractility.…”

Section: Adducin and Small Artery Remodeling D Rizzoni Et Almentioning

confidence: 65%

“…As mentioned earlier, a possible role of a-adducin polymorphisms in the development of endothelial dysfunction was postulated in a population of essential hypertensives. 8 The mechanisms involved are still unclear, although it was hypothesized earlier that oxidative stress may be increased in the essential hypertensives carrying the 460Trp allele of Add1. 29 Other mechanisms possibly involved are related to effects of the mutated adducin on the density of integrins and adhesion molecules on the cell surface.…”

Section: Adducin and Small Artery Remodeling D Rizzoni Et Almentioning

confidence: 99%

“…Recently, an association between endothelium-dependent dilatation in the forearm and the 460Trp allele was observed in a population of essential hypertensives. 8 The Milan hypertensive rat strain (MHS), and its normotensive counterpart (MNS) are a good animal model for studying the role of adducin in the development of hypertension. 1,2 In an analogy with the human situation, transplantation of a kidney from an MNS donor to an MHS recipient, reduced blood pressure (and increased sodium excretion) and vice versa.…”

Section: Introductionmentioning

confidence: 99%

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Functional alterations of mesenteric small resistance arteries in Milan hypertensive and normotensive rats

et al. 2009

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The Milan hypertensive rat strain (MHS) is a genetic strain in which cardiovascular phenotypes seem to be dependent, at least in part, on adducin gene polymorphisms. The aim of our study was to evaluate the structure, contractile responses and endothelium-dependent vasodilation in mesenteric small resistance arteries in 12-week-old MHS, (n¼7), age-matched Milan normotensive rats (MNS, n¼7) and congenic strains in which the DNA segments carrying the a-adducin locus from the MHS have been introgressed into the MNS (MNA, n¼7). Systolic blood pressure (tail cuff) and left ventricular weight to body weight were measured. Mesenteric small arteries were dissected and mounted on a micromyograph; the media:lumen ratio was then calculated. Concentration-response curves to acetylcholine and to norepinephrine (NE) were created. Systolic blood pressure was significantly increased in the MHS and MNA strains compared with the MNS. No significant difference in mesenteric small resistance artery structure was observed among the groups; however, a slightly more elevated media:lumen ratio was observed in MNA compared with the MNS. In contrast, left ventricular weight to body weight was significantly increased and ACH-induced dilatation was significantly impaired in the MHS and in MNA compared with MNS. The concentration-response curve to NE in the MHS showed significantly reduced sensitivity to NE; however, maximum contraction was increased in the MHS vs. the other groups. The MHS presents cardiac (but not vascular) remodeling, endothelial dysfunction and a peculiar contractile response to NE, compared with the other groups. The systolic blood pressure increase and trend to vascular remodeling in MNA support the pathogenic role of a-adducin.

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Section: Adducin and Small Artery Remodeling D Rizzoni Et Almentioning

confidence: 65%

Section: Adducin and Small Artery Remodeling D Rizzoni Et Almentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Functional alterations of mesenteric small resistance arteries in Milan hypertensive and normotensive rats

et al. 2009

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“…Investigations of the EPOGH project provided evidence that peripheral and central pulse pressures were elevated in carriers of the ADD1Trp amino acid [24] while the association of brachial diameter was detected in a multiple-gene analyses of ADD1 wt homozygotes and the ADD3 G allele (rs3731566) [116]. The group of Cusi [95] reported for the first time that 460Trp was associated with blunted endothelium-dependent vasodilation in a group of untreated patients with essential hypertension.…”

