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            Allele of the Angiotensin I–Converting Enzyme Is a Major Risk Factor for Restenosis After Coronary Stenting

Amant, Carole; Bauters, Christophe; Bodart, Jean-Christophe; Lablanche, Jean‐Marc; Grollier, Gilles; Danchin, Nicolás; Hamon, Martial; Richard, Florence; Helbecque, Nicole; McFadden, Eugène; Amouyel, Philippe; Bertrand, Michel E.

doi:10.1161/01.cir.96.1.56

Cited by 142 publications

(91 citation statements)

References 27 publications

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“…Nevertheless, experimental 64,65 and clinical 66 studies have suggested that the contribution of neointimal hyperplasia to restenosis after balloon angioplasty is relatively limited and that lumen renarrowing is in fact related primarily to vessel remodeling. Amant and coworkers 67 recently demonstrated that the D allele of the ACE gene is associated with a greater late luminal loss after intracoronary stent implantation. In this case the stent prevents the remodeling process, and restenosis is primarily a consequence of neointimal hyperplasia within the stent.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin I-Converting Enzyme Genotype Influences Arterial Response to Injury in Normotensive Rats

Challah

Villard

Philippe

et al. 1998

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Abstract-Two normotensive strains of rat, the Lou and Brown Norway (BN) strains, have contrasting levels of plasma angiotensin-converting enzyme (ACE). To investigate the degree of genetic determination of ACE expression, a polymorphic marker of the ACE gene was analyzed in inbred rats of the two strains. The two inbred strains were shown to bear different alleles for a polymorphic marker at the ACE gene. The segregation of the alleles of this marker and the plasma ACE levels were studied in a group of F2 rats issued from a cross between Lou and BN rats. The degree of genetic determination of plasma ACE activity was estimated to be 94% in the F2 cohort. The ACE locus accounts for 74% of total plasma ACE variance. ACE activity and mRNA expression in lungs were also genetically determined. The difference observed in ACE mRNA accumulation in the lungs between the two strains was due to a difference in the transcriptional rate of the ACE gene, as shown in nuclear run-on experiments. No differences were observed in arterial blood pressure of homozygous F2 progeny. In these animals, ACE genotype did not interfere with the pressor or the depressor responses to ACE-dependent vasoactive peptides. There was a significant effect of strain on constitutive or inducible membrane or soluble ACE activity in primary cultures of vascular cells. Neointima formation in the carotid artery 14 days after balloon injury was also influenced by the genotype in F2 homozygous progeny, whereas the medial area was not. These results demonstrate that there is a close relationship between the genetically determined ACE expression and the inducibility of the ACE gene. The degree of genetic determination of ACE expression in inbred rat strains offers a unique opportunity to study the interaction between genetic and environmental determinants of ACE expression and its involvement in response to experimental cardiovascular and renal injury. (Arterioscler Thromb Vasc Biol. 1998;18:235-243.)

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Section: Discussionmentioning

confidence: 99%

Angiotensin I-Converting Enzyme Genotype Influences Arterial Response to Injury in Normotensive Rats

Challah

Villard

Philippe

et al. 1998

ATVB

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“…The ACE I/D polymorphism has been linked to various functional effects, for example the DD genotype being associated with high plasma ACE levels in addition to numerous diseases. One of the most extensively studied associations is with cardiovascular diseases, including myocardial infarction (Cambien et al, 1992 ;Nakai et al, 1994), left ventricular hypertrophy and dysfunction (Schunkert et al, 1994), dilated cardiomyopathy (Raynolds et al, 1993;Harn et al, 1995) hypertrophic cardiomyopathy (Marian et al, 1993), carotid thickening (Castellano et al, 1995;Kauma et al, 1996), venous thrombosis (Philipp et al, 1998), nephropathy (Schmidt & Ritz, 1997) and coronary restenosis after stent implantation (Amant et al, 1997). Currently, the best evidence for an association with the ACE I/D polymorphism is with arterial hypertension in men (Fornage et al, 1988 ;Higaki et al, 2000) ; one study of male carriers of the DD genotype showed a 1 .…”

