Table 3.

circRNAs and circRNA regulators in cardiovascular disease in vivo. List of circRNAs implicated as regulators of cardiovascular disease entities by in vivo evidence. Levels of expression and proposed functions in vivo are indicated. Asterisks (*) mark RNA-binding proteins that have been functionally studied and linked to CVD, and which have independently been found to regulate also circRNA biogenes - It is not known whether their role as circRNA regulators has any impact on their role in CVD.

Name (Species)	Disease	Regulation (in Disease)	Function	Mouse Models	Role in vivo	Ref.
HRCR (m.m.)	Heart injury	Down	Protective	Cardiomyocytes?	ISO-induced heart injury mouse model: vein-injected HRCR-expressing construct rescued from cardiac hypertrophy	[170]
MFACR (m.m.)	Heart injury	Up	Deleterious	Cardiomyocytes?	I/R-induced heart injury mouse model: intracoronary injection of MFCR siRNA rescued from heart dysfunction	[171]
Cdr1as (m.m.)	MI	Up	Deleterious	Heart	LAD ligation-induced MI in mouse: intracardially injected CDR1as-expressing construct prior to MI increased infarction size	[143]
MBNL* (h.s. m.m. d.r.)	DM	Down	Protective	Cardiac muscle	•Mouse double KO (Mbnl1−/−; Mbnl2+/−): DM-like phenotypes (atrial dilatation left ventricular hypertrophy, arrhythmias) •Zebrafish Mbnl2 mutant: DM-like heart defects •Expression correlation in human: CUG repeat-expressing RNA inhibits MBNL	[236] [237] [238]
MBNL* (h.s., m.m.)	MI	Down	Protective	Cardiac myofibroblasts?	•Left coronary artery ligation-induced MI mouse model/Mbnl1 KO: Mbnl was required for preserving ventricular wall integrity after MI •Fibroblast-specific human MBNL1 expression caused heart fibrosis	[180]
QKI* (h.s. m.m.)	CAD	Up	Deleterious	VSMCs and macrophages?	•Vascular femoral-cuff-injury mouse model: hypomorphic Qki mutant showed reduced neointima and foam cell formation •Expression correlation in human and mouse vessel intima	[190] [193]
QKI* (h.s. m.m. d.r.)	MI	Down	Protective	Cardiomyocytes?	•I/R-induced MI in leptin-mutant diabetic mouse model: intramyocardial injected QKI resolved heart injury •Loss-of-function in zebrafish: Qki promoted myofibril formation •Human GWAs: SNPs near QKI associated with MI	[191,192] [187]
RBM20* (h.s, m.m. d.r., r.n.)	DCM	Down	Protective	Heart	•Mutation in rat: DCM-like heart phenotype and altered Titin splicing •Mouse KO: DCM-like heart phenotype and altered circTitin isoforms •Mutations human: associating with familial DCM	[239] [194] [195]

Abbreviations: CAD (coronary artery disease), ISO (isoproterenol), I/R (ischemia/reperfusion), T-cell (T-lymphocyte), PBMC (peripheral blood mononuclear cell), VSMC (vascular smooth muscle cell), GWAS (genome-wide association study), MI (myocardial infarction), LAD (left anterior descending artery), DCM (dilated cardiomyopathy), ER (endoplasmatic reticulum), CM (congenital myopathy), DM (myotonic dystrophy), KO (knockout), h.s. (homo sapiens), m.m. (mus musculus), d.r. (danio rerio), r.n. (rattus norvegicus).