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A complex role for the progesterone receptor in the response to vascular injury

R H Karas1, M van Eickels, J P Lydon

  • 1Molecular Cardiology Research Institute, New England Medical Center Hospitals Inc., Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

The Journal of Clinical Investigation
|August 24, 2001
PubMed

Insights

The progesterone receptor (PR) plays a direct role in regulating vascular injury response and smooth muscle cell proliferation. PR knockout mice show worsened vascular hypertrophy and cell growth compared to wild-type mice.

Area of Science:

  • Vascular Biology
  • Endocrinology
  • Cardiovascular Research

Background:

  • Hormone replacement therapy research highlights the cardiovascular effects of progestins.
  • The in vivo role of the progesterone receptor (PR) in vascular biology remains largely uncharacterized.

Purpose of the Study:

  • To investigate the in vivo role of the progesterone receptor (PR) in vascular smooth muscle cell (VSMC) proliferation and response to injury.
  • To elucidate the direct effects of progesterone on vascular health via PR signaling.

Main Methods:

  • Utilized ovariectomized female PR knockout (PRKO) mice and wild-type (WT) littermates in a mouse carotid artery injury model.
  • Assessed vascular medial hypertrophy and VSMC proliferation in response to injury.
  • Cultured VSMCs from PRKO and WT mice, with and without progesterone treatment, and employed adenoviral methods for PR reintroduction.

Main Results:

  • PRKO mice exhibited significantly greater vascular medial hypertrophy and VSMC proliferation post-injury compared to WT mice.
  • Progesterone did not affect PRKO mice but exacerbated injury response in WT mice.
  • Cultured PRKO VSMCs were hyperproliferative and unresponsive to progesterone, while WT VSMCs showed inhibited proliferation with progesterone, which was restored by PR reintroduction.

Conclusions:

  • The progesterone receptor (PR) has a direct role in regulating vascular injury response and VSMC proliferation.
  • The effects of PR and progesterone on VSMCs differ significantly between in vitro and in vivo settings.
  • These findings underscore the importance of PR in maintaining vascular homeostasis and suggest differential PR signaling in cultured cells versus intact vessels.

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