Pathophysiology and therapeutic potential of cardiac fibrosis

Hara, Hironori; Takeda, Norifumi; Komuro, Issei

doi:10.1186/s41232-017-0046-5

Inflammation and Regeneration

Table 2 Growth factors, transcription factors, microRNAs, and small molecules that stimulate CM replication

From: Pathophysiology and therapeutic potential of cardiac fibrosis

		Models/treatments		Species	Age or weight/cells	Follow-up	Markers of proliferation	Functional improvements comments	References
Factors	Neuregulin 1	In vitro		Rat	ARCM		BrdU, Aurora B		[57]
		In vivo	IP injection	Mouse	12 weeks	9 days	BrdU, pH3, Aurora B
		MI	IP injection after MI	Mouse	8 weeks	14 weeks	BrdU, pH3, Aurora B	EF, scar size
	Periostin	In vitro		Rat	ARCM		BrdU, Aurora B		[58]
		In vivo	Injection into the myocardium	Rat	300 g	7 days	BrdU, Aurora B
		MI	Gelfoam patches to epicardial after MI	Rat	300 g	12 weeks	BrdU, Aurora B (1 and 12 weeks)	EF, FS, scar size
	Oncostatin M	In vitro		Rat	NRCM		EdU		[59]
	Oncostatin M	MI	IP injection after MI	Mouse	12 weeks	21 days		survival, EF	[59]
	Salvador (Salv)	In vivo	NKX 2.5-Cre; Salv ^flox/flox (Salv CKO)	Mouse	E12.5, P2		pH3 (E12.5)	Thickened ventricular walls, enlarged ventricular chambers	[60]
	Yes-associated protein (Yap)	In vivo	αMHC-YapS112A	Mouse	P28	21 days	pH3, Aurora B (7 days)	FS, scar size (21 days)	[61]
	Yes-associated protein (Yap)	In vivo	αMHC-rtTA; Yap, induction by doxycycline	Mouse	8 weeks	5 weeks	EdU, pH3	EF, scar size	[62]
	Yes-associated protein (Yap)	In vivo	AAV9-cTnT-hYap injection into the myocardium	Mouse	10–12 weeks	23 weeks	EdU (5 days)	FS (4 weeks), survival (23 weeks)	[62]
miRNAs	miR-15 family	In vivo	anti-miR-15/16 s.c. injection	Mouse	P2	10 days	pH3		[63]
	miR-15 family	I/R	anti-miR-15 s.c. injection before I/R	Mouse	P21	21 days	pH3 (7 days)	FS (21 days)	[37]
	miR-590, miR-199a	In vitro	Transfection	Rat/Mouse	ARCM, NRCM, NMCM		Ki67, EdU, pH3, Aurora B		[64]
		In vivo	hsa-miR-590-3p or hsa-miR-199a-3p injection into the myocrdium	Rat	P0	4 days	EdU
		In vivo	AAV9-miR-590 or AAV9-miR-199a IP injection	Mouse	P0	12 days	pH3
		MI	AAV9-miR-590 or AAV9-miR-199a IP injection after MI	Mouse	8–12 weeks	60 days	EdU	EF, FS, scar size
	miR-222	In vitro	Transfection	Rat	NRCM		Ki67, EdU		[65]
	miR-222	I/R	αMHC-tTA; miR-222 induction by doxycycline deprivation before I/R	Mouse	10–12 weeks	6 weeks	EdU. pH3	FS, scar size	[65]
	miR-17-92 family	In vitro	Transfection	Rat	NRCM		EdU, Aurora B		[66]
		In vivo	NKX 2.5-Cre; miR-17–92	Mouse	E16.5, P4		pH3
		In vivo	αMHC-Cre; miR-17–92	Mouse	P15		EdU, pH3, Aurora B
		MI	αMHC-MerCreMer; miR-17–92 induction by tamoxifen after MI	Mouse	2 months	4 months	EdU	FS, scar size
Small molecule	BIO	In vitro		Rat	NRCM		BrdU, pH3		[67]

AAV adeno-associated virus, ARCM adult rat cardiomyocytes, BrdU, 5-bromo-2′-deoxyuridine, EdU 5-ethynyl-2′-deoxyuridine, EF ejection fraction, FS fractional shortening, IP intraperitoneal, I/R Ischemia/reperfusion, MI myocardial infarction, NMCM neonatal mouse cardiomyocytes, NRCM neonatal rat cardiomyocytes, pH3 Phospho-Histone H3; s.c. subcutaneous

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ISSN: 1880-8190

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