Effects of aliskiren on homocysteine-induced matrix expression in cultured cardiac fibroblasts.

<p>Fibroblasts were cultured in the presence or absence of D,L, homocysteine 200 µmol/L for 24 hours after pretreatment with varying concentrations of aliskiren (0.1–10 µmol/L). Real time PCR was done to measure relative expression of COLIA2 (alpha 2 chain of type I collagen; A) and COL3A1 (alpha 1 chain of type III collagen; B) genes. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081612#pone-0081612-g005" target="_blank">Figure 5C</a> demonstrates the results of real time PCR to compare the effects of losartan and captopril with aliskiren on homocysteine induced expression of COL1A2 gene. Western blotting was conducted to measure the expression of collagen type I protein (D and E) Glyceraldehyde 3 phosphate dehydrogenase (GAPDH) was used as internal control. Hcy-D,L, homocysteine; AL-aliskiren; Los – losartan; and Cap – captopril. *p<0.05.</p

Effects of aliskiren on Hhe-induced diastolic dysfunction.

<p>(n = 5–7/group). A, the relation of balloon volume (normalized to heart weight) to left ventricular developed pressure. There were no differences between the groups. B shows the relation of balloon volume to left ventricular end diastolic pressure. There was a significant displacement of the pressure volume curve upwards in the Hhe group compared to all other groups (ANOVA; p<0.05). Hhe – Hhe-inducing diet; LVEDV – left ventricular end diastolic volume; and LVDevP – left ventricular developed pressure.</p

Role of Akt pathway in aliskiren's effects on attenuating collagen expression.

<p>A and B demonstrate the results of Western blotting for phospho- and total Akt in hearts of mice treated with various diets. C shows changes in the protein levels of collagen type I, phospho- and total Akt in response to 24 hours of exposure to D,L. Homocysteine (200 µmol/L) with or without pre-treatment with aliskiren 10 µmol/L (AL), wortmannin 1 µmol/L or Akt Inhibitor VIII 1 µmol/L. Hhe – Hhe-inducing diet; D,L, homocysteine (lower panel); AL 0.05– aliskiren 0.5 mg/kg/day; AL 5– aliskiren 5 mg/kg/day; AL 50– aliskiren 50 mg/kg/day; Wort – wortmannin; Akt in – Akt inhibitor VIII. *p<0.05; **p<0.01; and ***p<0.001.</p