Section: Introductionmentioning

confidence: 99%

The geographic distribution of the ACE II genotype: a novel finding

2007

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SummaryAngiotensin converting enzyme (ACE) gene polymorphism insertion (I) or deletion (D) has been widely studied in different populations, and linked to various functional effects and associated with common diseases. The purpose of the present study was to investigate the relationship between the ACE I/D frequency in different populations and geographic location; ACE I/D allele frequency in the Lebanese population and ACE II genotype contribution to the geographic trend were also identified. Five hundred and seventy healthy volunteers were recruited from the Lebanese population. Genomic DNA was extracted from buccal cells, and amplified by polymerase chain reaction; products were then identified by gel electrophoresis. The frequencies of the different ACE I/D genotypes were determined and tested for Hardy-Weinberg equilibrium (HWE). To assess the relationship between ACE I/D frequency and geographic location, and to identify how the Lebanese population contributes to the geographic trend in ACE I/D frequencies, Eurasian population samples and Asians were incorporated in the analyses from the literature. The frequency of the I allele in the Lebanese population was 27% and the corresponding II genotype was at a frequency of 7 . 37% (in HWE ; P=0 . 979). The ACE I allele and genotype frequencies show an association with longitude, with frequencies increasing eastwards and westwards from the Middle East.

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“…This suggests the presence of a higher level of vascular oxidative stress in people with the D allele, which might explain why they develop a higher incidence of vascular diseases such as restenosis after coronary angioplasty 42,43 or the higher risk of hypertension that is observed in men. 44,45 In addition, this phenotype depends on the AT 1 receptor stimulation, which can be blocked.…”

Section: Perspectivesmentioning

confidence: 99%

Increased Aortic NADPH Oxidase Activity in Rats With Genetically High Angiotensin-Converting Enzyme Levels

et al. 2005

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Abstract-In humans and rats, angiotensin I-converting enzyme activity is significantly determined by a gene polymorphism. Homozygous Brown Norway rats have higher plasma angiotensin I-converting enzyme activity and circulating angiotensin II (Ang II) levels than Lewis rats. Because Ang II induces NAD(P)H oxidase activation, we hypothesized here that Brown Norway rats have higher vascular NAD(P)H oxidase activity and superoxide anion production than Lewis rats. Homozygous Brown Norway (nϭ15) and Lewis (nϭ13) male rats were used. Plasma angiotensin I-converting enzyme activity (by fluorimetry), Ang II levels (by high-performance liquid chromatography and radioimmunoassay), and aortic NAD(P)H oxidase activity, as well as superoxide anion production (by chemiluminescence with lucigenin) were measured. Plasma angiotensin I-converting enzyme activity and Ang II levels were 100% higher in Brown Norway rats than in Lewis rats (PϽ0.05). Aortic angiotensin I-converting enzyme, but not Ang II, was elevated (PϽ0.05). Aortic superoxide anion production and NAD(P)H oxidase activity were 300% and 260% higher in Brown Norway than in Lewis rats, respectively (PϽ0.05), which was not observed in Brown Norway rats treated with candesartan (10 mg/kg per day for 7 days). Endothelial NO synthase activity in the aorta from Brown Norway rats was significantly lower than in Lewis rats. However, inducible NO synthase activity and both endothelial NO synthase and inducible NO synthase mRNA and protein levels were similar in both genotypes. In summary, Brown Norway rats have higher vascular NAD(P)H oxidase activity and superoxide anion production than Lewis rats, suggesting the presence of a higher level of vascular oxidative stress in rats with genetically higher angiotensin I-converting enzyme levels. This effect is mediated through the angiotensin I receptor.

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D Allele of the Angiotensin I–Converting Enzyme Is a Major Risk Factor for Restenosis After Coronary Stenting

Abstract: The ACE I/D polymorphism influences the level of late luminal loss after coronary stent implantation. These results suggest that the renin-angiotensin system may be implicated in the pathogenesis of restenosis after coronary stenting.

Cited by 142 publications

References 27 publications

Angiotensin I-Converting Enzyme Genotype Influences Arterial Response to Injury in Normotensive Rats

Angiotensin I-Converting Enzyme Genotype Influences Arterial Response to Injury in Normotensive Rats

The geographic distribution of the ACE II genotype: a novel finding

Increased Aortic NADPH Oxidase Activity in Rats With Genetically High Angiotensin-Converting Enzyme Levels

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