ZYZ-168 alleviates cardiac fibrosis after myocardial infarction through inhibition of ERK1/2-dependent ROCK1 activation

Selective treatments for myocardial infarction (MI) induced cardiac fibrosis are lacking. In this study, we focus on the therapeutic potential of a synthetic cardio-protective agent named ZYZ-168 towards MI-induced cardiac fibrosis and try to reveal the underlying mechanism. ZYZ-168 was administered to rats with coronary artery ligation over a period of six weeks. Ecocardiography and Masson staining showed that ZYZ-168 substantially improved cardiac function and reduced interstitial fibrosis. The expression of α–smooth muscle actin (α-SMA) and Collagen I were reduced as was the activity of matrix metalloproteinase 9 (MMP-9). These were related with decreased phosphorylation of ERK1/2 and expression of Rho-associated coiled-coil containing protein kinase 1 (ROCK1). In cardiac fibroblasts stimulated with TGF-β1, phenotypic switches of cardiac fibroblasts to myofibroblasts were observed. Inhibition of ERK1/2 phosphorylation or knockdown of ROCK1 expectedly reduced TGF-β1 induced fibrotic responses. ZYZ-168 appeared to inhibit the fibrotic responses in a concentration dependent manner, in part via a decrease in ROCK 1 expression through inhibition of the phosphorylation status of ERK1/2. For inhibition of ERK1/2 phosphorylation with a specific inhibitor reduced the activation of ROCK1. Considering its anti-apoptosis activity in MI, ZYZ-168 may be a potential drug candidate for treatment of MI-induced cardiac fibrosis

Sur la présence de rhyncholites dans le Lias et le Dogger des Préalpes médianes romandes (Suisse)

Neuf espèces de rhyncholites des genres Akidocheilus, Leptocheilus et Hadrocheilus du Lias supérieur et du Dogger sont décrites dans les Préalpes médianes romandes (Suisse). Le genre Eurycheilus n. gen., espèce type E. fallbachensis n. sp., est introduit. L'intérêt stratigraphique des rhyncholites est discuté et un essai de zonation du Lias supérieur et du Dogger au moyen de ces microfossiles est proposé. Les rhyncholites sont admis comme rattachés à un groupe de céphalopodes inconnus et éteints, exceptés ceux se rapportant aux nautiles. Des éléments nouveaux concernant la microstructure des rhyncholites sont présentés