Angiotensin II reduces membranous angiotensin-converting enzyme 2 in pressurized human aortic endothelial cells

J Renin Angiotensin Aldosterone Syst. 2009 Dec;10(4):210-5. doi: 10.1177/1470320309343710. Epub 2009 Aug 28.


Introduction: We applied pressure stress to human aortic endothelial cells (HAEC) and investigated whether mechanical pressure stress and/or angiotensin II (Ang II) affected angiotensin-converting enzyme (ACE) 2. We then tested whether the administration of nifedipine had a demonstrable and possibly beneficial effect.

Methods: A pulsatile atmospheric pressure with or without Ang II was loaded on HAECs. The expression of ACE2 was studied by immunoblots and reverse transcription/real-time polymerase chain reaction.

Results: The pulsatile mechanical pressure increased the expression of ACE2 mRNA by approximately 80%. Supplementation of Ang II (1 microM) with pulsatile mechanical pressure decreased the expression of ACE2 mRNA by approximately 54%. Pulsatile atmospheric pressure increased ACE2 protein, but supplementation of Ang II (1 microM) also increased ACE2 protein, and the latter failed to show significant change compared to pressurized control without Ang II. Ang II administration reduced ACE2 protein in the membranous fraction under pressurized condition. Administration of nifedipine (1 microM) protected cells from this ACE2 protein reduction at the HAEC membrane.

Conclusions: These results indicate that pulsatile mechanical pressure and Ang II affect ACE2 in HAECs. Our findings suggest that blood pressure reduction with a calcium channel blocker is beneficial for the conservation of ACE2, and may provide a potential therapeutic target beyond blood pressure lowering in hypertensive patients.

MeSH terms

  • Angiotensin II / pharmacology*
  • Angiotensin-Converting Enzyme 2
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology*
  • Humans
  • Nifedipine / pharmacology*
  • Peptidyl-Dipeptidase A / biosynthesis*
  • Peptidyl-Dipeptidase A / drug effects
  • RNA, Messenger / metabolism
  • Stress, Mechanical


  • RNA, Messenger
  • Angiotensin II
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Nifedipine