22 Citazioni (Scopus)

Abstract

Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). However, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. Cyclo-oxygenases (COXs) and 5-lipoxygenase (5-LO) are the key enzymes in the conversion of arachidonic acid to prostaglandins (PG) and leukotrienes (LT) and are implicated in a wide variety of inflammatory disorders, including atherosclerosis. In fact, PGE2 activates Matrix Metallo-proteinases whereas LTB4 is a chemoactractant for monocytes and activates gene expression in inflammatory cells. We have tested the hypothesis that anti-inflammatory variants of these genes confer genetic resistance to MI and conversely favour longevity. So, we analyzed MI patients, age-related controls and centenarians. The pro-inflammatory alleles of COX-2 and 5-LO were overrepresented in MI and under-represented in centenarians whereas age-related controls displayed intermediate values. MI is a multifactorial disease, hence MI might be the result of a cumulative effect which contributes with different timing to achieve a threshold where the chance to develop the diseases is very high. In particular, differences in inflammatory status can contribute to the chance of developing a risk phenotype. However, these studies might contribute to the determination of a risk profile which may allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug
Lingua originaleEnglish
pagine (da-a)2678-2685
Numero di pagine8
RivistaCurrent Pharmaceutical Design
Volume14
Stato di pubblicazionePublished - 2008

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Pharmacogenetics
Myocardial Infarction
Genes
Arachidonate 5-Lipoxygenase
Prostaglandin-Endoperoxide Synthases
Coronary Disease
Leukotriene B4
Leukotrienes
Dinoprostone
Arachidonic Acid
Pharmaceutical Preparations
Prostaglandins
Monocytes
Atherosclerosis
Peptide Hydrolases
Anti-Inflammatory Agents
Alleles
Inflammation
Phenotype
Gene Expression

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Pharmacology

Cita questo

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title = "Pro-inflammatory gene variants in myocardial infarction and longevity: implications for pharmacogenomics.",
abstract = "Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). However, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. Cyclo-oxygenases (COXs) and 5-lipoxygenase (5-LO) are the key enzymes in the conversion of arachidonic acid to prostaglandins (PG) and leukotrienes (LT) and are implicated in a wide variety of inflammatory disorders, including atherosclerosis. In fact, PGE2 activates Matrix Metallo-proteinases whereas LTB4 is a chemoactractant for monocytes and activates gene expression in inflammatory cells. We have tested the hypothesis that anti-inflammatory variants of these genes confer genetic resistance to MI and conversely favour longevity. So, we analyzed MI patients, age-related controls and centenarians. The pro-inflammatory alleles of COX-2 and 5-LO were overrepresented in MI and under-represented in centenarians whereas age-related controls displayed intermediate values. MI is a multifactorial disease, hence MI might be the result of a cumulative effect which contributes with different timing to achieve a threshold where the chance to develop the diseases is very high. In particular, differences in inflammatory status can contribute to the chance of developing a risk phenotype. However, these studies might contribute to the determination of a risk profile which may allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug",
keywords = "IMMUNOGENETICS,INFARCTION,INFLAMMATION,LONGEVITY,PHARMACOGENOMICS",
author = "Gregorio Caimi and Calogero Caruso and Enrico Hoffmann and Giuseppina Candore and Valeria Scafidi and Egle Incalcaterra and Balistreri, {Carmela Rita} and Sonya Vasto and Valeria Scafidi",
year = "2008",
language = "English",
volume = "14",
pages = "2678--2685",
journal = "Current Pharmaceutical Design",
issn = "1381-6128",
publisher = "Bentham Science Publishers B.V.",

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TY - JOUR

T1 - Pro-inflammatory gene variants in myocardial infarction and longevity: implications for pharmacogenomics.

AU - Caimi, Gregorio

AU - Caruso, Calogero

AU - Hoffmann, Enrico

AU - Candore, Giuseppina

AU - Scafidi, Valeria

AU - Incalcaterra, Egle

AU - Balistreri, Carmela Rita

AU - Vasto, Sonya

AU - Scafidi, Valeria

PY - 2008

Y1 - 2008

N2 - Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). However, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. Cyclo-oxygenases (COXs) and 5-lipoxygenase (5-LO) are the key enzymes in the conversion of arachidonic acid to prostaglandins (PG) and leukotrienes (LT) and are implicated in a wide variety of inflammatory disorders, including atherosclerosis. In fact, PGE2 activates Matrix Metallo-proteinases whereas LTB4 is a chemoactractant for monocytes and activates gene expression in inflammatory cells. We have tested the hypothesis that anti-inflammatory variants of these genes confer genetic resistance to MI and conversely favour longevity. So, we analyzed MI patients, age-related controls and centenarians. The pro-inflammatory alleles of COX-2 and 5-LO were overrepresented in MI and under-represented in centenarians whereas age-related controls displayed intermediate values. MI is a multifactorial disease, hence MI might be the result of a cumulative effect which contributes with different timing to achieve a threshold where the chance to develop the diseases is very high. In particular, differences in inflammatory status can contribute to the chance of developing a risk phenotype. However, these studies might contribute to the determination of a risk profile which may allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug

AB - Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). However, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. Cyclo-oxygenases (COXs) and 5-lipoxygenase (5-LO) are the key enzymes in the conversion of arachidonic acid to prostaglandins (PG) and leukotrienes (LT) and are implicated in a wide variety of inflammatory disorders, including atherosclerosis. In fact, PGE2 activates Matrix Metallo-proteinases whereas LTB4 is a chemoactractant for monocytes and activates gene expression in inflammatory cells. We have tested the hypothesis that anti-inflammatory variants of these genes confer genetic resistance to MI and conversely favour longevity. So, we analyzed MI patients, age-related controls and centenarians. The pro-inflammatory alleles of COX-2 and 5-LO were overrepresented in MI and under-represented in centenarians whereas age-related controls displayed intermediate values. MI is a multifactorial disease, hence MI might be the result of a cumulative effect which contributes with different timing to achieve a threshold where the chance to develop the diseases is very high. In particular, differences in inflammatory status can contribute to the chance of developing a risk phenotype. However, these studies might contribute to the determination of a risk profile which may allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug

KW - IMMUNOGENETICS,INFARCTION,INFLAMMATION,LONGEVITY,PHARMACOGENOMICS

UR - http://hdl.handle.net/10447/46627

M3 - Article

VL - 14

SP - 2678

EP - 2685

JO - Current Pharmaceutical Design

JF - Current Pharmaceutical Design

SN - 1381-6128

ER -