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

Abstract

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.

Keywords: DNA sequencing; anti-inflammatory drugs; atherosclerosis; genetics; genome wide association study; inflammation.