Table 5.

Effects of trientine on myocardial interstitial fibrosis and extracellular matrix in human and animal studies.

Study	Type of Model/Subjects	Trientine (TETA) (Dose and Duration)	Findings	Reference
Animal	STZ-induced diabetic cardiomyopathy in rats	8–11 mg/day in drinking water for 7 weeks (post-treatment)	↓ LV collagen I ↓ LV collagen III	[39]
Animal	STZ-induced diabetic cardiomyopathy in rats	20 mg/day in drinking water for 8 weeks (post-treatment)	↓ LV collagen I, III, and IV mRNA ↓ LV fibronectin-I mRNA ↓ LV PAI-1 mRNA ↓ LV TGF-β1 mRNA ↓ LV Smad4 mRNA	[42]
Animal	Transverse aortic constriction- induced cardiac hypertrophy in rats	21.9 and 87.6 mg/kg twice daily orally for 6 weeks	TETA (21.9 mg/kg/day): ↓ cardiac collagen I TETA (87.6 mg/kg/day): ↔ cardiac collagen I	[14]
Animal	STZ-induced diabetic cardiomyopathy in rats	30 mg/day in drinking water for 8 weeks (post-treatment)	↓ LV collagen I ↔ LV collagen III	[33]
Animal	STZ-induced diabetic cardiomyopathy in rats	20 mg/day in drinking water for 8 weeks (post-treatment)	↓ TGF-β1	[25]
Animal	Ascending aortic constriction-induced cardiac hypertrophy in rats	21.9 mg/kg twice daily orally for 6 weeks	↓ cardiac collagen volume fraction ↓ cardiac hydroxyproline ↔ cardiac collagen I ↓ cardiac collagen III ↔ cardiac active MMP-9 ↓ cardiac MMP-9 mRNA ↑ cardiac active MMP-2 ↔ cardiac MMP-2 mRNA ↓ cardiac TIMP-1 mRNA ↓ cardiac TIMP-2 mRNA	[15]
Human	Patients with hypertrophic cardiomyopathy (n = 20)	300 mg twice daily orally, increased after 1 week to 600 mg twice daily if tolerated for 6 months	↔ ECV fraction ↓ ECM volume	[23]

ECM, extracellular matrix; ECV, extracellular volume; MMP, matrix metalloproteinases; LV, left ventricle; PAI-1, plasminogen activator inhibitor-1; Smad4, small mothers against decapentaplegic; STZ, streptozotocin; TGF-β1 transforming growth factor-β1; TIMP, tissue inhibitor of metalloproteinase; ↑, significant increase; ↓, significant decrease; ↔, no difference.