Inflammation In Atherosclerotic Diseases

Recent studies have identified systemic inflammatory markers such as elevated CRP as a predictor of increased morbidity and mortality from atherosclerotic disease. The rupture of the surface of atherosclerotic plaque, giving rise to superimposed thrombosis and arterial occlusion, is now considered the most frequent primary cause for acute coronary syndromes such as unstable angina, myocardial infarction, and sudden cardiac death. The atheroma’s vulnerability to rupture is correlated with a cellular infiltrate of macrophages and activated T cells in the plaque tissue. Researchers in the Lowance Center for Human Immunology investigate immune abnormalities in patients with myocardial infarction. Molecular pathways underlying the tissue-damaging effects of immune cells in atherosclerotic plaques are explored with the ultimate goal of developing new therapeutic strategies.

Publications

Goronzy JJ, Weyand CM. Immunosuppression in atherosclerosis: Mobilizing the opposition within. Circulation 114:1901-1904, 2006.

Niessner A, Sato K, Chaikof E, Colmegna I, Goronzy JJ, Weyand CM. Pathogen-sensing plasmacytoid dendritic cells stimulate cytotoxic T-cell function in the atherosclerotic plaque through interferon-α. Circulation 114:2482-2489, 2006.

Pryshchep S, Sato K, Goronzy JJ, Weyand CM. T cell recognition and killing of vascular smooth muscle cells in acute coronary syndrome. Circ Res 98:1168-1176, 2006.

Sato K, Niessner A, Kopecky SL, Frye RL, Goronzy JJ, Weyand CM. TRAIL-expressing T cells induce apoptosis of vascular smooth muscle cells in the atherosclerotic plaque. J Exp Med 203:239-250, 2006 .

Zhang X , Niessner A, Nakajima T, Ma-Krupa W, Kopecky SL, Frye RL, Goronzy JJ, Weyand CM. IL-12 induced CCR5-mediated T-cell recruitment to the atherosclerotic regulates tissue invasiveness of plaque-infiltrating T cells in acute coronary syndrome. Circ Res 98:524-531, 2006.

Warrington KJ, Kent PD, Frye RL, Lymp JF, Kopecky SL, Goronzy JJ, Weyand CM. Rheumatoid arthritis is an independent risk factor for multi-vessel coronary artery disease: a case control study. Arthritis Res Ther 7:R984-R991, 2005.

Nakajima T, Goek O, Kopecky SL, Frye RL, Goronzy JJ, Weyand CM. De novo expression of killer immunoglobulin-like receptors and signaling proteins regulates the cytotoxic function of CD4 T cells in acute coronary syndromes. Circ Res 93:106-113, 2003.

Nakajima T, Schulte S, Warrington KJ, Kopecky SL, Frye RL, Goronzy JJ, Weyand CM. T-cell-mediated lysis of endothelial cells in acute coronary syndromes. Circulation 105:570-575, 2002.

Liuzzo G, Vallejo AN, Kopecky SL, Frye RL, Holmes DR, Goronzy JJ, Weyand CM. Molecular fingerprint of interferon-γ signaling in unstable angina. Circulation 103:1509-1514, 2001.

Weyand CM, Goronzy JJ, Liuzzo G, Kopecky SL, Holmes DR, Frye RL. T-cell immunity in acute coronary syndromes. Mayo Clin Proc 76:1011-1020, 2001.

Liuzzo G, Goronzy JJ, Yang H, Kopecky SL, Holmes DR, Frye RL, Weyand CM. Monoclonal T cell proliferation and plaque instability in acute coronary syndromes. Circulation 101:2883-2888, 2000.

Liuzzo G, Kopecky SL, Frye RL, Maseri A, Goronzy JJ, Weyand CM. Perturbation of the T cell repertoire in patients with unstable angina. Circulation 100:2135-2139, 1999.