Risk factors in coronary atherosclerosis athero-inflammation: the meeting point

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...

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Development and validation of a high-performance liquid chromatography–electrospray mass spectrometry method for the simultaneous determination of 23 eicosanoids

“…The cardinal features of inflammation (heat, pain, redness, and swelling) are caused in large part by an increase in blood flow and vascular permeability and the ability for larger inflammatory mediators to cross the endothe- utilized to more accurately predict future CVD risk. Promising results have been shown using protein biomarkers including Creactive protein (CRP), fibrinogen, and cytokines such as tumor necrosis factor-␣ (TNF-␣) and some of the interleukins IL-1 and IL-6 [6,8,12,13].…”

“…Eicosanoids are the biological oxidative metabolites of arachidonic acid (eicosatetraenoic acid, AA), responsible for a large variety of physiological functions including regulating inflammation. AA is a 20-carbon -6 polyunsaturated fatty acid (PUFA) with four unsaturated double bonds (all cis) at positions 5,8,11, and 14 ( Fig. 1).…”

Molecular Targets of Antihypertensive Peptides: Understanding the Mechanisms of Action Based on the Pathophysiology of Hypertension

“…Hypertension rarely presents with early symptoms, and even if diagnosed early, it is often treated inadequately [ 3 , 4 ]. Nevertheless, hypertension is a significant risk factor for atherosclerosis and hence predisposes to coronary heart disease, cerebrovascular disease, and renal disease [ 5 , 6 , 7 , 8 , 9 ]. In addition to tremendous health burden, treatment and prevention of hypertension are also associated with substantial socioeconomic consequences.…”