Alpha-Adducin Gly460Trp polymorphism, left ventricular mass and plasma renin activity

Winnicki, Mikołaj; Somers, Virend K.; Accurso, Valentina; Hoffmann, Michal; Pawłowski, Ryszard; Frigo, Gianfranco; Visentin, Pieralberto; Palatini, Paolo

doi:10.1097/00004872-200209000-00021

Cited by 30 publications

(25 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ␣-, ␤-, and ␥-subunits of adducin are encoded by genes (ADD1, ADD2, and ADD3 or Add1, Add2, and Add3 in humans and rats, respectively) that map to different chromosomes (29, 50). The polymorphism of ADD1 (G460W/S586C) alone (or in combination with those of ADD2) and angiotensin-converting enzyme is associated with either essential hypertension (18,45,78) or with the related cardiovascular and renal complications (51,54,60,70,75).The Milan hypertensive strain (MHS) of rats is a genetic model of hypertension in which cardiovascular phenotypes seem to be dependent, at least in part, on adducin gene polymorphisms (11,62). In the MNS ϫ MHS F2 hybrid population, the mutation of the Add1 gene accounts for the 50% of the blood pressure (BP) difference between MHS and its normotensive counterpart (MNS) (9, 11).…”

mentioning

confidence: 99%

Upregulation of Na⁺/Ca²⁺exchanger and TRPC6 contributes to abnormal Ca²⁺homeostasis in arterial smooth muscle cells from Milan hypertensive rats

Zulian

Baryshnikov

Linde

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Zulian A, Baryshnikov SG, Linde CI, Hamlyn JM, Ferrari P, Golovina VA. Upregulation of Na ϩ /Ca 2ϩ exchanger and TRPC6 contributes to abnormal Ca 2ϩ homeostasis in arterial smooth muscle cells from Milan hypertensive rats. Am J Physiol Heart Circ Physiol 299: H624 -H633, 2010. First published July 9, 2010; doi:10.1152/ajpheart.00356.2010.-The Milan hypertensive strain (MHS) of rats is a model for hypertension in humans. Inherited defects in renal function have been well studied in MHS rats, but the mechanisms that underlie the elevated vascular resistance are unclear. Altered Ca 2ϩ signaling plays a key role in the vascular dysfunction associated with arterial hypertension. Here we compared Ca 2ϩ signaling in mesenteric artery smooth muscle cells from MHS rats and its normotensive counterpart (MNS). Systolic blood pressure was higher in MHS than in MNS rats (144 Ϯ 2 vs. 113 Ϯ 1 mmHg, P Ͻ 0.05). Resting cytosolic free Ca 2ϩ concentration (measured with fura-2) and ATP-induced Ca 2ϩ transients were augmented in freshly dissociated arterial myocytes from MHS rats. Ba 2ϩ entry activated by the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol (a measure of receptor-operated channel activity) was much greater in MHS than MNS arterial myocytes. This correlated with a threefold upregulation of transient receptor potential canonical 6 (TRPC6) protein. TRPC3, the other component of receptor-operated channels, was marginally, but not significantly, upregulated. The expression of TRPC1/5, components of store-operated channels, was not altered in MHS mesenteric artery smooth muscle. Immunoblots also revealed that the Na ϩ /Ca 2ϩ exchanger-1 (NCX1) was greatly upregulated in MHS mesenteric artery (by ϳ13-fold), whereas the expression of plasma membrane Ca 2ϩ -ATPase was not altered. Ca 2ϩ entry via the reverse mode of NCX1 evoked by the removal of extracellular Na ϩ induced a rapid increase in cytosolic free Ca 2ϩ concentration that was significantly larger in MHS arterial myocytes. The expression of ␣ 1/␣2 Na ϩ pumps in MHS mesenteric arteries was not changed. Immunocytochemical observations showed that NCX1 and TRPC6 are clustered in plasma membrane microdomains adjacent to the underlying sarcoplasmic reticulum. In summary, MHS arteries exhibit upregulated TRPC6 and NCX1 and augmented Ca 2ϩ signaling. We suggest that the increased Ca 2ϩ signaling contributes to the enhanced vasoconstriction and elevated blood pressure in MHS rats.adducin; hypertension; Milan normotensive rats; C-type transient receptor potential channels; receptor-operated calcium entry PRIMARY OR ESSENTIAL HYPERTENSION is a multifactorial disorder resulting from the complex interplay between genetic predisposition (genetic heritability, ϳ30%) and multiple environmental factors (1,44,71,74). The major difficulty in identifying genes contributing to hypertension is the etiological heterogeneity of hypertension (1). Genetic, physiological, and biochemical studies reveal that an alteration in the genes encoding adducin, a ubiquitously expressed membrane-ske...

