What question did this study set out to answer?

To identify key chemokine receptors driving vascular macrophage infiltration during deoxycorticosterone acetate (DOCA)/salt-induced hypertension and determine whether their pharmacological blockade reverses high blood pressure and vascular inflammation.

October 2, 2012HypertensionOpen Access

Reversal of Vascular Macrophage Accumulation and Hypertension by a CCR2 Antagonist in Deoxycorticosterone/Salt-Treated Mice

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Authors

CCChristopher T. ChanUniversity Health Network JMJeffrey P. MooreAstraZeneca (United Kingdom)KBKlaudia BudzynDiscovery Institute

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Implication

Animal study demonstrates that a CCR2 antagonist reduces vascular macrophage accumulation and blood pressure in hypertensive mice, suggesting chemokine receptor blockade can treat hypertension.

Key Points

To identify key chemokine receptors driving vascular macrophage infiltration during deoxycorticosterone acetate (DOCA)/salt-induced hypertension and determine whether their pharmacological blockade reverses high blood pressure and vascular inflammation.
Treated mice with DOCA/salt for 21 days to induce hypertension and screened aortic chemokine receptor expression using a 20-receptor gene array and real-time PCR.
Quantified aortic macrophage infiltration (CD45(+) CD11b(+) F4/80(+) cells) via flow cytometry.
Administered the CCR2 antagonist INCB3344 (30 mg/kg per day, intraperitoneally) beginning 10 days after DOCA/salt induction to evaluate therapeutic efficacy.
DOCA/salt treatment significantly raised systolic blood pressure (158 ± 2 mm Hg vs. 114 ± 5 mm Hg in sham controls; P<0.0001) and caused >2-fold upregulation of CCR2 mRNA alongside its ligands CCL2, CCL7, CCL8, and CCL12 (P<0.05).
Hypertensive mice exhibited a 2.9-fold increase in aortic wall macrophage infiltration compared to sham mice.
Delayed intervention with INCB3344 suppressed aortic CCR2 mRNA expression, completely reversed macrophage accumulation in the aortic wall, and substantially lowered systolic blood pressure.

Cite This Study

Chan et al. (2012) studied this question.

synapsesocial.com/papers/6a912f8eeb80182e0111fb2e https://doi.org/10.1161/hypertensionaha.112.201251

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Implication

Animal study demonstrates that a CCR2 antagonist reduces vascular macrophage accumulation and blood pressure in hypertensive mice, suggesting chemokine receptor blockade can treat hypertension.

Reversal of Vascular Macrophage Accumulation and Hypertension by a CCR2 Antagonist in Deoxycorticosterone/Salt-Treated Mice

Discussion

Member takes

Implication

Key Points

Cite This Study

Reversal of Vascular Macrophage Accumulation and Hypertension by a CCR2 Antagonist in Deoxycorticosterone/Salt-Treated Mice

Discussion

Member takes

Implication

Key Points

Cite This Study

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