Clinical and pharmacogenetic impact of endothelial nitric oxide synthase polymorphisms on cardiovascular diseases

Nitric oxide (NO) is a vasoactive substance synthesized from l-arginine by neuronal (NOS1), endothelial (NOS3), and inducible (NOS2) nitric oxide synthases. NOS3 is the most important NO synthase isoform in the vascular endothelium and therefore it exerts critical roles in the cardiovascular system....

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Published inNitric oxide Vol. 63; pp. 39 - 51
Main Authors Oliveira-Paula, Gustavo H., Lacchini, Riccardo, Tanus-Santos, Jose E.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 28.02.2017
Subjects
Cardiovascular Diseases - genetics
Endothelial nitric oxide synthase
Genetic polymorphisms
Haplotypes
Humans
Nitric oxide
Nitric Oxide Synthase Type III - genetics
NOS3 gene
Pharmacogenetics
Pharmacogenomic Variants
Polymorphism, Genetic
Haplotypes
Endothelial nitric oxide synthase
NOS3 gene
Pharmacogenetics
Nitric oxide
Genetic polymorphisms
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Abstract Nitric oxide (NO) is a vasoactive substance synthesized from l-arginine by neuronal (NOS1), endothelial (NOS3), and inducible (NOS2) nitric oxide synthases. NOS3 is the most important NO synthase isoform in the vascular endothelium and therefore it exerts critical roles in the cardiovascular system. NOS3 is encoded by NOS3 gene, which displays a large number of genetic polymorphisms such as single nucleotide polymorphisms (SNPs), variable number of tandem repeats (VNTRs), microsatellites, and insertions/deletions. Interestingly, NOS3 regulation and NO production are affected by some NOS3 polymorphisms. Given these functional consequences and the protective role of NOS3 against cardiovascular diseases, many studies have investigated whether NOS3 polymorphisms affect the susceptibility to cardiovascular diseases and the responses to drugs that affect NOS3 activity in the cardiovascular system. In addition, a growing body of evidence shows the effects of combinations of NOS3 polymorphisms within haplotype blocks on NO bioavailability and disease susceptibility. In this review, we discuss the basic biochemical mechanisms of NOS3 regulation and the clinical and pharmacogenetic impact of NOS3 polymorphisms on cardiovascular diseases. [Display omitted] •Endothelial nitric oxide synthase plays a critical role in the cardiovascular system.•Genetic polymorphisms in the gene encoding this enzyme modify NO production.•These functional genetic polymorphisms affect the susceptibility to diseases.•They also affect the responses to cardiovascular drugs.•This review focused on basic biochemical mechanisms explaining those effects.
AbstractList Nitric oxide (NO) is a vasoactive substance synthesized from l-arginine by neuronal (NOS1), endothelial (NOS3), and inducible (NOS2) nitric oxide synthases. NOS3 is the most important NO synthase isoform in the vascular endothelium and therefore it exerts critical roles in the cardiovascular system. NOS3 is encoded by NOS3 gene, which displays a large number of genetic polymorphisms such as single nucleotide polymorphisms (SNPs), variable number of tandem repeats (VNTRs), microsatellites, and insertions/deletions. Interestingly, NOS3 regulation and NO production are affected by some NOS3 polymorphisms. Given these functional consequences and the protective role of NOS3 against cardiovascular diseases, many studies have investigated whether NOS3 polymorphisms affect the susceptibility to cardiovascular diseases and the responses to drugs that affect NOS3 activity in the cardiovascular system. In addition, a growing body of evidence shows the effects of combinations of NOS3 polymorphisms within haplotype blocks on NO bioavailability and disease susceptibility. In this review, we discuss the basic biochemical mechanisms of NOS3 regulation and the clinical and pharmacogenetic impact of NOS3 polymorphisms on cardiovascular diseases.
Nitric oxide (NO) is a vasoactive substance synthesized from l-arginine by neuronal (NOS1), endothelial (NOS3), and inducible (NOS2) nitric oxide synthases. NOS3 is the most important NO synthase isoform in the vascular endothelium and therefore it exerts critical roles in the cardiovascular system. NOS3 is encoded by NOS3 gene, which displays a large number of genetic polymorphisms such as single nucleotide polymorphisms (SNPs), variable number of tandem repeats (VNTRs), microsatellites, and insertions/deletions. Interestingly, NOS3 regulation and NO production are affected by some NOS3 polymorphisms. Given these functional consequences and the protective role of NOS3 against cardiovascular diseases, many studies have investigated whether NOS3 polymorphisms affect the susceptibility to cardiovascular diseases and the responses to drugs that affect NOS3 activity in the cardiovascular system. In addition, a growing body of evidence shows the effects of combinations of NOS3 polymorphisms within haplotype blocks on NO bioavailability and disease susceptibility. In this review, we discuss the basic biochemical mechanisms of NOS3 regulation and the clinical and pharmacogenetic impact of NOS3 polymorphisms on cardiovascular diseases. [Display omitted] •Endothelial nitric oxide synthase plays a critical role in the cardiovascular system.•Genetic polymorphisms in the gene encoding this enzyme modify NO production.•These functional genetic polymorphisms affect the susceptibility to diseases.•They also affect the responses to cardiovascular drugs.•This review focused on basic biochemical mechanisms explaining those effects.
Author Oliveira-Paula, Gustavo H.
Lacchini, Riccardo
Tanus-Santos, Jose E.
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  givenname: Riccardo
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  fullname: Tanus-Santos, Jose E.
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  organization: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil
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Keywords Haplotypes
Endothelial nitric oxide synthase
NOS3 gene
Pharmacogenetics
Nitric oxide
Genetic polymorphisms
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Snippet Nitric oxide (NO) is a vasoactive substance synthesized from l-arginine by neuronal (NOS1), endothelial (NOS3), and inducible (NOS2) nitric oxide synthases....
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SubjectTerms Cardiovascular Diseases - genetics
Endothelial nitric oxide synthase
Genetic polymorphisms
Haplotypes
Humans
Nitric oxide
Nitric Oxide Synthase Type III - genetics
NOS3 gene
Pharmacogenetics
Pharmacogenomic Variants
Polymorphism, Genetic
Title Clinical and pharmacogenetic impact of endothelial nitric oxide synthase polymorphisms on cardiovascular diseases
URI https://dx.doi.org/10.1016/j.niox.2016.08.004
https://www.ncbi.nlm.nih.gov/pubmed/27569446
https://www.proquest.com/docview/1835503188
Volume 63
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