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Prostacyclin protects against elevated blood pressure and cardiac fibrosis

Helene Francois1, Krairerk Athirakul, David Howell

  • 1Department of Medicine, Duke University and Durham VA Medical Centers, Durham, North Carolina 27705.

Cell Metabolism
|September 13, 2005
PubMed

Insights

Mice lacking the prostacyclin (PGI2) receptor developed hypertension and cardiac damage. Blocking the thromboxane A2 (TxA2) receptor prevented cardiac issues, suggesting therapies targeting TxA2 may protect patients on COX-2 inhibitors.

Area of Science:

  • Cardiovascular Science
  • Pharmacology
  • Renal Physiology

Background:

  • Specific cyclooxygenase-2 (COX-2) inhibitors are linked to cardiovascular risks.
  • These drugs decrease prostacyclin (PGI2) while sparing thromboxane A2 (TxA2) production.
  • The impact of this eicosanoid imbalance on hypertension development is unknown.

Purpose of the Study:

  • To investigate the role of the prostacyclin (PGI2) receptor in hypertension and cardiovascular complications.
  • To determine the effects of combined prostacyclin (PGI2) and thromboxane A2 (TxA2) receptor deletion on cardiovascular outcomes.

Main Methods:

  • Utilized genetically engineered mice lacking the prostacyclin (PGI2) receptor (IPKOs).
  • Assessed cardiovascular parameters including blood pressure, cardiac hypertrophy, and fibrosis.
  • Generated and analyzed double knockout mice lacking both prostacyclin (PGI2) and thromboxane A2 (TxA2) receptors (IPTP DKOs).

Main Results:

  • Mice lacking the prostacyclin (PGI2) receptor (IPKOs) exhibited salt-sensitive hypertension, cardiac hypertrophy, and severe cardiac fibrosis.
  • Deletion of the thromboxane A2 (TxA2) receptor in double knockouts (DKOs) did not prevent hypertension.
  • Cardiac hypertrophy was ameliorated, and fibrosis was prevented in IPTP double knockouts (DKOs).

Conclusions:

  • Prostacyclin (PGI2) receptor deficiency unmasks adverse cardiovascular effects of thromboxane A2 (TxA2).
  • Targeting thromboxane A2 (TxA2) may offer cardioprotection against end-organ damage in patients using COX-2 inhibitors.
  • Adjuvant therapies blocking TxA2 actions could be beneficial without impacting blood pressure control.

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