Section: Alpha-adducin and Actin-based Cytoskeleton Dynamicsmentioning

confidence: 96%

Salt controls endothelial and vascular phenotype

Kusche-Vihrog

Schmitz

Brand

2014

Pflugers Arch - Eur J Physiol

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High salt (NaCl) intake promotes the development of vascular diseases independent of a rise in blood pressure, whereas reduction of salt consumption has beneficial effects for the arterial system. This article summarizes our current understanding of the molecular mechanisms of high salt-induced alterations of the endothelial phenotype, the impact of the individual endothelial genotype, and the overall vascular phenotype. We focus on the endothelial Na(+) channel (EnNaC)-controlled nanomechanical properties of the endothelium, since high Na(+) leads to an EnNaC-induced Na(+)-influx and subsequent stiffening of endothelial cells. The mechanical stiffness of the endothelial cell (i.e., the endothelial phenotype) plays a crucial role as it controls the production of the endothelium-derived vasodilator nitric oxide (NO) which directly affects the tone of the vascular smooth muscle cells. In contrast to soft endothelial cells, stiff endothelial cells release reduced amounts of NO, the hallmark of endothelial dysfunction. This endothelium-born process is followed by the development of arterial stiffness (i.e., the vascular phenotype), predicting the development of vascular end-organ damage such as myocardial infarction, stroke, and renal impairment. In this context, we outline the potential clinical implication of direct (amiloride) and indirect (spironolactone) EnNaC inhibition on vascular function. However, interindividual differences exist in the response to high salt intake which involves different endothelial genotypes. Thus, selected genes and genetic variants contributing to the development of salt-induced endothelial dysfunction and hypertension are discussed. In this review, we focus on the role of salt in endothelial and vascular (dys)function and the link between salt-induced changes of the endothelial and vascular phenotype and its clinical implications.

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“…The protocol previously described by Panza et al (2) and subsequently used by our group (3,5,6,9) was used for the study presented here. All patients underwent measurement of FBF and BP during intra-arterial infusion of saline, acetylcholine (ACh), and sodium nitroprusside (SNP) at increasing doses.…”

Section: Vascular Functionmentioning

confidence: 99%

Association between Hemoglobin Level and Endothelial Function in Uncomplicated, Untreated Hypertensive Patients

Maio¹,

Sciacqua²,

Bruni³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Hemoglobin (Hb) is an important nitric oxide (NO) buffer and a modulator of NO bioavailability. In addition, endothelial dysfunction is common in hypertensive patients, suggesting a pivotal role of hemoglobin concentration ([Hb]) in vascular function. To investigate the potential role of [Hb] in endothelium-dependent vasodilation, the relationship between Hb and endothelial function was tested in a group of patients with essential hypertension. Design, setting, participants, & measurementsIn this retrospective study, 174 nonsmoking, uncomplicated, never-treated hypertensives were enrolled. Endothelium-dependent and -independent vasodilation was assessed by measurement of forearm blood flow response during intra-arterial infusion of increasing doses of acetylcholine (ACh) and sodium nitroprusside (SNP) using strain-gauge plethysmography. Correlation with established risk factors of endothelial dysfunction was performed. ResultsThe vasodilatory response to ACh was inversely (P Ͻ 0.001) related to [Hb], and this relationship was dose dependent (P Ͻ 0.001), being minimal at the lowest dose and maximal at the highest dose. No association was found between Hb and the vasodilatory response to SNP. In a multiple linear regression model adjusted for Framingham risk factors (age, sex, BP, cholesterol, body mass index, glucose) and emerging risk factors (homeostasis model assessment index, C-reactive protein, estimated GFR), [Hb] maintained a strong and independent link with the vasodilatory response to ACh (P Ͻ 0.001). ConclusionsIn a large group of nonsmoking untreated hypertensives, [Hb] is inversely related to forearm endothelium-dependent vasodilation. [Hb] should be taken into account, especially in conditions associated with low [Hb], when performing vascular function studies.

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Gly460Trp α-adducin gene polymorphism and endothelial function in untreated hypertensive patients

Abstract: The main finding in this study was that in essential hypertensives the 460Trp allele of ADD1 is strongly associated with an impaired endothelium-dependent vasodilation, a powerful predictor of cardiovascular risk.

Cited by 11 publications

References 18 publications

Functional alterations of mesenteric small resistance arteries in Milan hypertensive and normotensive rats

Functional alterations of mesenteric small resistance arteries in Milan hypertensive and normotensive rats

Salt controls endothelial and vascular phenotype

Association between Hemoglobin Level and Endothelial Function in Uncomplicated, Untreated Hypertensive Patients

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