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Chronic treatment with apelin, losartan and their combination reduces myocardial infarct size and improves cardiac

Elham Abbasloo1, Hamid Najafipour2, Abedin Vakili3

  • 1Physiology, Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.

Clinical and Experimental Pharmacology & Physiology
|October 21, 2019
PubMed

Insights

Combining apelin with losartan (an AT1R antagonist) significantly reduces heart damage from ischaemia-reperfusion injury. This combination therapy offers greater protection than either treatment alone by lowering angiotensin type 1 receptor expression.

Area of Science:

  • Cardiovascular Research
  • Pharmacology
  • Myocardial Infarction Pathophysiology

Background:

  • The renin-angiotensin system (RAS) negatively impacts the ischaemic heart, while the apelin/APJ system offers protection.
  • The interaction between RAS and apelin/APJ systems in myocardial infarction (MI) pathophysiology requires further elucidation.

Purpose of the Study:

  • To investigate the protective effects of chronic apelin, losartan, and their combination against ischaemia-reperfusion (IR) injury in a rat heart model.
  • To assess the impact of these treatments on the expression of apelin-13 receptor (APJ) and angiotensin type 1 receptor (AT1R) in the myocardium.

Main Methods:

  • Rats were pretreated for 5 days with saline, apelin-13, an apelin antagonist, losartan, or a combination of apelin and losartan.
  • Ischaemia-reperfusion (IR) injury was induced using a Langendorff isolated heart perfusion system with left anterior descending artery occlusion followed by reperfusion.
  • Infarct size and left ventricular function (LVDP, LVEDP, RPP) were measured, alongside myocardial APJ and AT1R protein levels.

Main Results:

  • Apelin, losartan, and their combination significantly reduced infarct size by approximately 30%, 33%, and 48%, respectively.
  • All tested pretreatments significantly improved left ventricular function indices.
  • Ischaemia-reperfusion increased AT1R protein levels, which were subsequently reduced by apelin, losartan, and combination treatments; APJ levels remained largely unchanged.

Conclusions:

  • Chronic pretreatment with apelin and losartan demonstrates significant cardioprotective effects against IR injury.
  • Combination therapy of apelin and losartan provides enhanced protection compared to monotherapy, likely through reducing AT1R expression.
  • This combination strategy holds potential for mitigating IR-induced heart damage in patients with coronary artery disease at risk of MI and reperfusion injury.

Keywords:
angiotensin receptorsangiotensin type 1 receptorsapelin receptorsheart resistanceinfarct sizeischaemia-reperfusion injurymyocardium

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