Upregulation of TH/IL-17 Pathway-Related Genes in Human Coronary Endothelial Cells Stimulated with Serum of Patients with Acute Coronary Syndromes.

BACKGROUND: Inflammation plays an essential role in the development and complications of atherosclerosis plaques, including acute coronary syndromes (ACS). Indeed, previous reports have shown that within the coronary circulation of ACS patients, several soluble mediators are released. Moreover, it has been demonstrated that endothelial dysfunction might play an important role in atherosclerosis as well as ACS pathophysiology. However, the mechanisms by which these soluble mediators might affect endothelial functions are still largely unknown. We have evaluated whether soluble mediators contained in serum from coronary circulation of ACS patients might promote changes of gene profile in human coronary endothelial cells (HCAECs).

METHODS: HCAECs were stimulated in vitro for 12 h with serum obtained from the coronary sinus (CS) and the aorta (Ao) of ACS patients; stable angina (SA) patients served as controls. Gene expression profiles of stimulated cells were evaluated by microarray and real-time PCR.

RESULTS: HCAECs stimulated with serum from CS of ACS patients showed a significant change (upregulation and downregulation) in gene expression profile as compared with cells stimulated with serum from CS of SA patients. Moreover, ad hoc sub analysis indicated the upregulation of Th-17/IL-17 pathway-related genes.

CONCLUSION: This study demonstrates that, in ACS patients, the chemical mediators released in the coronary circulation might be able to perturb coronary endothelial cells (ECs) modifying their gene profile. These modified ECs, through downregulation of protective gene and, mainly, through upregulation of gene able to modulate the Th-17/IL-17 pathway, might play a key role in progression of coronary atherosclerosis and in developing future acute events.