Statins modulate expression of components of the plasminogen activator/plasmin system in human cardiac myocytes in vitro

Genes expressed in coronary thrombi are associated with ischemic time in patients with acute myocardial infarction

“…Unfortunately, we were not able to dissect the cell type responsible for the expressed genetic mediators. We can furthermore not exclude that the genes expressed are influenced by use of different medications prior to hospital admission, as well as by the acute pharmacological management of AMI, described for instance for statins [27].…”

Cardioprotective cytokine interleukin‐33 is up‐regulated by statins in human cardiac tissue

“…HACM and HACF were incubated in M199 containing 0.1% bovine serum albumin (BSA; Sigma) for 24 h prior to treatment with the respective substance. Thereafter, the medium was replaced with fresh M199 containing 0.1% BSA, and the cells were treated with different statins (atorvastatin, fluvastatin, lovastatin, simvastatin, or pravastatin) at concentrations from 0.5 to 5 μmol L −1 or BPs alendronate or ibandronate at concentrations from 1 nmol L −1 to 1 μmol L −1 for time periods up to 72 h. In additional experiments HACM and HACF were treated with fluvastatin, ibandronate, or alendronate in the absence or presence of MVA (100 μmol L −1 ), GGPP (10 μmol L −1 ), FPP (10 nm–1 μmol L −1 ), squalene (10 nm–1 μmol L −1 ), coenzyme Q10 (10 nm–1 μmol L −1 ), or U‐46619 (10 nmol L −1 ) for 48 h. Moreover, human cardiac cells were treated with Y‐27632 at 5 μmol L −1 or latrunculin B from 10 nmol L −1 to 1 μmol L −1 for 48 h. The concentrations of the substances used in this study were in the same range as concentrations used in numerous other tissue culture studies, including ours …”

“…Statins are considered to positively affect cardiac remodelling by attenuation of myocardial hypertrophy . Previous investigations from our group revealed modulating effects of statins on the plasminogen activator/plasmin system, apoptosis, and inflammation‐triggered B‐type natriuretic peptide in human cardiac cells. These mechanisms are implicated in the organisation of cardiac tissue and, as a consequence, in myocardial hypertrophy.…”

Inflammation and the cardiovascular system

“…HMG-CoA reductase inhibitors by decreasing PAI-1 and increasing t-PA expression in cardiac myocytes might be involved in the highly regulated spatio-temporal expression of components of the PA/plasmin system in the heart [53]. If these effects were also operative in vivo, one could speculate that statins via these mechanisms might participate in the modulation of tissue remodeling and repair in the human heart.…”

“…The PA/plasmin system and the MMP/TIMP system play an important role not only in the modulation of blood viscosity and vessel wall composition, as discussed above, but are also involved in ECM remodeling in the heart. Components of these systems PAI-1, t-PA, MMP-1, MMP-3, TIMP-1, and TIMP-2 are expressed in and secreted by human adult cardiac myocytes and/or cardiac fibroblasts [51][52][53]. CAD and especially MI are associated with activation of inflammatory cascades involving increased tissue and circulating cytokines such as IL-1, IL-6, and tumor necrosis factor-alpha (TNF-a) [54].…”