Abstract 2275: Reverse Remodeling of Left Ventricular Hypertrophy Restores the Angiogenic Potential of The Myocardium
Objective: Cardiac hypertrophy is an adaptive response to increased workload. If unrelieved, lack of adaptive tissue capillary growth impairs myocardial perfusion and contributes to heart failure. Factors influencing myocardial angiogenesis include the balance of angiogenesis stimulators and inhibitors. We hypothesized that angiogenesis inhibitors are elevated in hypertrophying myocardium without adaptive increase of angiogenesis stimulators and that relief of the pressure load reestablishes this balance.
Method: LV hypertrophy model (banded animals): 10-day-old rabbits underwent banding of the descending aorta. Relief of pressure load (debanded animals): surgical removal of the band was performed at 4 – 6wks of age (compensated hypertrophy). Banded and debanded animals were followed by serial echocardiography measuring contractile function (%SF=shortening fraction). At 12wks all animals (n=6/group) were euthanized and angiogenesis inhibitors (endostatin, angiostatin) and stimulators (vascular endothelial growth factor; VEGF) were determined by immunoblotting (arbitrary densitometry units). Data are expressed as mean±SEM with P<0.05 considered significant by t-test.
Results: %SF significantly declined in banded animals over the 12 weeks, but returned to baseline with band removal (banded: 31±1 versus debanded: 41±3; p<0.05). Angiogenesis inhibitors were significantly elevated in banded compared to debanded animals: angiostatin (banded: 168±4 versus debanded: 157±2; p<0.05) and endostatin (banded: 175±1 versus debanded: 170±1; p<0.05). VEGF levels had increased in the myocardium after band removal (debanded: 156±1 versus banded: 149±3; p<0.05) by the 12wks time point.
Conclusion: Lack of angiogenic response of the hypertrophying myocardium in response to pressure-overload likely results from enhanced production of angiogenesis inhibitors (angiostatin and endostatin). Removal of the aortic constriction reestablishes the balance between angiogenesis inhibitors and stimulators preserving the pro-angiogenic potential of the hypertrophied myocardium.