Bioactive peptides attenuate cardiac hypertrophy and fibrosis in spontaneously hypertensive rat hearts

Chih Yang Huang ^a,b,c,d,e, Srinivasan Nithiyanantham ^a, Jia Ying Liao ^f, Wan Teng Lin ^f,*

a Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan

b Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

c Department of Biotechnology, Asia University, Taichung, Taiwan

d Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan

e Cardiovascular and Mitochondrial Related Diseases Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

f Department of Hospitality Management, College of Agriculture, Tunghai University, Taichung, Taiwan

Alcalase potato protein hydrolysate (APPH), a nutraceutical food, might an have important role in anti-obesity activity. Recent studies from our lab indicated that APPH treatment had lipolysis stimulating activity and identified was an efficient anti-obesity diet ingredient. In this study we aim to investigate the beneficial effects of pure peptide amino acid sequences (DIKTNKPVIF (DI) and IF) from APPH supplement in the regulation of cardiac hypertrophy and fibrosis on spontaneously hypertensive rats (SHR). We examined hematoxylin and eosin staining, Masson's trichrome staining, echocardiographic parameters, serum parameters, hypertrophy, inflammation and fibrotic marker expression to demonstrate efficacy of bioactive peptides in a SHR model. There was a significant upregulation between SHR and bioactive peptides treated groups in left heart weight (LHW), LHW/WHW, LHW/Tibia, LVIDd, and LVd mass. In addition, the bioactive peptides repress the protein expression of hypertrophy markers (BNP, MYH7), inflammation (TLR-4, p-NFkB, TNF-α, IL-6), and fibrotic markers (uPA, MMP-2, TIMP1, CTGF). In summary, these results indicate that DI and IF bioactive peptides from APPH attenuate cardiac hypertrophy, inflammation and fibrosis in the SHR model.

Keywords: Bioactive polypeptides; Fibrosis; Hypertrophy; SHR rats; Inflammation