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<p>This study investigates the effects of BI 1,029,539 (GS-248 or Vipoglanstat), a novel selective inhibitor of human microsomal prostaglandin E synthase-1 (mPGES-1), in experimental models of myocardial infarction and vascular injury using transgenic mice constitutively expressing the humanized mPGES-1 (Ptges) allele. Coronary artery occlusion was induced in mice randomized to receive vehicle, BI 1,029,539, or celecoxib either one week prior to (pre-treatment) or one week after (post-treatment) coronary artery occlusion. Wire-induced vascular injury was performed in mice randomized to receive vehicle or BI 1,029,539, and carotid arterial smooth muscle cell outgrowth was assessed ex vivo using explant cultures. Pre- and post-treatment with BI 1,029,539 did not affect mortality but significantly attenuated myocardial hypertrophy and improved left ventricular function compared to vehicle controls. In contrast, treatment with the COX-2 inhibitor, celecoxib, during the post-infarction period was associated with increased mortality. Additionally, BI 1,029,539 inhibited carotid artery smooth muscle cell migration and proliferation in explant cultures and reduced neointima formation in response to wire-induced vascular injury. These findings demonstrate a favorable cardiovascular profile for BI 1,029,539, a selective inhibitor of human mPGES-1, in experimental models of myocardial infarction and vascular injury. The results suggest its potential therapeutic benefits in mitigating cardiovascular risks.</p>

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Characterization of a new specific mPGES-1 inhibitor in cardiovascular system

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月24日

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  • Xinchun Lin,
  • Huiying Feng,
  • Jin-Rui Zhang,
  • Malarvizhi Gurusamy,
  • Saeed Nasseri,
  • Anton Pekcec,
  • Dongmei Wu

摘要

This study investigates the effects of BI 1,029,539 (GS-248 or Vipoglanstat), a novel selective inhibitor of human microsomal prostaglandin E synthase-1 (mPGES-1), in experimental models of myocardial infarction and vascular injury using transgenic mice constitutively expressing the humanized mPGES-1 (Ptges) allele. Coronary artery occlusion was induced in mice randomized to receive vehicle, BI 1,029,539, or celecoxib either one week prior to (pre-treatment) or one week after (post-treatment) coronary artery occlusion. Wire-induced vascular injury was performed in mice randomized to receive vehicle or BI 1,029,539, and carotid arterial smooth muscle cell outgrowth was assessed ex vivo using explant cultures. Pre- and post-treatment with BI 1,029,539 did not affect mortality but significantly attenuated myocardial hypertrophy and improved left ventricular function compared to vehicle controls. In contrast, treatment with the COX-2 inhibitor, celecoxib, during the post-infarction period was associated with increased mortality. Additionally, BI 1,029,539 inhibited carotid artery smooth muscle cell migration and proliferation in explant cultures and reduced neointima formation in response to wire-induced vascular injury. These findings demonstrate a favorable cardiovascular profile for BI 1,029,539, a selective inhibitor of human mPGES-1, in experimental models of myocardial infarction and vascular injury. The results suggest its potential therapeutic benefits in mitigating cardiovascular risks.