Pro-Inflammatory Genetic Markers of Atherosclerosis

Abstract

Atherosclerosis (AS) is a chronic, progressive, multifactorial disease mostly affecting large and medium-sized elastic and muscular arteries. It has formerly been considered a bland lipid storage disease. Currently, multiple independent pathways of evidence suggest this pathological condition is a peculiar form of inflammation, triggered by cholesterol-rich lipoproteins and influenced both by environmental and genetic factors. The Human Genome Project opened up the opportunity to dissect complex human traits and to understand basic pathways of multifactorial diseases such as AS. Population-based association studies have emerged as powerful tools for examining genes with a role in common multifactorial diseases that have a strong environmental component. These association studies often estimate the risk of developing a certain disease in carriers and non-carriers of a particular genetic polymorphism. Dissecting out the influence of pro-inflammatory genes within the complex pathophysiology of AS and its complications will help to provide a more complete risk assessment and complement known classical cardiovascular risk factors. The detection of a risk profile will potentially allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug or lifestyle modification; i.e. it will open the door to personalized medicine.

Are the leukocyte telomere length attrition and telomerase activity alteration potential predictor biomarkers for sporadic TAA in aged individuals?

“…It was also associated with an increased systemic and local inflammation and aorta histopathological abnormalities. On the other hand, an increasing number of studies underlines the involvement of this signaling pathway in several CVDs (Balistreri et al 2004(Balistreri et al , 2009(Balistreri et al , 2013bFrantz et al 2007;Ionita et al 2010;Hofmann et al 2011;Navi et al 2013;Incalcaterra et al 2013). Its role in age-related aorta dysfunction and the aneurysm formation and related complications (dissection or rupture) recently is emerging (Pryshchep et al 2008;Eissler et al 2011;Li et al 2011;Song et al 2012;González-Ramos et al 2013;Navi et al 2013;Ruvolo et al 2014).…”

“…Their major number is prevalently associated with inflammation (such as genes related to TLR4-mediated signaling pathway) and stem cell biology (i.e., that of endothelial progenitor cells). Only a minority of implicated CVD-genes are linked to lipid and other classical risk factor pathways (Incalcaterra et al 2013). This underlines the crucial influence of inflammation on the rate of biological vascular ageing and its complications, such as vascular remodeling and medial degeneration, the typical pathological entities of several aorta diseases, including sporadic TAA.…”

“…This underlines the crucial influence of inflammation on the rate of biological vascular ageing and its complications, such as vascular remodeling and medial degeneration, the typical pathological entities of several aorta diseases, including sporadic TAA. Among the genes able to modulate inflammation, genes related to TLR4-mediated signaling pathway have been associated with the susceptibility for several CVDs (Balistreri et al 2004(Balistreri et al , 2009(Balistreri et al , 2013bFrantz et al 2007;Ionita et al 2010;Hofmann et al 2011;Navi et al 2013;Incalcaterra et al 2013). In our recent study (Ruvolo et al 2014), we have also demonstrated their role in sporadic TAA.…”

Mediterranean Diet and Healthy Ageing: A Sicilian Perspective

“…Previous studies have shown that the Sicilian male longevity is associated with an efficient genetic control of inflammatory responses [13]. Since the genetic structure of the average Sicilian population is very homogeneous and in Hardy-Weinberg equilibrium, the explanation for these data probably lies in the environmental characteristics of the zone in question, taking into account the gene environment interaction [8,9,12,13]. …”

Cyclin-dependent kinase 9 may as a novel target in downregulating the atherosclerosis inflammation (Review)

“…Genes coding for inflammatory or anti-inflammatory molecules are considered potentially ideal candidates for estimating the risk of developing atherosclerosis (5)(6)(7). Accordingly, the production of high inflammatory molecules has been associated with atherosclerosis (8)(9)(10)(11).…”