Down-regulation of cardiac apelin system in hypertrophied and failing hearts: Possible role of angiotensin II-angiotensin type 1 receptor system

J Mol Cell Cardiol. 2006 Nov;41(5):798-806. doi: 10.1016/j.yjmcc.2006.07.004. Epub 2006 Aug 17.


Cardiac apelin has recently been suggested to contribute to the pathophysiology of heart failure (HF) in humans. In animal experiments, its infusion acutely improved systolic as well as diastolic LV function. Although its deficit could critically determine the cardiac dysfunction, its regulatory mechanism is unknown. Accordingly, we investigated the role and regulation of the cardiac apelin system in the diseased heart using Dahl salt-sensitive rats, which show a distinctive transition from compensatory LV hypertrophy (LVH) to HF. In the compensatory LVH stage, apelin and its receptor APJ mRNA showed no change compared with control animals, while these were markedly down-regulated in the HF stage (72% and 57% decrease, respectively). The rats were chronically treated with telmisartan (angiotensin type 1 receptor blocker [ARB], 5 mg/kg/day, n=9), ONO-4817 (matrix metalloproteinase [MMP] inhibitor, 200 mg/kg/day, n=9), bisoprolol (beta blocker, 3 mg/kg/day, n=6) or vehicle (0.5%CMC, n=9) from the LVH stage. Although the functional improvements were similar among the three treated groups 6 weeks after treatment, restoration of cardiac apelin and APJ expression was observed only in the ARB group. Furthermore, in angiotensin II-infused rats, cardiac apelin mRNA was decreased after 24 h of treatment and its restoration was achieved by treatment with ARB. These results indicate that the cardiac apelin system is markedly down-regulated in experimental HF and may be regulated by the angiotensin II-angiotensin type 1 receptor system directly. Inhibition of the renin-angiotensin system may have beneficial effects, at least in part, through restoration of the cardiac apelin system in the treatment of HF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Animals
  • Apelin
  • Cardiomegaly / blood*
  • Cardiomegaly / chemically induced
  • Cardiomegaly / therapy
  • Carrier Proteins / metabolism*
  • Down-Regulation
  • Heart Failure / blood*
  • Heart Failure / chemically induced
  • Heart Failure / therapy
  • Intercellular Signaling Peptides and Proteins
  • Male
  • RNA, Messenger / metabolism*
  • Rats
  • Rats, Inbred Dahl
  • Receptor, Angiotensin, Type 1 / physiology*
  • Signal Transduction


  • Angiotensin II Type 1 Receptor Blockers
  • Apelin
  • Apln protein, rat
  • Carrier Proteins
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Receptor, Angiotensin, Type 1
  • Angiotensin II