title: Impact of Either GLP-1 Agonists or DPP-4 Inhibitors on Pathophysiology of Heart Failure.
abstract: Since diabetes mellitus (DM) is the most common cause of heart failure (HF), it is critically important to clarify whether incretin hormones including glucagon-like peptide-1 (GLP-1), which play an important role in blood glucose control, mediate cardioprotection. There are many lines of basic research evidence indicating that GLP-1 improves the pathophysiology of HF: In murine and canine HF models, either GLP-1 analogues or DPP-IV inhibitors improved cardiac functions. The first question that arises is how either GLP-1 analogues or DPP-IV inhibitors mediate cardioprotection. Cardiovascular diseases are tightly linked to impaired glucose tolerance (IGT): IGT is not only one of the causes of cardiovascular events but also the result of HF. Indeed, the treatment of IGT improved HF, showing that one of the mechanisms attributable to DPP-IV inhibitors is related to the improvement of IGT. Intriguingly, either DPP-IV inhibitors or GLP-1 analogues mediate cardioprotection even without IGT, suggesting two possible explanations: One is that GLP-1 analogues directly activate the prosurvival kinases, such as Akt and Erk1/2, and another is that DPP-IV inhibition increases cardioprotective peptides such as BNP and SDF-1α. The next question is whether cardioprotection is translated to clinical medicine. Small scale clinical trials proved their cardioprotective effects; however, several large scale clinical trials have not proved the beneficial effects of DPP-IV inhibitors. Taken together, GLP-1 analogues or DPP-IV inhibitors can mediate cardioprotection, however, what needs to be clarified is who mainly receives their benefits among the patients with cardiovascular diseases and/or DM.
authors.affiliation: Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center.
authors.forename: Ayako
authors.initials: A
authors.lastname: Takahashi
authors.forename: Madoka
authors.initials: M
authors.lastname: Ihara
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000378:metabolism / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000378:metabolism / Q000494:pharmacology; D004285:Dogs; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D051379:Mice; D057170:Translational Research, Biomedical
chemical_list: D001786:Blood Glucose; D002316:Cardiotonic Agents; D054873:Dipeptidyl-Peptidase IV Inhibitors; D054795:Incretins; D052216:Glucagon-Like Peptide 1