Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes

<p>Abstract</p> <p>Background</p> <p>Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture.</p> <p>The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular matrix (ECM) of atherosclerotic plaques by cathepsin K mediated processes.</p> <p>Methods</p> <p>We 1) cultured human macrophages on ECM and measured cathepsin K generated fragments of type I collagen (C-terminal fragments of Type I collagen (CTX-I) 2) investigated the presence of CTX-I in human coronary arteries and 3) finally investigated the clinical potential by measuring circulating CTX-I in women with and without radiographic evidence of aortic calcified atherosclerosis.</p> <p>Results</p> <p>Immune-histochemistry of early and advanced lesions of coronary arteries demonstrated co-localization of Cathepsin-K and CTX-I in areas of intimal hyperplasia and in shoulder regions of advanced plaques. Treatment of human monocytes with M-CSF or M-CSF+LDL generated macrophages and foam cells producing CTX-I when cultured on type I collagen enriched matrix. Circulating levels of CTX-I were not significantly different in women with aortic calcifications compared to those without.</p> <p>Conclusions</p> <p>Human macrophage foam cells degrade the atherosclerotic plaques though cathepsin K mediated processes, resulting in increase in levels of CTX-I. Serum CTX-I was not elevated in women with aortic calcification, likely due to the contribution of CTX-I from osteoclastic bone resorption which involves Cathepsin-K. The human macrophage model system may be used to identify important pathway leading to excessive proteolytic plaque remodeling and plaque rupture.</p

Determination of Barrier Heights from Low‐Temperature Heat‐Capacity Data

A method is presented by which barrier heights, in potential functions hindering the internal rotation of methyl groups, or spectroscopically inactive vibrational frequencies, can be obtained solely from thermal data for the solid phase. The observed heat capacities are analyzed in terms of contributions from the lattice vibrations, the internal vibrations, the expansion of the lattice, and the internal rotation. At low temperatures, the hindered rotation can be treated as torsional oscillation with a frequency related to the barrier height. It is shown that barrier heights derived by this method are in accord with those estimated from comparison of gas‐phase entropies, but can be determined with greater precision than such values.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69463/2/JCPSA6-39-5-1227-1.pd