Aims: 

The pathogeny of primary dilative forms of cardiomyopathy remains unclear. Vascular endothelial growth factor (VEGF) regulates angiogenesis and vascular tone. Disruption of coordinated hypertrophy and angiogenesis contributes to the transition to heart failure (HF) while dysregulation of vascular tone and remodeling contributes to pulmonary hypertension secondary to left HF. Moreover, in the embryo, VEGF controls ventricular contractility independently of perfusion. We examined pulmonary and cardiac gene expressions of VEGF, VEGF-R1 and VEGF-R2 in a canine model of tachycardiomyopathy and related these results to functional alterations.

Methods: 

Eight beagle dogs with overpacing-induced HF underwent over a 7 week period weekly haemodynamic measurements, echocardiograms and endomyocardial biopsies, post-mortem pulmonary arterial reactivity, and RTQ-PCR for mRNA quantification. Six healthy dogs served as controls.

Results: 

Cardiac VEGF and VEGF-R1 progressively decreased from week 1 of pacing vs. week 0); these changes were correlated with left ventricular ejection fraction and volumes. Mean pulmonary arterial pressure increased from week 4. In vitro pulmonary arteries showed decreased relaxation to acetylcholine and increased hypercontraction in phenylephrine precontracted rings after antagonism of NO or prostaglandins. VEGF and VEGF-R2 were overexpressed in lung arteries vs. control.

Conclusion: 

Tachycardia-induced HF is characterized by early downregulation of cardiac VEGF-VEGF-R1 and upregulation of pulmonary VEGF-VEGF-R2. Disruption of this system may represent a mechanism in the progression of non-ischaemic dilated cardiomyopathy.