Author + information
- Xiaohan Jiang1,2,3,
- Qingqing Wu1,2,3,
- Yang Xiao1,2,3,
- Yuan Yuan1,2,3,
- Zheng Yang1,2,3,
- Zhouyan Bian1,2,3 and
- Qizhu Tang1,2,3
Evodiamine is one of the major components of Evodia rutaecarpa and has been demonstrated to restrain atherosclerosis and protect the myocardium against injury induced by ischemia-reperfusion. However, whether evodiamine could protect cardiac fibrosis and attenuate endothelial to mesenchymal transition (EndMT) remians unclear. This study was aimed to uncover the possible mechanism involved in the protecting effect of evodiamine from cardiac fibrosis and EndMT.
The C57BL/6 mice were randomly divided into 4 groups: control; cardiac fibrosis; low- and high-dose evodiamine (50 mg/kg, 100 mg/kg). Isoproterenol(ISO) was used to induce cardiac fibrosis and evodiamine was gavaged daily at the same time for 14 days. Then the cardiac function was evaluated by echocardiography. The degree of cardiac fibrosis and hypertrophy was assessed by pathological and molecular analyses of heart samples. Microvascular density (MVD) was evaluated by immuno histochemistry. The expression levels of CD31, CD34, α smooth muscle actin (α-SMA) and vimentin were detected by immuno-fluorescence staining and western blot analyses to evaluate the extent of EndMT.
After 14 days of ISO injection, the heart weight/body weight ratio(HW/BW) and heart weight/tibia length ratio(HW/TL) revealed no significant difference between ISO group and evodiamine treated group. Echocardiography revealed reduced interventricular septal thickness and left ventricular posterior wall thickness at end diastole in evodiamine treated group. Evodiamine also decreased cardiac fibrosis as accessed by normalization in collagen deposition and gene expression of hypertrophic and fibrotic markers. Evodiamine also prevented EndMT by increasing the expressions of CD31and CD34 while decreasing the expressions of α-SMA and vemintin, which in turn increased the MVD in heart. Furthermore, ISO-induced activation of TGF-β/Smad signal was blunted by evodiamine.
Evodiamine may attenuate cardiac fibrosis and EndMT which is probably mediated by the blockade of TGF-β/Smad pathway.