show abstract

mentioning

confidence: 99%

Upregulation of Na⁺/Ca²⁺exchanger and TRPC6 contributes to abnormal Ca²⁺homeostasis in arterial smooth muscle cells from Milan hypertensive rats

Zulian

Baryshnikov

Linde

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…However, a tendency towards a better antihypertensive response with achievement of target levels of SBP and DBP was revealed in patients with Trp-allele of the ADD1 Gly460Trp polymorphism, which is in agreement with other studies. In addition, many patients, carriers of the Trp/Trp-genotype, were classified as carriers of a "low-renin" form of HT (66.7 %) compared with other patients (23.8%) [29,30]. In contrast to the well-designed study on the ADD1 Gly460Trp polymorphism, some other studies in other populations have shown insufficient results to confirm the same correlation between ADD1 polymorphism and sodium sensitivity [29,31] or a response to diuretic therapy [32], which causes great interest in continuing the investigations.…”

Section: Discussionmentioning

confidence: 99%

Alpha-Adducin Gly460Trp Polymorphism and Clinical Efficacy of Indapamide in Uzbek Hypertensive Patients

Abdullaeva¹,

Khamidullaeva²

2015

Int J Biomed

View full text Add to dashboard Cite

The purpose of the present study was to evaluate pharmacogenetic aspects of the antihypertensive, cardioprotective and vasoprotective efficacy of Indapamide in association with the ADD1 Gly460Trp polymorphism in Uzbek hypertensive patients. Materials and Methods:The study included 37 ethnic Uzbek patients (mean age of 47.14±9.54 years) with untreated Hypertension (HT) of Grade 1 and 2 (ESH/ESC, 2013) and average HT duration of 5.7±4.33 years. All patients underwent clinical examination, echocardiography, Doppler sonography study, assessment of flow-mediated dilation (FMD) of the brachial artery and microalbuminuria (MAU) in daily urine. Genomic DNA was extracted from peripheral blood using the Diatom TM DNA Prep 200 Kit according to the manufacturer's protocol. The PCR-RFLP technique with visualization was performed to determine the ADD1 Gly460Trp polymorphism. Indapamide was prescribed as monotherapy for 12 weeks with an initial dose of 2.5 mg.Results: A 12-week monotherapy with Indapamide in a daily dose of 2.5 mg showed the high antihypertensive efficacy of this drug expressing a reliable decrease in absolute values of SBP and DBP independently as carrying of the ADD1 Gly460Trp polymorphism allele. Positive changes in LVM during therapy in patients of both allele groups were accompanied by an improvement in LV diastolic function with significant positive dynamics of IRP. The target normalization of FMD was achieved only in the presence of Gly-allele, as well as a significant decrease in IMT and MAU during treatment. Conclusion:The results of our study showed high antihypertensive and cardioprotective efficacy of Indapamide treatment independently on carrying of the ADD1 Gly460Trp polymorphism. At the same time, we revealed certain advantages in the vasoprotective efficacy of Indapamide treatment in Uzbek hypertensive patients who are carriers of Gly-allele of the ADD1 Gly460Trp polymorphism. (Int J Biomed. 2015;5(3):132-136.)

show abstract

“…52 Most studies on left ventricular hypertrophy have been performed in Caucasians. 48,49,[53][54][55][56][57][58] The majority did not find an association. 49,54 -58 In contrast, studies in Chinese dialysis patients, 59 South Korean patients with chest discomfort or hypertension 60 and Japanese outpatients of a cardiovascular clinic 61 found an association between TT genotype and cardiac hypertrophy.…”

