Relationship between endothelial nitric oxide synthase (eNOS) and natural history of intracranial aneurysms: meta-analysis

Abstract

The aneurysmal subarachnoid hemorrhage is a major public health problem described as a sudden drastic event with no warning symptoms and high morbidity and mortality rates. The role of the endothelial isoform of nitric oxide synthase gene polymorphism in intracranial aneurysms (IAs) is still a matter of controversy with divergent findings among European, American, and Asian populations. Our study purposed to test the association between intracranial aneurysms formation and nitric oxide gene polymorphisms through a systematic review and meta-analysis. Systematic search on Medline, Lilacs, and EMBASE was performed. The primary search resulted in 139 papers, out of which 9 met our inclusion criteria after a full text analysis. The dominant T786C model found a significant association with IA (OR 1.22, 95 % CI 1.04-1.44, p = 0.01), so did studies of the recessive T786C model (OR 0.37, 95 % CI 0.30-0.45, p < 0.0001) but with opposite effect. Our findings support the presence of the T786C polymorphism as a predictor for the development of intracranial aneurysm in the cerebral vascular system. More studies are necessary in order to elucidate the pathways of the endothelial nitric oxide synthase (eNOS) in cerebrovascular diseases and in defining how different allelic combinations of the eNOS gene single-nucleotide polymorphism (SNP) could favor this pathological process.

Tissue-specific relaxin-2 is differentially associated with the presence/size of an arterial aneurysm and the severity of atherosclerotic disease in humans

“…Endothelial cells express eNOS to serve as an important source of NO, a potent vasodilator and inhibitor of inflammation, platelet aggregation, and smooth muscle cell proliferation [ 42 ]. Interestingly, eNOS gene polymorphisms have been associated with vascular diseases [ 43 ]; two recent meta-analyses have identified the T786C polymorphism of eNOS as a predictor for the development of intracranial aneurysms in the cerebral vascular system [ 44 , 45 ], and various polymorphisms of eNOS have been linked to AAA [ 46 – 48 ]. Our findings of increased eNOS levels in larger aneurysms are in accordance with a recent animal study [ 49 ], in which increased eNOS activity reduced smooth muscle α-actin and upregulated MMPs during flow-induced intracranial aneurysm formation.…”

Genetic basis of intracranial aneurysm formation and rupture: clinical implications in the postgenomic era

“…9,63 Complementary studies of variants have also identified the presence of aneurysms as well as subsets of patients with aneurysms that are more likely to rupture, including tandem repeats in endothelial nitric oxide synthase (eNOS/NOS3) polymorphisms, with an OR as high as 11.4 (95% CI 1.7-75.9, p = 0.004) for individuals harboring 3 distinct variant alleles in this gene. 30,31,52 Further studies of eNOS polymorphic variants have suggested an association between rs2070744 and DCI following aSAH; however, these results only reached borderline significance (OR 2.936, 95% CI 1.048-8.226; p = 0.040). 24 Data from the same group also implicates a variant in HMGB1 in DCI (rs2249825: OR 5.695, 95% CI 1.804-17.975; p = 0.003).…”

The vascular protective role of oestradiol: a focus on postmenopausal oestradiol deficiency and aneurysmal subarachnoid haemorrhage

“…NOS‐3 knockout predisposed mice subjected to unilateral carotid artery ligation to the formation of intracranial aneurysms (Abruzzo et al ., ). Single nucleotide polymorphisms (SNPs) in the eNOS gene are associated with the risk of developing IA in several populations (Yang et al ., ; Paschoal et al ., ).…”