Mechanism of Profilin—1 in regulating eNOS/NO signaling pathway and its role in hypertensive myocardial hypertension

OBJECTIVE: To explore the mechanism of Profilin-1 in regulating eNOS/NO pathway and its role in the development of myocardial hypertrophy. METHODS: Spontaneously hypertensive rats (SHR) aged 5 weeks were injected with different adenovirus vectors to induce Profilin-1 expression knockdown (SHR-I) or over express (SHR-H) or to use as control (SHR-C). All these treatment were compared with Wistar-Kyoto rats (SKY) treated with control adenovirus vectors (WKY-C). The same injection was executed at the sixth week during the experiment of 12 weeks. After experiment, the left ventricular weight-to-heart weight ratio (LVW/HW) and left ventricular long axis (LVLA) were measured. Meanwhile, NO contents in blood and myocardium, Profilin-1, eNOS and Caveolin-3 mRNA and protein levels and phosphorylated eNOS (P-eNOS) protein level in myocardium were determined. RESULTS: Compared with WKY-C group, the SHR-C group was statistically higher in LVW/HW (0.79±0.03), LVLA (11.82±0.58 mm) and Profilin-1 mRNA and protein level (P<0.05), but lower in NO content [(18.63±6.23) μmol/L] in blood and [(2.71±0.17) μmol/L] in myocardium), eNOS activity and Caveolin-3 expression (P<0.05). The over expressing Profilin-1 led SHR-H group to a higher value of LVW/HW [(0.93±0.03) mm and LVLA (14.17±0.69) mm] in comparison with SHR-C group (P<0.05), and to a lower value of NO content (in myocardium), eNOS activity and Caveolin-3 expression (P<0.05); however, this phenomenon was reversed by the knockdown Profilin-1 expression (SHR-I group). CONCLUSIONS: Profilin-1 expression, being negative in regulating Caveolin-3 expression and eNOS/NO pathway activity, promotes the development of myocardial hypertrophy which can be reversed by Profilin-1 silencing.