Section: Angiotensinogen M235t Polymorphismmentioning

confidence: 99%

Genetic polymorphisms and heart failure

Bleumink

Schut

Sturkenboom

et al. 2004

Genetics in Medicine

View full text Add to dashboard Cite

Heart failure is a complex clinical syndrome. There is evidence for a genetic contribution to the pathophysiology of heart failure. Considering the fundamental role of neurohormonal factors in the pathophysiology and progression of cardiac dysfunction and hypertrophy, variants of genes involved in this system are logical candidate genes in heart failure. In this report, genetic polymorphisms of the major neurohormonal systems in heart failure will be discussed. Studies on polymorphisms of the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous polymorphisms that may be involved in the development or phenotypic expression of heart failure will be reviewed. Research on left ventricular hypertrophy is also included. The majority of genetic association studies focused on the ACE I/D polymorphism.Initial genetic associations have often been difficult to replicate, mainly due to problems in study design and lack of power. Promising results have been obtained with genetic polymorphisms of the RAAS and sympathetic system.Considering the evidence so far, a modifying role for these polymorphisms seems more likely than a role of these variants as susceptibility genes. Besides the need for larger studies to examine the effects of single nucleotide polymorphisms and haplotypes, future studies also need to focus on the complexity of these systems and study Heart failure is a complex clinical syndrome with high morbidity and mortality. 1,2 Impairment of cardiac function activates compensatory neurohormonal mechanisms, which at a later stage may accelerate progression of heart failure. 3 Coronary heart disease and hypertension are major underlying causes of heart failure. Other frequent underlying conditions include valvular heart disease and idiopathic dilated cardiomyopathy. It is difficult to predict who will develop heart failure in response to myocardial injury. Racial differences in occurrence and outcome of heart failure 4,5 and heritability estimates of variability in left ventricular mass of 28% to 65% 6,7 suggest a genetic contribution to the pathophysiology of left ventricular remodeling and heart failure.Many studies have been published on the role of single gene mutations in (familial) cardiomyopathies. 8,9 These Mendelian traits are by nature rare, and although important at an individual level and for the understanding of disease mechanisms, are of limited significance in terms of prediction of heart failure occurrence in the population. 10 Moreover, in patients with identical gene mutations clinical manifestations of cardiomyopathy may differ. This suggests that probably also environmental and/or other genetic factors play a role.In this report, genetic polymorphisms of major neurohormonal systems involved in the pathophysiology of heart failure will be discussed, including the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous...

show abstract

Alpha-Adducin Gly460Trp polymorphism, left ventricular mass and plasma renin activity

Cited by 30 publications

References 36 publications

Upregulation of Na⁺/Ca²⁺exchanger and TRPC6 contributes to abnormal Ca²⁺homeostasis in arterial smooth muscle cells from Milan hypertensive rats

Upregulation of Na⁺/Ca²⁺exchanger and TRPC6 contributes to abnormal Ca²⁺homeostasis in arterial smooth muscle cells from Milan hypertensive rats

Alpha-Adducin Gly460Trp Polymorphism and Clinical Efficacy of Indapamide in Uzbek Hypertensive Patients

Genetic polymorphisms and heart failure

Contact Info

Product

Resources

About

Alpha-Adducin Gly460Trp polymorphism, left ventricular mass and plasma renin activity

Cited by 30 publications

References 36 publications

Upregulation of Na+/Ca2+exchanger and TRPC6 contributes to abnormal Ca2+homeostasis in arterial smooth muscle cells from Milan hypertensive rats

Upregulation of Na+/Ca2+exchanger and TRPC6 contributes to abnormal Ca2+homeostasis in arterial smooth muscle cells from Milan hypertensive rats

Alpha-Adducin Gly460Trp Polymorphism and Clinical Efficacy of Indapamide in Uzbek Hypertensive Patients

Genetic polymorphisms and heart failure

Contact Info

Product

Resources

About

Upregulation of Na⁺/Ca²⁺exchanger and TRPC6 contributes to abnormal Ca²⁺homeostasis in arterial smooth muscle cells from Milan hypertensive rats

Upregulation of Na⁺/Ca²⁺exchanger and TRPC6 contributes to abnormal Ca²⁺homeostasis in arterial smooth muscle cells from Milan hypertensive rats