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Novel Therapeutic Approaches Targeting the Renin-Angiotensin System and Associated Peptides in Hypertension and Heart

Lauren B Arendse1, A H Jan Danser1, Marko Poglitsch1

  • 1Department of Integrative Biomedical Sciences, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa (L.B.A., E.D.S.); Division of Pharmacology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands (A.H.J.D.); Attoquant Diagnostics, Vienna, Austria (M.P.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (R.M.T.); Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota (J.C.B.); Institut National de la Santé et de la Recherche Médicale, Paris, France (C.L.-C.); and Clinical Trials Group, Immune Tolerance Network, San Francisco, California (M.R.E.).

Pharmacological Reviews
|September 21, 2019
PubMed

Insights

Novel therapies targeting the renin-angiotensin system (RAS) offer improved cardiovascular protection. New drugs and gene therapy approaches aim to better control blood pressure and treat heart failure.

Area of Science:

  • Cardiovascular Pharmacology
  • Renal Physiology
  • Drug Development

Background:

  • Current renin-angiotensin system (RAS) blockade therapies (ACE inhibitors, AT1R blockers) show limitations in treating hypertension and cardiovascular diseases.
  • Understanding of RAS complexity and associated vasoactive pathways has revealed new therapeutic targets.
  • Novel strategies aim to modulate interconnected blood pressure-regulating pathways for enhanced efficacy.

Purpose of the Study:

  • To review emerging therapeutic strategies for hypertension and cardiovascular diseases targeting the RAS.
  • To highlight novel drug candidates and unconventional approaches in preclinical and early clinical development.
  • To explore methods for improved cardiovascular protection and blood pressure management.

Main Methods:

  • Focus on novel small molecule inhibitors and receptor agonists/antagonists.
  • Exploration of gene therapy for angiotensinogen suppression at the RNA level.
  • Investigation of recombinant ACE2 protein and novel bispecific designer peptides.

Main Results:

  • Emerging therapies show potential for improved cardiovascular protection and blood pressure control.
  • Dual-acting agents and combination therapies offer enhanced treatment efficacy.
  • Upregulation of the ACE2/angiotensin-(1-7)/Mas axis presents a counter-regulatory strategy.

Conclusions:

  • Advances in RAS research have opened new avenues for developing innovative drugs.
  • Novel therapeutic approaches hold promise for better treatment of hypertension and heart failure.
  • Targeting the RAS with new agents could lead to reduced adverse effects and improved patient outcomes.

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