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Prevention of atherosclerosis by specific AT1-receptor blockade with candesartan cilexetil

Vasilios Papademetriou1, Philippe Mammillot2, Robert Redman2

  • 1The Va Medical Center and Georgetown University and the George Washington University Washington D.C. USA, papavip@ aol.com.

Journal of the Renin-Angiotensin-Aldosterone System : JRAAS
|January 18, 2017
PubMed

Insights

The renin-angiotensin-aldosterone system (RAAS) blocker candesartan significantly reduced atherosclerosis and cholesterol buildup in rabbits. It also inhibited oxidized LDL uptake by macrophages, suggesting a role in preventing vascular disease.

Area of Science:

  • Cardiovascular Research
  • Pharmacology
  • Atherosclerosis Research

Background:

  • Blockade of the renin-angiotensin-aldosterone system (RAAS) shows potential in preventing atherosclerosis and vascular events.
  • The exact mechanisms by which RAAS blockade exerts its protective effects remain incompletely understood.

Purpose of the Study:

  • To investigate the efficacy of candesartan, an AT1-receptor blocker, in preventing atherosclerosis in Watanabe heritable hyperlipidaemic (WHHL) rabbits.
  • To determine the impact of AT1-receptor blockade on the uptake of oxidised low-density lipoprotein (oxLDL) by macrophages.

Main Methods:

  • WHHL rabbits were divided into three groups: placebo, atenolol, and candesartan, and treated for six months.
  • Macrophage cell cultures were used to assess the effect of candesartan on oxLDL uptake.

Main Results:

  • Candesartan treatment led to a significant 50-60% reduction in atherosclerotic plaque formation and a 66% decrease in thoracic aorta cholesterol accumulation compared to placebo and atenolol groups.
  • In macrophage cultures, candesartan demonstrated a dose-dependent inhibition of oxLDL uptake, achieving up to 70% inhibition at 5.6 µg/ml.

Conclusions:

  • AT1-receptor blockade with candesartan effectively reduces atherosclerosis and cholesterol accumulation in WHHL rabbits.
  • Candesartan's ability to inhibit oxLDL uptake by macrophages suggests a novel mechanism for its atheroprotective effects.
  • Further research in animal models and human trials is recommended to fully elucidate the role of AT1-receptor blockade in atherosclerosis prevention.
Keywords:
angiotensin II receptor antagonistantihypertensivediabeteshypertensionlisinoprilrenoprotectiontelmisartan

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