Table 1.

Examples of the Recent Experimental Studies for Cardiovascular Gene Therapy

	Therapeutic gene	Carrier/ Mode of regulation	Delivery	Application	Species	Therapeutic effect	References
Pre-emptive/ regulatable gene therapy	HO-1	Plasmid/ cardiac specific and hypoxia-regulated AAV/ constitutive (CMV) or hypoxia- regulated	Intramyocardial injection Intramyocardial injection	Myocardial infarction (I/R injury) Myocardial infarction (I/R injury)	mouse rat	attenuation of the formation of fibrotic scar amelioration of cardiac function – prevention of myocardial wall thining, inflammation and fibrosis	Tang et al., 2004​ ​​Pachori et al., 2004; ​2006
	VEGF	AAV/ Cardiac-specific and hypoxia-regulated	Intramyocardial injection	Ischemic heart	mouse	higher VEGF expression in ischemic heart, increased neovasculogenesis, less myocardial fibrosis, better cardiac fuction	Su et al., 2004
	SOD-3 (EC- SOD)	AAV/ constitutive (CMV) promoter	Intramyocardial injection	Myocardial infarction (I/R injury)	rat	decrease in infarct size 24h after I/R injury, improved ventricular function, enhanced survival	Agrawal et al., 2004
Novel proangiogenic genes	VEGF-D	Ad/ constitutive (CMV) promoter	Intramuscular injection	Ischemic hindlimb	rabbit	increased mean capillary area and vascular permeability, promotion of VSMC proliferation (arteriogenesis)	Rissanen et al., 2003
	Kallikrein	Ad/ Constitutive (CMV) promoter	Intramuscular injection	Ischemic and non-ischemic hindlimb	mouse	increased capillary density, enhanced perfusion	Emanueli et al., 2000;​ ​​2001
	Multigene approach: VEGF and Ang-1 Human CD34+ progenitor cells and VEGF-C	AAV/ constitutive (CMV) promoter plasmid/constitutive (CMV) promoter	Intramuscular injection Intramyocardial injection	Non-ischemic tibialis anterior muscle Ischemic heart	rat immunodeficient rat	Increased number of mature blood vessels Increased capillary density, reduced infarct size	Arsic et al., 2003​ ​​Shintani et al., 2006
Activation of endogenous genes	HIF-1α	Plasmid (HIF-1α/VP16 hybrid gene) AAV (HIF-1α without transactivation domain VP16)	Intramyocardial injection Intramuscular injection	Ischemic heart (acute myocardial infarction) Non-ischemic hindlimb	rat mouse	Enhanced angiogenesis, reduced infarct size increased capillary sprouting and proliferation, no increase in vascular leakage in the transduced muscle, enhanced perfusion	Shyu et al., 2002​ ​​Pajusola et al., 2005
	PR39	Ad/ constitutive (CMV) promoter	Intramyocardial catheterization	Chronically ischemic hart	pig	increased vessel size and number, improved myocardial perfusion and function	Post et al., 2006
Modification of progenitor cells: PB-EPC: autologous human MSCs:	eNOS or HO-1	Retroviral vector/ 5'LTR promoter	Catheter mediated instillation of EPCs	Balloon injury of the right common carotid artery	rabbit	enhanced reendotheliazation independently of EPC modification, reduced neointima size after delivery of eNOS-modified EPC	​​Kong et al., 2004
	GSK3β (inactive form)	Ad/constitutive	Direct cell injection into systemic arterial circulation	Ischemic hindlimb	immunodeficient mouse	Improved blood flow, limb salvage and tissue capillary density	Choi et al., 2004
	HO-1	Plasmid/ hypoxia-regulated promoter	Intramyocardial injection	Ischemic heart (acute myocardial infarction)	mouse	Improved viability of mesenchymal stem cells	Tang et al., 2005