ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Objective To observe the change of profilin-1 during the aging of rats' aorta and the anti-aging effect of grape procyanidins (GPC).Methods Young male Wistar rats (9 weeks) and middle rats (12 months) were randomly divided into GPC treatment and control groups respectively.We quantified arterial aging changes through morphological methods.Thoracic aortas were stained with hematoxylin eosin.Serum levels of 3-nitrotyrosine (3-NT),malondialdehyde (MDA),superoxide dismutase (SOD) and nitric oxide (NO) were tested using enzyme-linked immunosorbent assay (ELISA).Western blotting was performed to measure the protein expression of inducible nitric oxide synthase (iNOS) and profilin-1.Results Compared with the young male Wistar rats group,aging change in the aortic morphology of middle rat group were shown by hematoxylin-eosin staining (HE) staining:media thickness (MT) increased [(98.3±0.5)μm vs.(83.1±1.0)μm,P＜0.05],luminal internal diameter (LD) decreased [(15.5 ±0.2) μm vs.(18.2±0.5,P＜0.05)μm,P＜ 0.05],(MT/LD)％ increased [(6.4±0.1) ％ vs.(4.6±0.1)％,P＜0.05],the protein expressions of profilin-1 and iNOS both increased [profilin-1:(1.58 ± 0.09) vs.(1.29 ± 0.04),iNOS:(1.02±0.12) vs.(0.75±0.02),both P＜0.05],levels of NO and SOD in serum decreased [NO:(6.3±0.2)μmol/L vs.(8.4±0.2) μmol/L,SOD:(172.3±1.6) U/ml vs.(189.1±1.5) U/ml,both P＜0.05],the levels of MDA and 3-NT increased[MDA:(11.3±0.3) μmol/L vs.(9.4 ±0.1) μmol/L,3 NT:(40.2±0.3) nmol/L vs.(35.6±0.5) nmol/L,both P＜0.05)].After treatment with GPC,compared with the control group,MT decreased,LD increased and MT/LD (％)decreased in the middle GPC treatment group.The protein expressions of profilin-1 had no changes before and after treatment with GPC both in young and middle groups.After the GPC treatment in middle group,compared with the middle control group,iNOS expression decreased,serum levels of NO and SOD increased,and the levels of MDA and 3-NT decreased significantly (all P ＜0.05).Conclusions Profilin-1 is related with age-related changes in rat aorta.Profilin-1 participates in vascular aging through iNOS induced oxidative stress.GPC may defer vascular aging by inhibiting vascular oxidative stress.