Limits...
VEGF attenuates development from cardiac hypertrophy to heart failure after aortic stenosis through mitochondrial mediated apoptosis and cardiomyocyte proliferation.

Xu XH, Xu J, Xue L, Cao HL, Liu X, Chen YJ - J Cardiothorac Surg (2011)

Bottom Line: AS for four weeks caused cardiac hypertrophy and left ventricular dysfunction.VEGF treatment increased capillary density, protected mitochondrial function, reduced CMs apoptosis, promoted CMs proliferation and eventually preserved cardiac function.Our findings indicate that VEGF could repair AS-induced transition from compensatory cardiac hypertrophy to heart failure.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P R China.

ABSTRACT

Background: Aortic stenosis (AS) affects 3 percent of persons older than 65 years and leads to greater morbidity and mortality than other cardiac valve diseases. Surgery with aortic valve replacement (AVR) for severe symptomatic AS is currently the only treatment option. Unfortunately, in patients with poor ventricular function, the mortality and long-term outcome is unsatisfied, and only a minority of these patients could bear surgery. Our previous studies demonstrated that vascular endothelial growth factor (VEGF) protects cardiac function in myocardial infarction model through classic VEGF-PI3k-Akt and unclear mitochondrial anti-apoptosis pathways; promoting cardiomyocyte (CM) proliferation as well. The present study was designed to test whether pre-operative treatment with VEGF improves AS-induced cardiac dysfunction, to be better suitable for AVR, and its potential mechanism.

Methods: Adult male mice were subjected to AS or sham operation. Two weeks later, adenoviral VEGF (Ad-VEGF), enhanced green fluorescence protein (Ad-EGFP, as a parallel control) or saline was injected into left ventricle free wall. Two weeks after delivery, all mice were measured by echocardiography and harvested for further detection.

Results: AS for four weeks caused cardiac hypertrophy and left ventricular dysfunction. VEGF treatment increased capillary density, protected mitochondrial function, reduced CMs apoptosis, promoted CMs proliferation and eventually preserved cardiac function.

Conclusions: Our findings indicate that VEGF could repair AS-induced transition from compensatory cardiac hypertrophy to heart failure.

Show MeSH

Related in: MedlinePlus

Ad-VEGF increases expression of VEGF (A), p-Akt (B) protein two weeks after viral injection. *P < 0.05, TAC vs. Sham; †P < 0.05, VEGF vs. TAC.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3094376&req=5

Figure 5: Ad-VEGF increases expression of VEGF (A), p-Akt (B) protein two weeks after viral injection. *P < 0.05, TAC vs. Sham; †P < 0.05, VEGF vs. TAC.

Mentions: After 2 weeks injection of adenovirus containing VEGF in hypertrophied hearts, western blot analysis showed that levels of VEGF were increased in VEGF group compared with that in other groups (Fig 5A, P < 0.05). To investigate whether VEGF could activate PI3K-Akt signaling in the myocardium, we examined the level of phospho-Akt and Akt in the myocardium. As shown in Figure 5B, significant increase in the ratio of phosphor-Akt/Akt was observed in the VEGF group compared with that in other groups (P < 0.05). Thus, Ad-VEGF injection increased expression of VEGF and phospho-Akt in myocardium.


VEGF attenuates development from cardiac hypertrophy to heart failure after aortic stenosis through mitochondrial mediated apoptosis and cardiomyocyte proliferation.

Xu XH, Xu J, Xue L, Cao HL, Liu X, Chen YJ - J Cardiothorac Surg (2011)

Ad-VEGF increases expression of VEGF (A), p-Akt (B) protein two weeks after viral injection. *P < 0.05, TAC vs. Sham; †P < 0.05, VEGF vs. TAC.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3094376&req=5

Figure 5: Ad-VEGF increases expression of VEGF (A), p-Akt (B) protein two weeks after viral injection. *P < 0.05, TAC vs. Sham; †P < 0.05, VEGF vs. TAC.
Mentions: After 2 weeks injection of adenovirus containing VEGF in hypertrophied hearts, western blot analysis showed that levels of VEGF were increased in VEGF group compared with that in other groups (Fig 5A, P < 0.05). To investigate whether VEGF could activate PI3K-Akt signaling in the myocardium, we examined the level of phospho-Akt and Akt in the myocardium. As shown in Figure 5B, significant increase in the ratio of phosphor-Akt/Akt was observed in the VEGF group compared with that in other groups (P < 0.05). Thus, Ad-VEGF injection increased expression of VEGF and phospho-Akt in myocardium.

Bottom Line: AS for four weeks caused cardiac hypertrophy and left ventricular dysfunction.VEGF treatment increased capillary density, protected mitochondrial function, reduced CMs apoptosis, promoted CMs proliferation and eventually preserved cardiac function.Our findings indicate that VEGF could repair AS-induced transition from compensatory cardiac hypertrophy to heart failure.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P R China.

ABSTRACT

Background: Aortic stenosis (AS) affects 3 percent of persons older than 65 years and leads to greater morbidity and mortality than other cardiac valve diseases. Surgery with aortic valve replacement (AVR) for severe symptomatic AS is currently the only treatment option. Unfortunately, in patients with poor ventricular function, the mortality and long-term outcome is unsatisfied, and only a minority of these patients could bear surgery. Our previous studies demonstrated that vascular endothelial growth factor (VEGF) protects cardiac function in myocardial infarction model through classic VEGF-PI3k-Akt and unclear mitochondrial anti-apoptosis pathways; promoting cardiomyocyte (CM) proliferation as well. The present study was designed to test whether pre-operative treatment with VEGF improves AS-induced cardiac dysfunction, to be better suitable for AVR, and its potential mechanism.

Methods: Adult male mice were subjected to AS or sham operation. Two weeks later, adenoviral VEGF (Ad-VEGF), enhanced green fluorescence protein (Ad-EGFP, as a parallel control) or saline was injected into left ventricle free wall. Two weeks after delivery, all mice were measured by echocardiography and harvested for further detection.

Results: AS for four weeks caused cardiac hypertrophy and left ventricular dysfunction. VEGF treatment increased capillary density, protected mitochondrial function, reduced CMs apoptosis, promoted CMs proliferation and eventually preserved cardiac function.

Conclusions: Our findings indicate that VEGF could repair AS-induced transition from compensatory cardiac hypertrophy to heart failure.

Show MeSH
Related in: MedlinePlus