Gene therapy for hypertension

Expert Opin Biol Ther. 2017 Nov;17(11):1345-1361. doi: 10.1080/14712598.2017.1364726. Epub 2017 Aug 17.

Abstract

The control of hypertension and the resulting cardiovascular events is still insufficient. Thus, the search for novel means for blood pressure (BP) reduction remains worth further clinical and research attention. The advances in vector and construct design sketch the use of gene therapy in hypertension. Areas covered: We have searched for studies using gene therapy in hypertension reporting BP outcomes. We have identified 63 experimental studies demonstrating feasible targeting of the classical and new renin-angiotensin-aldosterone system, β1-adrenergic receptor, NO-cGMP axis, endothelin, natriuretic peptides, kallikrein system, cytochrome P-450 hydroxylase, oncogenes, growth factors, interleukins, angiopoietin-1, adrenomedullin or Klotho in small rodents. Expert opinion: The usual BP reduction was by 10-30 mmHg for up to several months. Some studies reported target organ damage attenuation or even survival prolongation. However, the concept did not reach the clinical phase, in contrast to other cardiovascular conditions. Increased gene transfection efficacy necessary for a systemic treatment, personalized identification of the implied aetiology from the multifactorial background and evidence from larger mammals are required for gene therapy to compete with the broad spectrum of current therapeutic options in hypertension. Until then, in the field of hypertension, gene modulation will provide a valuable research tool.

Keywords: Gene therapy; NO-synthase; RNA interference; adeno-associated virus; adenovirus; arterial hypertension; kallikrein; natriuretic peptides; renin-angiotensin-aldosterone system; vector.

Publication types

  • Review

MeSH terms

  • Angiopoietin-1 / genetics
  • Angiopoietin-1 / metabolism
  • Animals
  • Blood Pressure
  • Cytochrome P-450 CYP4A / genetics
  • Cytochrome P-450 CYP4A / metabolism
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism
  • Genetic Therapy
  • Hypertension / genetics
  • Hypertension / therapy*
  • Kallikrein-Kinin System / genetics
  • Receptors, Adrenergic / genetics
  • Receptors, Adrenergic / metabolism
  • Renin-Angiotensin System / genetics

Substances

  • Angiopoietin-1
  • Endothelin-1
  • Receptors, Adrenergic
  • Cytochrome P-450 CYP4A