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Figure 3 Involvement of caspases in apoptosis induction in CHF and apoptosis suppression by carvedilol. A, Effect of carvedilol (5 µmol/liter) and the caspase inhibitor ZVAD-fmk (100 µmol/liter) on HUVEC apoptosis induced by the serum of control subjects (n = 7) or patients with CHF (n = 10). *p < 0.001 vs. CHF serum in the absence of the compounds; **p < 0.001 vs. control group. B, Suppression of CHF serum-induced DNA fragmentation by carvedilol (5 µmol/liter). C, Effect of carvedilol (5 µmol/liter) on DNA laddering induced by TNF-alpha (50 ng/ml; 18 h). Upper panel, amounts of DNA loaded. A representative autoradiographic study, out of three experiments, is shown. D, Dose-dependent inhibition of TNF-alpha–induced apoptosis by carvedilol, its analogue BM91.0228 and propranolol. 100% HUVEC apoptosis induced by TNF-alpha (50 ng/ml; 18 h). *p < 0.001 vs. carvedilol or BM91.0228 at the respective concentration (n = 4 to 6).
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