Egg ovotransferrin‐derived ACE inhibitory peptide IRW increases ACE2 but decreases proinflammatory genes expression in mesenteric artery of spontaneously hypertensive rats

• Published in: Molecular nutrition & food research 2015-09, Vol.59 (9), p.1735-1744
• Main Authors: Majumder, Kaustav, Liang, Guanxiang, Chen, Yanhong, Guan, LeLuo, Davidge, Sandra T, Wu, Jianping
• Format: Article
• Language: English
• Subjects: ACE-2; Angiotensin-Converting Enzyme Inhibitors - pharmacology; animal disease models; Animals; Antihypertensive Agents - pharmacology; antihypertensive effect; ATP Binding Cassette Transporter, Sub-Family B - genetics; ATP Binding Cassette Transporter, Sub-Family B - metabolism; Bioactive peptides; Blood Pressure; Cdh1 Proteins - genetics; Cdh1 Proteins - metabolism; Conalbumin - pharmacology; Databases, Genetic; eggs; gene expression; Gene Expression Regulation; genes; Hypertension; inflammation; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; interferon regulatory factor-8; Interferon Regulatory Factors - genetics; Interferon Regulatory Factors - metabolism; kidneys; mesenteric arteries; Mesenteric Arteries - drug effects; Mesenteric Arteries - metabolism; Peptides - chemistry; Peptides - pharmacology; peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; quantitative polymerase chain reaction; Rats; Rats, Inbred SHR; RNA; RNAseq; Sequence Analysis, RNA; SHR; transcriptomics; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism; vasodilation
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201500050

SCOPE: Egg ovotransferrin‐derived angiotensin converting enzyme (ACE) inhibitory peptide IRW was previously shown to reduce blood pressure in spontaneously hypertensive rats through reduced vascular inflammation and increased nitric oxide‐mediated vasorelaxation. The main objective of the present study was to investigate the molecular mechanism of this peptide through transcriptome analysis by RNAseq technique. METHODS AND RESULTS: Total RNA was extracted from kidney and mesenteric arteries; the RNAseq libraries (from untreated and IRW‐treated groups) were constructed and subjected to sequence using HiSeq 2000 system (Illumina) system. A total of 12 764 and 13 352 genes were detected in kidney and mesenteric arteries, respectively. The differentially expressed (DE) genes between untreated and IRW‐treated groups were identified and the functional analysis through ingenuity pathway analysis revealed a greater role of DE genes identified from mesenteric arteries than that of kidney in modulating various cardiovascular functions. Subsequent qPCR analysis further confirmed that IRW significantly increased the expression of ACE‐2, ABCB‐1, IRF‐8, and CDH‐1 while significantly decreased the expression ICAM‐1 and VCAM‐1 in mesenteric arteries. CONCLUSION: Our research showed for the first time that ACE inhibitory peptide IRW could contribute to its antihypertensive activity through increased ACE2 and decreased proinflammatory genes expression.