Peroxisome Proliferator-Activated Receptor-γ Is Critical to Cardiac Fibrosis

Table 2

Effects of PPAR ligands on diabetic related cardiac fibrosis.

Study model	Dose/duration/route	Major cardiac findings and conclusions	Ref.
Male OLETF rats, LETO rats, 20 weeks old	Rosiglitazone 20 mg/kg/d for 20 weeks, gavage	Suppression of RAGE and CTGF expression in the diabetic myocardium appears to contribute to the antifibrotic effect of rosiglitazone	[35]
Male STZ-induced diabetic Sprague-Dawley rats (200 ± 20 g)	Pioglitazone 10 mg/kg/d for 14 weeks, gavage	Activation of the PPAR signal pathway could repress cardiac fibrosis in diabetic rats and partly improve cardiac remodeling and function by downregulating activity of RAS level	[36]
Male offspring of Wistar rats fed NP diet or LP diet, 3 months old	Rosiglitazone 5 mg/kg/d for three months, gavage	Rosiglitazone showed beneficial effects on rat offspring programmed by low protein diet during gestation decreasing cardiac fibrosis and enhancing myocardial vascularization	[37]
Alloxan-induced diabetic rabbits 1.8–2.5 Kg	Rosiglitazone 2 mg/kg/d for 4 weeks, unclear	Rosiglitazone attenuates arrhythmogenic atrial structural remodeling and atrial fibrillation promotion	[38]
Male OLETF rats, LETO rats, 20 weeks old	Pioglitazone 10 mg/kg/d for 20 weeks, per orem	Activation of PPAR may decrease collagen concentration and reduce cardiac fibrosis by exerting regulatory effects on cardiac telomere biology	[39]
Male WT, CBS^+/+,  CBS^+/−, and Ins2^+/−/CBS^+/− rats, 20 weeks old	Ciglitazone 3 mg/kg/d for 4 weeks, orally	Treatment with ciglitazone alleviated MMP-9 activity and fibrosis and improved end diastolic diameter	[40]
Male OLETF rats, LETO rats, 28 weeks old	Rosiglitazone 3 mg/kg/d and losartan 5 mg/kg/d for 12 weeks, gavage	A combination of rosiglitazone and losartan attenuates myocardial fibrosis and dysfunction	[41]
Male diabetic hypertensive rats 179–219 g	Rosiglitazone 3 mg/kg/d or combination of felodipine 5 mg/kg/d for one month, orally	The combined treatment can improve dyslipidemia and decrease TNF, TGF, collagen I, and collagen III, and increased MMP-2 but within a greater effect than treatment with rosiglitazone alone	[28]

OLETF: Otsuka Long-Evans Tokushima Fatty, LETO: Long-Evans Tokushima Otsuka, RAGE: receptor for advanced glycation end products, CTGF: connective tissue growth factor, WT: wild type, CBS^+/−: cystathionine beta synthase mutant, Ins2^+/−: insulin 2 mutant, MMP: matrix metalloproteinases, TNF: tumor necrosis factor, TGF: transforming growth factor, NP: normal protein (19% protein), LP: low protein (5% protein), STZ: streptozotocin, and RAS: renin-angiotensin system.