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Atherosclerosis Is an Inflammatory Disease which Lacks a Common Anti-inflammatory Therapy: How Human Genetics Can Help to This Issue. A Narrative Review

Atherosclerosis is a multifactorial disease triggered and sustained by different risk factors such as dyslipidemia, arterial hypertension, diabetes mellitus, smoke, etc. Since a couple of decades, a pivotal role for inflammation in its pathogenesis has been recognized and proved at molecular levels,...

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Autores principales: Fava, Cristiano, Montagnana, Martina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808208/
https://www.ncbi.nlm.nih.gov/pubmed/29467655
http://dx.doi.org/10.3389/fphar.2018.00055
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author Fava, Cristiano
Montagnana, Martina
author_facet Fava, Cristiano
Montagnana, Martina
author_sort Fava, Cristiano
collection PubMed
description Atherosclerosis is a multifactorial disease triggered and sustained by different risk factors such as dyslipidemia, arterial hypertension, diabetes mellitus, smoke, etc. Since a couple of decades, a pivotal role for inflammation in its pathogenesis has been recognized and proved at molecular levels, and already described in many animal models. Despite all this knowledge, due to the complexity of the specific inflammatory process subtending atherosclerosis and to the fact that inflammation is also a protective response against microorganisms, no anti-inflammatory therapy has been rendered available in the therapeutic armamentarium against atherosclerosis and vascular events till 2017 when canakinumab in the first ad-hoc randomized clinical trial (RCT) proved for the first time that targeting specifically inflammation lowers cardiovascular (CV) events. From the genetic side, in the 90's and early 2000, several genetic markers in inflammatory pathway have been explored searching for an association with athero-thrombosis which gave seldom consistent results. Then, in the genomic era, plenty of genetic markers covering most of the genome have been analyzed at once without a priori information. The results coming from genome wide association studies (GWAS) have pinpointed some loci closed to inflammatory molecules consistently associated with atherosclerosis and CV consequences revamping the strict link between inflammation and atherosclerosis and suggesting some tailored target therapy. Whole-exome and whole-genome sequencing will come soon showing new and old loci associated with atherosclerosis suggesting new molecular targets or underlying which inflammatory pathway could be most attractive to target for blocking atherosclerosis even in its early stages.
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spelling pubmed-58082082018-02-21 Atherosclerosis Is an Inflammatory Disease which Lacks a Common Anti-inflammatory Therapy: How Human Genetics Can Help to This Issue. A Narrative Review Fava, Cristiano Montagnana, Martina Front Pharmacol Pharmacology Atherosclerosis is a multifactorial disease triggered and sustained by different risk factors such as dyslipidemia, arterial hypertension, diabetes mellitus, smoke, etc. Since a couple of decades, a pivotal role for inflammation in its pathogenesis has been recognized and proved at molecular levels, and already described in many animal models. Despite all this knowledge, due to the complexity of the specific inflammatory process subtending atherosclerosis and to the fact that inflammation is also a protective response against microorganisms, no anti-inflammatory therapy has been rendered available in the therapeutic armamentarium against atherosclerosis and vascular events till 2017 when canakinumab in the first ad-hoc randomized clinical trial (RCT) proved for the first time that targeting specifically inflammation lowers cardiovascular (CV) events. From the genetic side, in the 90's and early 2000, several genetic markers in inflammatory pathway have been explored searching for an association with athero-thrombosis which gave seldom consistent results. Then, in the genomic era, plenty of genetic markers covering most of the genome have been analyzed at once without a priori information. The results coming from genome wide association studies (GWAS) have pinpointed some loci closed to inflammatory molecules consistently associated with atherosclerosis and CV consequences revamping the strict link between inflammation and atherosclerosis and suggesting some tailored target therapy. Whole-exome and whole-genome sequencing will come soon showing new and old loci associated with atherosclerosis suggesting new molecular targets or underlying which inflammatory pathway could be most attractive to target for blocking atherosclerosis even in its early stages. Frontiers Media S.A. 2018-02-06 /pmc/articles/PMC5808208/ /pubmed/29467655 http://dx.doi.org/10.3389/fphar.2018.00055 Text en Copyright © 2018 Fava and Montagnana. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Fava, Cristiano
Montagnana, Martina
Atherosclerosis Is an Inflammatory Disease which Lacks a Common Anti-inflammatory Therapy: How Human Genetics Can Help to This Issue. A Narrative Review
title Atherosclerosis Is an Inflammatory Disease which Lacks a Common Anti-inflammatory Therapy: How Human Genetics Can Help to This Issue. A Narrative Review
title_full Atherosclerosis Is an Inflammatory Disease which Lacks a Common Anti-inflammatory Therapy: How Human Genetics Can Help to This Issue. A Narrative Review
title_fullStr Atherosclerosis Is an Inflammatory Disease which Lacks a Common Anti-inflammatory Therapy: How Human Genetics Can Help to This Issue. A Narrative Review
title_full_unstemmed Atherosclerosis Is an Inflammatory Disease which Lacks a Common Anti-inflammatory Therapy: How Human Genetics Can Help to This Issue. A Narrative Review
title_short Atherosclerosis Is an Inflammatory Disease which Lacks a Common Anti-inflammatory Therapy: How Human Genetics Can Help to This Issue. A Narrative Review
title_sort atherosclerosis is an inflammatory disease which lacks a common anti-inflammatory therapy: how human genetics can help to this issue. a narrative review
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808208/
https://www.ncbi.nlm.nih.gov/pubmed/29467655
http://dx.doi.org/10.3389/fphar.2018.00055
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