Table 3.

Preclinical gene therapy studies for heart failure and other cardiovascular diseases

Molecular target	Model	Vector	Findings	Refs
VEGF-A165	Coronary artery occlusion model in adult sheep	Plasmid DNA CMVenh/p-VEGF-A165 (3.8 mg)	– Reduction of 30% in infarct size – Improvement in myocardial perfusion and LV wall motion	92
	Occlusion of the LAD coronary artery in dogs	Adeno-associated virus AAV6-CMVp- VEGF-A165 (5 × 1012 vp)	– LV and arterial pressure, and ejection fraction were not significantly different between the groups – Improvement in tissue viability and cardiac function	93
	Occlusion of the LAD coronary artery in pigs	Adeno-associated virus AAV1-MLCp- VEGF-A165 (1 × 1012 vp)	– Co-expression VEGF and Ang1 induced angiogenesis, stimulated cardiomyocyte proliferation, and reduced apoptosis	94
FGF4	Pig model of chronic myocardial ischaemia	Adenovirus Ad5-CMVp-PR39 (3 × 109 vp)	– Increase in myocardial blood flow at the peak of dobutamine-induced stress – Improved regional ventricular function	95
	Stress-induced myocardial ischaemia in pigs	Adenovirus Ad5-CMVp-FGF4 (up to 1.6 × 1012 vp)	– Improve regional and myocardial function and perfusion after 12 weeks post-injection	34
Sarcoplasmic reticulum Ca2+-ATPase	Human ventricular myocytes from patients with end-stage heart failure	Adenovirus Ad5-CMVp-SERCA2a	– Increased pump activity and contraction velocity – Improved Ca2+ concentration in systole and diastole	96
	Ascending aortic constriction in rats	Adenovirus Ad5-CMVp-SERCA2a	– Improved left ventricular systolic pressure and contractility parameters	97
	Heart failure post-MI model in sheep	Adeno-associated virus AAV6-CMVp-SERCA2a (5 × 1012 vp)	– Improved left ventricular remodelling – Decreased caspase 3 levels (anti-apoptotic effect)	98
	Rats with ligation of the left anterior descending artery	Adenovirus Ad-CMVp-SERCA2a (2 × 1011 vp)	– Improvements in regional-wall motion and anterior-wall thickening – Reduction of ventricular arrhythmias during Ischaemia/Reperfusion	99
	Pressure-overload model of heart failure in guinea pigs	Adeno-associated virus AAV1-CMVp-SERCA2a	– Increased left ventricle fractional shortening – Reduced susceptibility to inducible ventricular arrhythmias	100
S100A1	Rat model of heart failure	Adeno-associated virus AAV6-actin-S100A1 (2.5 × 1011 vp)	– Improved contractility – Improvement of left ventricular dysfunction and remodelling	101
	Heart failure due to balloon occlusion of the left circumflex coronary artery in domestic pigs	Adeno-associated virus AAV9-CMVenh/MLCp-S100A1 (1.5 × 1013 vp)	– Restoration of S100A levels with improved Ca2+ handling and energy homeostasis – Improved contractility	102
β-Adrenergic receptor	Catheterization of coronary artery in rabbits	Adenovirus Ad-CMVp-β2-AR (5 × 1011 vp)	– Improved left ventricular systolic function	103
	Rat model of hypertrophied heart failure	Plasmid DNA	– Improved contractility response to isoproterenol	104
	Rat model of post-MI heart failure	Adenovirus Ad-β2-AR	– Improved basal and isoproterenol-stimulated cardiac contractility	105
Adenylyl-cyclase 6	Wild-type C57/B6 mice	Adenovirus Ad.AC6 (2.5 × 1010 vp)	– Increased myocardial contractility – Improved LV function	106
	Transgenic mice overexpressing adenylyl cyclase (AC) type 6	n/a	– Increased LV ejection fraction – Improvements in both systolic and diastolic LV function	107
	Transgenic mice overexpressing adenylyl cyclase (AC) type 6	n/a	– Poor response to chronic pressure overload and increased deterioration in contractility parameters	108
	Porcine model of heart failure	Adenovirus Ad-CMVp-AC6 (1.4 × 1012 vp)	– Improved left ventricular remodelling parameters – Improved LV function (increased fractional shortening and velocity of circumferential fibre shortening) – Increased cAMP levels	109