Atrial natriuretic peptide antifibrotic properties are mainly described in cardiac myocytes or in induced cardiac myofibroblasts (Angiotensin II or TGF-β induced differentiation). In the present work, we investigate the effects of ANP/NPRA/cGMP system in modulating rat cardiac fibroblasts function. Cardiac fibroblasts were isolated from adult Wistar male rats and cultured in the presence of serum in order to induce fibroblasts differentiation. Cultures were then treated with ANP (1 μM), 8-Br-cGMP (100 μM) or IBMX (100 μM), a non-specific phosphodiesterases inhibitor. ANP significantly decreased proliferation rate and collagen secretion. Its effect was mimicked by t he c GMP a nalog, w hile c ombining A NP w ith 8 -Br-cGMP did not lead to additional effects. Moreover intracellular cGMP levels were elevated when cells were incubated with ANP confirming that ANP intracellular pathway is mediated by cGMP. Additionally, immunoblotting and immunofluorescence were used to confirm the presence of guanylyl cyclase specific natriuretic peptide receptors A and B. Finally we scanned specific cGMP dependent PDEs via RT-qPCR, and noticed that inhibiting all PDEs led to an important decrease in proliferation rate. Effect of ANP became more prominent after 10 culture days, confirming the importance of ANP in fibroblasts to myofibroblasts differentiation. Uncovering cellular aspects of ANP/NPRA/cGMP signaling system provided more elements to help understand cardiac fibrotic process., M. Moubarak, C. Magaud, Y. Saliba, A. Chatelier, P. Bois, J.-F. Faivre, N. Farès., and Obsahuje bibliografii
The objective of this study was to assess a possible link between microalbuminuria (MA), a major ri sk factor of the cardiorenal syndrome and the brain natriuretic peptide (BNP), a marker of cardiac hypertrophy. Two kidney-one clip (2K-1C) renovascular hypertension was induced in 24 male Wistar rats (weighing 220-250 g). Rats were randomized into four groups for 8 weeks: Sham, not treated; Bos, treated with bosentan; Cap, treated with captopril; Bos/Cap, treated with both drugs. Blood pressure, plasma BNP and transforming growth factor β1 (TGF-β1) concentrations, microalbuminuria and creatininemia as well as cardiac mass, BNP, α- and β-myosin heavy chain (MHC) gene expression and kidney histology were determined. Following stenosis, Sham rats developed hypertension (p<0.001), an increase in BNP (p<0.05) and TGF-β1 (p<0.005) concentrations, creatinine levels (p<0.001), and urinary albumin (p<0.001). Under drug treatment, decreases in blood pressure (p<0.001), creatinine levels (p<0.05), plasma TGF-β1 (p<0.005) and BNP (p<0.05) concentrations, were co ncomitant with the absence of MA which was significantly correlated with reductions in cardiac mass (p<0.05) and hypertrophy markers (BNP and β-MHC gene expression) (p<0.005) as well as in renal fibrosis. These findings suggest a potential link between microalbuminuria evolution and BNP as well as a possible effect of microalbuminuria-lowering therapy on halting the progression, or even inducing the regression of cardiac hypertrophy., Y. Saliba, E. Chouery, A. Mégarbané, H. Jabbour, N. Farès., and Obsahuje bibliografii