Promoter site fibrous

Fig. 2. Proposed process of arteriosclerosis leading to ischemic disease. It is proposed that arteriosclerosis is a process of inflammation within the arterial wall that is initiated by arterial injury (endothelial dysfunction), causing the trapping of lipoproteins (Rll, Zl). These undergo oxidation as proposed in Fig. 1, leading to foam cells saturated with lipid droplets. Continued accumulation of fatty material within the blood vessel wall promotes a fatty streak. Ultimately, there is muscle cell migration and fibrosis leading to a plaque that consists of a fibrous cap with cholesterol crystals and debris within the deep necrotic layer, while inflammatory cells form a dynamic outer edge. It is thought that oxidized lipoproteins can facilitate many of these processes. Mechanical forces predispose the soft outer layer of the plaque to rupture at sites of structural weakness. Rupture of plaques causes thrombosis and incorporation of thrombi into the plaque. Ultimately, a large thrombus appearing in an obstructed vessel can lead to sudden ischemia and unstable coronary syndromes.

Scar tissue formation is directly responsible for the diflFiculty and morbidity associated with lead extraction (14-16). The difficulty in extraction is further enhanced by the use of passive fixation devices, longer implant durations, and the greater number of leads implanted in any given patient. The passive fixation devices promoted exuberant encapsulating fibrous scar formation at the myocardial electrode interface (Fig. 6.2). Scar tissue forms at the contact sites along vascular walls and, in the case of multiple electrodes, scarring can completely encompass multiple leads. In extreme cases, the scar tissue may completely obliterate the venous channel. One of the most common locations of scar formation is at the lead venous entry site. Leads implanted more than 8 years are the most difficult to remove. 

Inspired by a-helices in nature and their ability to self-assemble into oligomeric coiled coils, a number of researchers have tailored helical peptides in order to generate fibrous structures. As an example, Woolfson and coworkers ° described the design of a single-peptide, based on an a-helical coiled-coil motif, named MagicWand, which self-assembled into extended and thickened nano-to mesoscale fibers of high stability and order. The peptide had a heptad sequence repeat, abcdefg, with isoleucine and leucine residues at the a and d sites to promote dimerization. 

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