Figure 4

Pro-apoptotic effect of statins, as assessed by DNA fragmentation. (A) Serum deprivation (SF) increased DNA fragmentation, compared to PASMCs cultured in presence of serum (5% FBS). Lipophilic statins such as simvastatin, fluvastatin and atorvastatin, but not the lipophobic pravastatin, promoted apoptosis in serum deprived cells. (B-C) Pro-apoptotic effect of simvastatin, fluvastatin and NO-releasing derivatives of pravastatin (6550) and fluvastatin (6553) reversed by mevalonate (MVA, 100 μM), but not by squalene (Squal, 100 μM). (D) Pro-apoptotic effect of exoenzyme C3 (C3) and Rho-kinase inhibitor Y-27632. Data are mean ± SEM of replicate values (n = 4) and representative of independent experiments with IPAH (A-B) and non-IPAH (C-D) cells. SF = serum free untreated cells.