Imaging of the unstable plaque

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

“…Atherosclerosis is a progressive (and inflammatory ) disease (Altman 2003; Binder et al 2002; Blake and Ridker 2001; Duewell et al 2010; Dwyer et al 2004; Forrester 2002, 2004; Gieseg et al 2009; Grainger 2007; Hansson 2001, 2005; Himmelfarb et al 2002; Kibel et al 2008; Kunsch and Medford 1999; Libby 2002; Libby et al 2002; Madamanchi et al 2005a, b; Mullenix et al 2005; Nigro et al 2006; Packard and Libby 2008; Paoletti et al 2004; Popa et al 2007; Rader and Daugherty 2008; Ridker et alet al 2004; Ross 1999; Schleicher and Friess 2007; Subramanian and Ferrante 2009; Sullivan 2009; Tan and Lip 2008; Tang et al 2009; Taqueti et al 2006; Tedgui and Mallat 2006; van Leuven et al 2008; van Oostrom et al 2004; Willerson and Ridker 2004; Young et al 2002) characterized by the accumulation of both oxidised lipids and various fibrous elements in arteries, often as plaques (Lusis 2000; Stocker and Keaney 2004). Several lines of evidence point to the involvement of iron in these processes:

Both iron and oxidised lipids (de Valk and Marx 1999; Smith et al 1992) are found in atherosclerotic lesions (Altamura and Muckenthaler 2009; Brewer 2007; Chau 2000; Fernandes de Godoy et al 2007; Gajda et al 2008; Halliwell 2009; Horwitz et al 1998; Kazi et al 2008; Lee et al 1998; McRae et al 2009; Rajendran et al 2007; Ramakrishna et al 2003; Roijers et al 2005; Smith et al 1992; Stadler et al 2004; Stanley et al 2006; Stocker and Keaney 2005; Sullivan 2009; Watt et al 2006; Wolff et al 2004; Yuan and Li 2008)

Iron depletion by dietary or other means delays the formation of such lesions...

…”

Genetic Regulation of Endothelial Inflammatory Responses in Baboons

“…In estimating heritability, we first adjusted each raw trait for a covariate set of age, sex, and body weight, regardless of their significance for that trait, and then normalized and standardized the covariate-adjusted residual prior to statistical genetic analysis. Heritability, h2, was estimated as the proportion of residual variance explained by pedigree relationships (i.e., h2 = σ2 G /sigma2 P , where σ2 G represents the additive genetic, and α2 P the residual phenotypic, variances); significance was assessed by comparison with a model in which heritability was fixed at zero. Simulations, using the same pedigree and data (i.e., lysate protein levels) structure as in this study demonstrated we had 80% power to detect h2=0.21 as significantly different from zero (at α=0.05; M.C.Mahaney, unpublished observations).…”

“…Heritability, h2, was estimated as the proportion of residual variance explained by pedigree relationships (i.e., h2 = σ2 G /sigma2 P , where σ2 G represents the additive genetic, and α2 P the residual phenotypic, variances); significance was assessed by comparison with a model in which heritability was fixed at zero. Simulations, using the same pedigree and data (i.e., lysate protein levels) structure as in this study demonstrated we had 80% power to detect h2=0.21 as significantly different from zero (at α=0.05; M.C.Mahaney, unpublished observations). Bivariate models were used to estimate correlation coefficients for the endothelial cell traits with various metabolic traits, and significance of the correlation was assessed by comparison with a model in which the traits were forced to be uncorrelated.…”

“…The expressions of E-selectin, ICAM-1 and VCAM-1 were increased 12.2-, 41.4- and 3.5-fold, respectively (p<0.0001). The quantitative levels of several traits were heritable after TNF-α stimulation: h2=0.244 ( P =0.017) for IL-8 and h2=0.278 ( P =0.0028) for E-selectin in culture medium, h2=0.207 ( P =0.034) for ICAM-1; and h2=0.369 ( P =0.00015) for VCAM-1 expression on EC surfaces. Furthermore, a significant heritability was observed for lysate protein level, which is a measure of cell growth rate, with (h2=0.639, P =0.00021) or without (h2=0.511, P =0.00069) TNF-α stimulation.…”

Intravascular Thermography for Assessing Vulnerable Plaques

“…Current knowledge of coronary artery disease progression has significantly evolved and the interest has been focused on the development of new imaging techniques for the early detection of vulnerable lesions, which are ultimately responsible for the majority of acute cardiovascular events [2,3].…”