ACE DD genotype and restenosis

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ACE DD genotype and restenosis

Postby Anonymoose » Tue Dec 25, 2012 8:07 pm

ACE DD genotype may increase MS risk in males (abstract in Aldo and MS thread). This article outlines connection between restenosis after stenting and ACE DD genotype.

ACE Polymorphism and Coronary Restenosis after Stent Implantation
Intracoronary stent implantation has been shown to reduce the rate of coronary restenosis, a major postinterventional complication after balloon angioplasty. 76, 77 However, a minority of patients still develop coronary restenosis poststenting. Baseline preintervention patient parameters, however, are not good predictors of restenosis. The role of diabetes and unstable angina, which are demonstrated to increase the risk of restenosis after balloon angioplasty, is controversial in poststent restenosis. Unlike restenosis postangioplasty, which is primarily due to vessel constriction and remodeling, restenosis after stenting is primarily due to neointimal hyperplasia. 26, 78, 79, 80 This makes stent implantation a good model for the study of factors that may cause, promote, or block neointimal hyperplasia.

Because RAS has been implicated in the development of neointimal hyperplasia, 81 ACE activity is a crucial step for the RAS pathway, and the resulting increased generation of Ang II is a potent growth factor for smooth muscle cells, 82 the hypothesis has been advanced that genetic factors affecting RAS and particularly ACE gene expression may be important in pathogenesis of coronary restenosis after stenting. Indirect experimental evidence was obtained by demonstrating that ACE inhibitors block neointimal thickening after arterial balloon denudation in rats, guinea pigs, and rabbits. 83, 84 The clinical relation between restenosis after coronary stenting and ACE polymorphism was investigated by Amant et al 78 in 146 patients who underwent successful stent implantation and had 6 months’ follow-up angiography. The minimal lumen loss and late luminal loss had a significant inverse relationship to the D allele dose; the OR for restenosis was 2.0 per number of D alleles; the association of the number of D alleles and poststent restenosis was independent of other risk factors. 78 The increased ACE activity due to the presence of the D allele, mainly in the homozygous state, may account for the higher degree of coronary neointimal thickening found in these patients. 78 These results are in keeping with previous observations that high levels of plasma ACE correlate with structural changes in the arterial wall, such as the increase in carotid intima-media thickness 85 and its extent. 86

A significantly increased rate of binary restenosis (≥50% diameter stenosis at 6-month follow-up angiography) after stent implantation was also found in a series of 593 patients by Ribichini et al 26, 87 ; the rate was 33.9% in patients with the DD genotype, compared with 16.3% in ID patients and only 2.9% in II patients. The correlation between ACE genotype and the degree of intimal proliferation was also found in this series; the loss in minimal lumen diameter resulting from intrastent restenosis measured angiographically was 0.98 mm in patients with the DD genotype, 0.81 mm in ID patients, and 0.57 mm in II patients. 26, 87 Furthermore, the DD genotype appears to be associated not only with a markedly increased risk of intrastent restenosis, but also with poor long-term clinical outcome, because patients with the DD genotype more frequently have a diffuse type of neointimal proliferation that is more aggressive and more difficult to treat. 80, 87 The frequency of diffuse restenosis was found to be significantly associated with the D allele dose; 66% of all cases with diffuse restenosis were seen in patients with the DD genotype, compared with 32% in ID patients and 2% in II patients. 26, 87 This is a marked overrepresentation of the DD genotype in the patient group with diffuse poststent restenosis. The relative risk for diffuse restenosis is 2.5 (95% confidence interval 1.66–3.77) versus nonstenotic patients and 1.65 (95% confidence interval 1.19–2.27) versus patients with focal intrastent restenosis. 26, 87

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Re: ACE DD genotype and restenosis

Postby Anonymoose » Wed Dec 26, 2012 1:02 pm ... /1/16.full
5.4 Collagen accumulation and restenosis
The relationship between collagen accumulation and constrictive remodelling has been characterized by inconsistent results.40–43 Experimental angioplasty studies have shown associations between collagen accumulation and both expansive remodelling40,41 and constrictive remodelling.42–44 In a cryotherapy treated, balloon injury rabbit model, collagen content in all the arterial wall layers was correlated with constrictive remodelling.45

Stenting causes an even greater increase in collagen accumulation, in both arterial intima and media/adventitia layers compared with balloon angioplasty.5,15,16 This is likely due to extensive tissue damage and persistent circumferential stretching, both well-recognized stimuli for enhanced collagen synthesis.5,46

9.5 Aldosterone antagonism
Systemic and locally produced aldosterone modulates arterial structure through interactions with vascular aldosterone receptors.122 Aldosterone increases collagen synthesis in vitro123 and promotes collagen accumulation and fibrosis in the arterial wall.124 Non-selective (e.g. spironolactone) and selective aldosterone receptor antagonists (e.g. eplerenone) inhibit restenosis after experimental angioplasty by preventing collagen accumulation.125,126

If you go to the link above, there are means other than aldosterone block to prevent restenosis. Eplerenone is just my favorite because it (hopefully) stops aldosterone's other contributions to MS symptoms.
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