Chlamydia pneumoniae Heat Shock Protein 60 Enhances Expression of ERK, TLR-4 and IL-8 in Atheromatous Plaques of Coronary Artery Disease Patients

Abstract

Chlamydia pneumoniae heat shock protein (cHSP) 60 is produced during chronic chlamydial infection and activate innate immune and inflammatory responses thereby contributing to atherogenesis. However, to date there is no apparent signaling cascade delineated in human atherosclerotic plaques in C. pneumoniae positive coronary artery disease (CAD) patients. Atherosclerotic plaques were obtained from 40 CAD patients (28 men, 12 women) attending Department of Cardio Thoracic and Vascular Surgery Safdarjung Hospital, New Delhi. Atherosclerotic plaques were used for gene expression studies at RNA level by real-time PCR and to study expression of ERK1/2, JNK1/2, NF-kB, IkkB and MCP-1 at protein level by immunoblotting. Significantly higher (p < 0.001) RNA expression was found for IL-8, TLR-2/4, TGF-β, ICAM1, VCAM1 and MAPKinase genes, whereas significantly lower (p < 0.001) RNA expression for SMAD4, IkkB, BRCA1 and IL-10 was detected in cHSP60-positive atheromatous plaque of CAD patients. Moreover, at proteins level pERK1/2 (p = 0.05), NF-kB (p = 0.017), MCP-1 (p = 0.011) was higher and IkkB expression was lower (p = 0.038) in cHSP60-positive atheromatous plaque of CAD patients. This study by using human atheromatous plaques at RNA and protein levels demonstrated higher expression of TLR-2/4, IL-8, ICAM1, VCAM1, ERK1/2 and NF-kB in cHSP60-positive CAD patients.

• MAPKinase
• Signal Transduction
• Immunoblotting
• Real-Time PCR array
• Infection

ACKNOWLEDGMENTS

The study was funded by Department of Science and Technology, SR/SO/HS-6/2005, India. Indian council of Medical research is acknowledged for providing financial assistance to Hem Chandra Jha and Pragya Srivastava in the form of fellowships. We thank Dr. Sumit and all operation theater staff of the Department of Cardio Thoracic and Vascular Surgery, Safdarjung Hospital, for the atherosclerotic specimens. We also thank Dr. L. C. Singh for consistently support in running real-time PCR experiments.