Key result
Continuous infusion of Resolvin D2 in mice with Ang-II-induced hypertension attenuated blood pressure increases but exacerbated Ang-II-induced intracardiac artery fibrosis.
Why the study?
Specialized pro-resolving mediators regulate inflammation resolution relevant to cardiac and vessel remodeling, but the effect of Resolvin D2 on hypertension and cardiac remodeling required investigation.
Does continuous infusion of Resolvin D2 affect blood pressure and cardiac remodeling in a mouse model of Ang-II-induced hypertension?
Does continuous infusion of Resolvin D2 affect blood pressure and cardiac remodeling in a mouse model of Ang-II-induced hypertension?
Continuous infusion of Resolvin D2 in Ang-II hypertensive mice attenuates blood pressure increases but paradoxically exacerbates intracardiac artery fibrosis, suggesting this administration route is suboptimal.
RvD2 shows mixed effects on BP and remodeling in Ang-II mice; leaves open net therapeutic value pending targeted studies.
Specialized pro-resolving mediators (SPMs) are key effectors of resolution of inflammation. This is highly relevant for cardiac and vessel remodeling, where the net inflammatory response contributes to determine disease outcome. Herein, we used a mice model of angiotensin (Ang)-II-induced hypertension to study the effect of the SPM Resolvin D2 (RvD2), on hypertension and cardiac remodeling. By using subcutaneous osmotic minipumps, mice were treated with PBS or Ang-II in combination with or without RvD2 for two weeks. Mice receiving RvD2 gained less blood pressure increase compared to Ang-II alone. Surprisingly, however, examination of intracardiac arteries revealed that RvD2 treatment in combination with Ang-II exacerbated Ang-II-induced fibrosis. Measures of vascular smooth muscle cell dedifferentiation correlated with the level of vascular remodeling, indicating that this dedifferentiation, including increased proliferation and migration, is a contributing factor. RNA sequencing of left ventricle cardiac tissue supported these findings as pathways related to cell proliferation and cell differentiation were upregulated in mice treated with Ang-II in combination with RvD2. Additionally, the RNA sequencing also showed upregulation of pathways related to SPM metabolism. In line with this, Mass spectrometry analysis of lipid mediators showed reduced cardiac levels of the arachidonic acid derived metabolite leukotriene E4 in RvD2 treated mice. Our study suggests that continuous infusion through osmotic minipumps should not be the recommended route of RvD2 administration in future studies.
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Olsen et al. (2024) studied Angiotensin-II-induced hypertension. Resolvin D2 (RvD2) in combination with Ang-II vs. PBS or Ang-II alone was evaluated on Blood pressure and intracardiac artery remodeling. Continuous infusion of Resolvin D2 in mice with Ang-II-induced hypertension attenuated blood pressure increases but exacerbated Ang-II-induced intracardiac artery fibrosis.
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