title: DPP4 deficiency preserved cardiac function in abdominal aortic banding rats.
abstract: Dipeptidyl peptidase-4 (DPP4) enzyme inhibition has been reported to increase plasma glucagon-like peptide-1 (GLP-1) level for controlling postprandial glucose concentration. A prominent GLP-1 level in DPP4-deficient rats contributed to the resistance of endotoxemia and myocardial infarction. DPP4 deficiency also increased the capability against H₂O₂-induced stress in cardiomyocyte. However, long term effect of loss DPP4 activity on cardiac performance remained unclear. We used abdominal aortic banding (AAB) to induce pressure overload in wild-type and DPP4-deficient rats, and investigated the progression of heart failure. Cardiac histology and function were determined. Blood sample was collected for the plasma biochemical marker measurement. Heart weight to body weight ratio increased 1.2-fold after 6 weeks of AAB surgery. Cardiac function was compensated against pressure overload after 6 weeks of AAB surgery, but progressed to deterioration after 10 weeks of AAB surgery. AAB induced cardiac dysfunction was alleviated in DPP4-deficient rats. DPP4 activity increased significantly in wild-type rats after 10 weeks of AAB surgery, but remained unchanged in DPP4-deficient rats. In contrast, GLP-1 concentration was elevated by AAB after 6 weeks of surgery in DPP4-deficient rats, and remained high after 10 weeks of surgery. Ang II level markedly increased after 6 weeks of AAB surgery, but were less in DPP4-deficient rats. Massive collagen deposits in wild-type rat hearts appeared after 10 weeks of AAB surgery, which were alleviated in DPP4-deficient rats. Long term deficiency of DPP4 activity improved cardiac performance against pressure overload in rat, which may be attributed to a great quantity of GLP-1 accumulation during AAB.
authors.affiliation: Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Ku
authors.affiliation: Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ming-Jai
authors.initials: MJ
authors.lastname: Su
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology* / Q000503:physiopathology* / Q000601:surgery; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000172:deficiency* / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006334:Heart Function Tests; D006439:Hemodynamics; D008297:Male; D011312:Pressure; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D000804:Angiotensin II; D052216:Glucagon-Like Peptide 1; D003094:Collagen; D018819:Dipeptidyl Peptidase 4