Response to Letter Regarding Article, “Expression of Heat Shock Protein 27 in Human Atherosclerotic Plaques and Increased Plasma Level of Heat Shock Protein 27 in Patients With Acute Coronary Syndrome”
We are grateful to Drs Rose and Dunn for raising interesting questions in response to our article.1 In the atherosclerotic plaque core area, healthy smooth-muscle cells become scarce and are replaced by macrophages and foam cells. As the atherosclerosis progress, cells initially may express proteins involved in the cell survival, but in the later stages, mechanisms involved in cell death may dominate.
We hypothesize that in the process of smooth-muscle-cell death, heat shock protein 27 (Hsp27) expression will be increased initially by noxious stress such as oxidative stress to save the cells from death. However, as healthy smooth-muscle cells die and macrophages and foam cells populate and secrete proteases, Hsp27 expression will be decreased, and cell death mechanisms will dominate over cell survival.2 The lower expression of Hsp27 will facilitate further cell death and decreased cellularity.
The finding of increased expression of phosphorylated Hsp27 in the nearby normal-looking area compared with the reference internal mammary arteries may represent the earlier stages of atherosclerosis, in which Hsp27 is still functioning to save the cells from death. As atherosclerosis progresses with decreased cellularity, decreased expression of Hsp27 and the unfavorable environment of cell survival are probably intimately associated. What we see in the plaque core are the more advanced stages of atherosclerosis. Decreased expression of Hsp27 was also associated with cardiac allograft vasculopathy.3
Curiously, not every heat shock protein was decreased in the plaque core area. We especially were interested by the observation that Hsp70 expression was not significantly different between the plaque core area and the nearby normal-looking area.1 We are now studying how Hsp27 is involved in the prevention of atherosclerosis.
Park HK, Park EC, Bae SW, Park MY, Kim SW, Yoo HS, Tudev M, Ko YH, Choi YH, Kim S, Kim DI, Kim YW, Lee BB, Yoon JB, Park JE. Expression of heat shock protein 27 in human atherosclerotic plaques and increased plasma level of heat shock protein 27 in patients with acute coronary syndrome. Circulation. 2006; 114: 886–893.
Martin-Ventura JL, Nicolas V, Houard X, Blanco-Colio LM, Leclercq A, Egido J, Vranckx R, Michel JB, Meilhac O. Biological significance of decreased Hsp27 in human atherosclerosis. Arterioscler Thromb Vasc Biol. 2006; 26: 1337–1343.
De Souza AI, Wait R, Mitchell AG, Banner NR, Dunn MJ, Rose ML. Heat shock protein 27 is associated with freedom from graft vasculopathy after human cardiac transplantation. Circ Res. 2005; 97: 192–198.