BADERC Welcome

Peter Libby, M.D.

Inflammation and Atherosclerosis

The links between the major theme of the Libby laboratory, inflammation in cardiovascular and metabolic diseases, and diabetes have become increasingly apparent over the last several years. Recent work has studied the effects of advanced glycation end product – derivatized proteins and lipoprotein on gene expression in cells involved in atherosclerosis. These studies have established new links between hyperglycemia and reverse cholesterol transport from macrophages and recruitment of macrophages to atherosclerotic lesions. Other recent work from Libby laboratory has explored the interface between adipose tissue and adaptive immunity. We showed that T cells regulate aspects of biology of adipose tissue. In particular we defined a role for the Th1 cytokine gamma interferon in regulating insulin sensitivity in obese mice. We have also shown that adiponectin can inhibit the recruitment of T cells to atherosclerotic plaques by modulating chemokine action. These studies have made use of proteomic and RNA profiling facilities available through BADERC

References:

Isoda K, Young J, Zirlik A, MacFarlane LA, Tsuboi N, Gerdes N, Schönbeck U, Libby P. Metformin inhibits proinflammatory responses and nuclear factor-kB in human vascular wall cells. Arterioscler Thromb Vasc Biol 2006;26:611-617.
Isoda K, Folco EJ, Shimizu K, Libby P. AGE-BSA decreases ABCG1 expression and reduces macrophage cholesterol efflux to HDL. Atherosclerosis 2007;192:298-304.
Isoda K, Folco E, Marwali MR, Ohsuzu F, Libby P. Glycated LDL increases monocyte CC chemokine receptor 2 expression and monocyte chemoattractant protein-1-mediated chemotaxis. Atherosclerosis 2008;198:307-312.
Zirlik A, Abdullah SM, Gerdes N, MacFarlane L, Schönbeck U, Khera A, McGuire DK, Vega GL, Grundy S, Libby P, de Lemos JA. Interleukin-18, the metabolic syndrome, and subclinical atherosclerosis. Results from the Dallas Heart Study. Arterioscler Thromb Vasc Biol. 2007;27:2043-2049.
Okamoto Y, Folco EJ, Minami M, Wara AK, Feinberg MW, Sukhova GK, Colvin RA, Kihara S, Funahashi T, Luster AD, Libby P. Adiponectin inhibits the production of CXCR3 chemokine ligands in macrophages and reduces T lymphocyte recruitment in atherogenesis. Circ Res 2008;102:218-225.
Rocha VZ, Folco EJ, Sukhova G, Shimizu K, Gotsman I, Vernon AH, Libby P. Interferon-gamma, a Th1 cytokine, regulates fat inflammation — a role for adaptive immunity in obesity. Circ Res 2008;103:467-476.
Medoff BD, Okamoto Y, Leyton P, Sandall B, Raher M, Kihara S, Bloch KD, Libby P, Luster AD. Adiponectin-deficiency increases allergic airway inflammation and pulmonary vascular remodeling. Am J Respir Cell Molec Biol 2009; in press.

Recent Reviews or Chapters:

Libby P, Nathan DM, Abraham K, Brunzell JD, Fradkin J, Haffner SM, Hsueh W, Rewers M, Roberts T, Savage P, Skarlatos S, Wassef M, Rabadan-Diehl C. Report of the National Heart, Lung, and Blood Institute-National Institute of Diabetes and Digestive and Kidney Diseases Working Group on Cardiovascular Complications of Type 1 Diabetes Mellitus. Circulation 2005;111:3489-3493.
Libby P, Plutzky J. Inflammation in diabetes mellitus: role of peroxisome proliferator-activated receptor–a and peroxisome proliferator-activated receptor–g agonists. Am J Cardiol 2007;99[suppl]:27B-40B.
Beckman JA, Libby P, Creager MA. Diabetes mellitus, the metabolic syndrome, and atherosclerotic vascular disease. In: Libby P, Bonow RO, Mann DL, Zipes DP, Braunwald E, editors. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 8th edition. Philadelphia: Elsevier Saunders;2007. p. 1093-1106.
Rocha VZ and Libby P. The multiple facets of the fat tissue. Thyroid 2008;18:175-183.






