The Effects of Known Cardioprotective Drugs on Proinflammatory Cytokine Secretion From Human Coronary Artery Endothelial Cells

Background: Endothelial cell dysfunction in diabetes is involved in the pathogenesis and progression of premature atherosclerosis. High-dextrose has been shown to induce both oxidative stress and endoplasmic reticulum stress in cultured human coronary artery endothelial cells (HCAEC). Study Question: To determine whether or not several classes of cardioprotective drugs inhibit proinflammatory cytokine expression by HCAEC. Measures and Outcomes: To determine the effects of high dextrose on expression of proinflammatory cytokines by HCAEC, cells were treated with either 5.5 mM or 27.5 mM dextrose for 24 hours and interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor a were measured by enzyme immunoassay in the presence or absence of known cardioprotective drugs, including select b-blockers, statins, and renin-angiotensin system inhibitors. Results: IL-1 beta levels increased significantly in cells treated with high dextrose; however, IL-6 and IL8 levels did not change. Treatment of cells with carvedilol, atenolol, and propranolol decreased levels of all 3 cytokines in cells exposed to either 5.5 or 27.5 mM dextrose. Similar effects on IL-1 beta, IL-6, and IL-8 levels were observed when cells were treated with simvastatin, pravastatin, and the reninangiotensin system inhibitors spironolactone, captopril, lisinopril, candesartan, and losartan. No Il-2 or tumor necrosis factor a expression was observed in any of the experiments indicating that HCAEC do not express these cytokines. Conclusions: We conclude that each of the classes of drugs tested possess pleiotropic antiinflammatory activities and are effective in both low-and high-dextrose-treated cells.