Table 1.

Therapeutic potential of circRNAs in CVD.

Name (Species)	Investigated disease	Expression in disease	Endogenous function	Target cells (indirect evidence)	Protection from disease through	Mouse models in vivo	Dose; route	Reference
MFACR	Myocardial infarction	Up	Deleterious	Cardiomyocytes?	circRNA KD	Injection of adenovirus expressing shRNAs against MFACR into the aortic root rescues from heart dysfunction (I/R-induced heart injury mouse model).	2 × 1011 Pfu; once per 14 days	Wang et al., 2016, 2017
HRCR	Heart failure (cardiac hypertrophy)	Down	Protective	Cardiomyocytes?	circRNA OE	Injection of HRCR-generating adenovirus into jugular vein rescues from cardiac hypertrophy (ISO-induced heart injury mouse model).	2 × 1011 Pfu; once per 14 days	Wang et al., 2016
circAmotl1	Heart failure (Cardiomyopathy)	n.d.	Protective	Cardiomyocytes?	circRNA OE	Intraperitoneally injection of nanoparticles with mPEG-SH-formulated DNA plasmid (pBS) expressing human circAmotl1 ameliorates ventricle dilation and stress-induced cell death (dox-induced mouse cardiomyopathy model).	100 mg plasmid; 2-3x per week	Zeng et al., 2017
circFoxo3	Heart failure (senescence, cardiomyopathy)	Up	Deleterious	Cardiomyocytes, fibroblasts?	circRNA KD	Injection of PEG-(10-nm) gold nanoparticle with siRNAs against circFoxo3 ameliorates doxorubicin-induced cardiomyopathy.	6 μg, 3 times/week	Du et al., 2017b
circHipk3	Diabetic retinopathy	Up	Deleterious	Retinal vascular endothelial cells?	circRNA KD	Intravitreal injection of adenovirus-encoded shRNAs targeting circHIPK3 in a mouse model for diabetic retinopathy is protective.	1.5 × 109 Pfu; once per month	Shan et al., 2017
cZnf609	Ischemic retinopathy	Up	Deleterious	Retinal vascular endothelial cells?	circRNA KD	Intravitreal injection of adenovirus-encoded shRNAs against cZNF609 ameliorates retinopathy in diabetic and hyperoxia-induced mouse retinopathy models.	1 × 107 Pfu; once-twice per week	Liu et al., 2017
circDlgap4	Stroke	Down	Protective	Brain endothelial cells?	circRNA OE	Injection of circDLGAP4-generating lentivirus ameliorates brain damage in a transient middle cerebral artery occlusion mouse model.	5 × 108 Pfu; once per 2 weeks	Bai et al., 2018

List of studies where levels of circRNAs have been manipulated with a therapeutic success in animal CVD models in vivo. CVD, cardiovascular disease; I/R, ischemia/reperfusion; ISO, isoproterenol; KD, knockdown; mPEG-SH, thiol-functionalized methoxyl polyethylene glycol; OE, overexpression; Pfu, plaque forming unit; shRNA, short hairpin interfering RNA.