			Peter Libby, M.D. Inflammation and Atherosclerosis The links between the major theme of the Libby laboratory, inflammation in cardiovascular and metabolic diseases, and diabetes have become increasingly apparent over the last several years. Recent work has studied the effects of advanced glycation end product – derivatized proteins and lipoprotein on gene expression in cells involved in atherosclerosis. These studies have established new links between hyperglycemia and reverse cholesterol transport from macrophages and recruitment of macrophages to atherosclerotic lesions. Other recent work from Libby laboratory has explored the interface between adipose tissue and adaptive immunity. We showed that T cells regulate aspects of biology of adipose tissue. In particular we defined a role for the Th1 cytokine gamma interferon in regulating insulin sensitivity in obese mice. We have also shown that adiponectin can inhibit the recruitment of T cells to atherosclerotic plaques by modulating chemokine action. These studies have made use of proteomic and RNA profiling facilities available through BADERC References: Isoda K, Young J, Zirlik A, MacFarlane LA, Tsuboi N, Gerdes N, Schönbeck U, Libby P. Metformin inhibits proinflammatory responses and nuclear factor-kB in human vascular wall cells. Arterioscler Thromb Vasc Biol 2006;26:611-617. Isoda K, Folco EJ, Shimizu K, Libby P. AGE-BSA decreases ABCG1 expression and reduces macrophage cholesterol efflux to HDL. Atherosclerosis 2007;192:298-304. Isoda K, Folco E, Marwali MR, Ohsuzu F, Libby P. Glycated LDL increases monocyte CC chemokine receptor 2 expression and monocyte chemoattractant protein-1-mediated chemotaxis. Atherosclerosis 2008;198:307-312. Zirlik A, Abdullah SM, Gerdes N, MacFarlane L, Schönbeck U, Khera A, McGuire DK, Vega GL, Grundy S, Libby P, de Lemos JA. Interleukin-18, the metabolic syndrome, and subclinical atherosclerosis. Results from the Dallas Heart Study. Arterioscler Thromb Vasc Biol. 2007;27:2043-2049. Okamoto Y, Folco EJ, Minami M, Wara AK, Feinberg MW, Sukhova GK, Colvin RA, Kihara S, Funahashi T, Luster AD, Libby P. Adiponectin inhibits the production of CXCR3 chemokine ligands in macrophages and reduces T lymphocyte recruitment in atherogenesis. Circ Res 2008;102:218-225. Rocha VZ, Folco EJ, Sukhova G, Shimizu K, Gotsman I, Vernon AH, Libby P. Interferon-gamma, a Th1 cytokine, regulates fat inflammation — a role for adaptive immunity in obesity. Circ Res 2008;103:467-476. Medoff BD, Okamoto Y, Leyton P, Sandall B, Raher M, Kihara S, Bloch KD, Libby P, Luster AD. Adiponectin-deficiency increases allergic airway inflammation and pulmonary vascular remodeling. Am J Respir Cell Molec Biol 2009; in press. Recent Reviews or Chapters: Libby P, Nathan DM, Abraham K, Brunzell JD, Fradkin J, Haffner SM, Hsueh W, Rewers M, Roberts T, Savage P, Skarlatos S, Wassef M, Rabadan-Diehl C. Report of the National Heart, Lung, and Blood Institute-National Institute of Diabetes and Digestive and Kidney Diseases Working Group on Cardiovascular Complications of Type 1 Diabetes Mellitus. Circulation 2005;111:3489-3493. Libby P, Plutzky J. Inflammation in diabetes mellitus: role of peroxisome proliferator-activated receptor–a and peroxisome proliferator-activated receptor–g agonists. Am J Cardiol 2007;99[suppl]:27B-40B. Beckman JA, Libby P, Creager MA. Diabetes mellitus, the metabolic syndrome, and atherosclerotic vascular disease. In: Libby P, Bonow RO, Mann DL, Zipes DP, Braunwald E, editors. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 8th edition. Philadelphia: Elsevier Saunders;2007. p. 1093-1106. Rocha VZ and Libby P. The multiple facets of the fat tissue. Thyroid 2008;18:175-183.